A Study To Evaluate The Efficacy And Safety Of Ifinatamab Deruxtecan (I-DXd) In Subjects With Recurrent Or Metastatic Solid Tumors (IDeate-PanTumor02)

A Phase 1B/2 Pan-Tumor, Open-Label Study To Evaluate The Efficacy And Safety Of Ifinatamab Deruxtecan (I-DXd) In Subjects With Recurrent Or Metastatic Solid Tumors (IDeate-PanTumor02)

This study is designed to assess the efficacy and safety of ifinatamab deruxtecan (I-DXD) in the following tumor types: endometrial cancer (EC); head and neck squamous cell carcinoma (HNSCC); pancreatic ductal adenocarcinoma (PDAC); colorectal cancer (CRC); hepatocellular carcinoma (HCC); adenocarcinoma of esophagus, gastroesophageal junction, and stomach (Ad-Eso/GEJ/gastric); urothelial carcinoma (UC); ovarian cancer (OVC); cervical cancer (CC); biliary tract cancer (BTC); human epidermal growth factor 2 (HER2)-low breast cancer (BC); HER2 immunohistochemistry (IHC) 0 BC; and cutaneous melanoma.

Study Overview

• Status: Recruiting
• Conditions: Recurrent or Metastatic Solid Tumors
• Intervention / Treatment: Drug: Ifinatamab deruxtecan

Detailed Description

This study will evaluate the efficacy and safety of I-DXd in participants with recurrent or metastatic solid tumors previously treated with 1 or more systemic therapies for the selected tumor indication. The study will be divided into 2 parts: Stage 1 and Stage 2. Each cohort starts with Stage 1 and may continue to Stage 2 if sufficient safety and efficacy data are observed.

The HCC Safety Run-In (Phase 1) will assess the safety and tolerability of I-DXd in participants with HCC.

• Study Type: Interventional
• Enrollment (Estimated): 520
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: (US) Daiichi Sankyo Contact for Clinical Trial Information; Phone Number: 9089926400; Email: CTRinfo@dsi.com
• Study Contact Backup: Name: (Asia) Daiichi Sankyo Contact for Clinical Trial Information; Phone Number: +81-3-6225-1111 (M-F 9-5 JST; Email: dsclinicaltrial@daiichisankyo.co.jp

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1118AAT
    • Recruiting
    • Hospital Aleman
    • Contact: Principal Investigator
  • Buenos Aires, Argentina, C1061ABD
    • Not yet recruiting
    • DIABAID
    • Contact: Principal Investigator
  • Caba, Argentina, C1419GEP
    • Recruiting
    • Hospital Sírio Libanês
    • Contact: Principal Investigator
  • Ciudad Autonoma Buenos Aires, Argentina, 1019
    • Recruiting
    • Centro Medico Austral
  • Mar del Plata, Argentina, 7600
    • Recruiting
    • Centro de Investigaciones Médicas Mar del Plata
    • Contact: Principal Investigator
• Australia
  • Blacktown, Australia, NSW 2148
    • Recruiting
    • Blacktown Hospital
  • Mount Kuring-Gai, Australia, 2080
    • Recruiting
    • St Vincent's Hospital Sydney
    • Contact: Principal Investigator
  • Subiaco, Australia, 6008
    • Recruiting
    • St John of God Subiaco Hospital
    • Contact: Principal Investigator
  • Woolloongabba, Australia, 4102
    • Recruiting
    • Princess Alexandra Hospital
    • Contact: Principal Investigator
  • New South Wales
    • St Leonards, New South Wales, Australia, 2065
      • Recruiting
      • Genesiscare North Shore Oncology
      • Contact: Principal Investigator
• Belgium
  • Brussels, Belgium, 1200
    • Recruiting
    • Cliniques Universitaires Saint-Luc
    • Contact: Principal Investigator
  • Charleroi, Belgium, 6000
    • Recruiting
    • Grand hospital de Charleroi
    • Contact: Principal Investigator
  • Ghent, Belgium, 9000
    • Not yet recruiting
    • Universitair Ziekenhuis Gent
    • Contact: Principal Investigator
  • Leuven, Belgium, 3000
    • Recruiting
    • UZ Leuven
    • Contact: Principal Investigator
  • Liège, Belgium, 4000
    • Not yet recruiting
    • Chu de Liă Ge
    • Contact: Principal Investigator
• Brazil
  • Barretos, Brazil, 14784-400
    • Recruiting
    • Hospital de Cancer de Barretos - Fundacao Pio XII
    • Contact: Principal Investigator
  • Florianópolis, Brazil, 88034-000
    • Recruiting
    • Cepon - Centro de Pesquisas Oncolă"Gicas de Santa Catarina
    • Contact: Principal Investigator
  • Jaú, Brazil, 17210-120
    • Recruiting
    • Centro de Pesquisas Clinicas da Fundação Doutor Amaral Carvalho
    • Contact: Principal Investigator
  • Porto Alegre, Brazil, 90035-903
    • Recruiting
    • Hospital de Clinicas de Porto Alegre
    • Contact: Principal Investigator
  • Porto Alegre, Brazil, 90610-000
    • Recruiting
    • Hospital Sao Lucas da PUCRS
    • Contact: Principal Investigator
• Chile
  • Concepción, Chile, 4070196
    • Recruiting
    • Biocenter
    • Contact: Principal Investigator
  • La Serena, Chile, 1720430
    • Not yet recruiting
    • IC La Serena Research
    • Contact: Principal Investigator
  • Santiago, Chile, 8320000
    • Recruiting
    • Centro Del Cancer UC
    • Contact: Principal Investigator
  • Santiago, Chile, 8320000
    • Recruiting
    • Clinica Redsalud Vitacura
    • Contact: Principal Investigator
  • Temuco, Chile, 4800827
    • Not yet recruiting
    • James Lind Centro de Investigacion del Cancer
    • Contact: Principal Investigator
• France
  • Besançon, France, 25000
    • Recruiting
    • CHU Besançon - Hôpital Jean Minjoz
    • Contact: Principal Investigator
  • Bordeaux, France, 33076
    • Recruiting
    • Institut Bergonie
  • Bordeaux, France, 33075
    • Recruiting
    • Hôpital Saint André
  • Dijon, France, 21079
    • Recruiting
    • Centre Georges François Leclerc
    • Contact: Principal Investigator
  • Montpellier, France, 34298
    • Recruiting
    • Institut Régional du Cancer de Montpellier
    • Contact: Principal Investigator
  • Paris, France, 75005
    • Recruiting
    • Institut Curie - Site de Paris
    • Contact: Principal Investigator
  • Rennes, France, 35042
    • Recruiting
    • CRLCC Eugene Marquis
  • Saint-Herblain, France, 44800
    • Recruiting
    • ICO - Site René Gauducheau
    • Contact: Principal Investigator
  • Toulouse, France, 31059
    • Not yet recruiting
    • Institut Claudius Regaud
    • Contact: Principal Investigator
  • Villejuif, France, 94805
    • Recruiting
    • Institut Gustave Roussy
    • Contact: Principal Investigator
  • Rhone
    • Lyon, Rhone, France, 69008
      • Recruiting
      • Centre Leon Berard
      • Contact: Principal Investigator
• Germany
  • Berlin, Germany, 10117
    • Not yet recruiting
    • Charită - Campus Charită Mitte
    • Contact: Principal Investigator
  • Berlin, Germany, 12351
    • Recruiting
    • Vivantes Klinikum Neukoelln
    • Contact: Principal Investigator
  • Dresden, Germany, 01067
    • Recruiting
    • Staedtisches Klinikum Dresden Standort Dresden-Friedrichstadt
    • Contact: Principal Investigator
  • Heidelberg, Germany, 69120
    • Recruiting
    • Universitaetsklinikum Heidelberg
    • Contact: Principal Investigator
  • Heilbronn, Germany, 74078
    • Recruiting
    • SLK-Kliniken Heilbronn GmbH
    • Contact: Principal Investigator
  • Leipzig, Germany, 04103
    • Recruiting
    • Universitäres Krebszentrum Leipzig UCCL, UKL AöR
    • Contact: Principal Investigator
  • Mainz, Germany, 55131
    • Recruiting
    • Univ der Johannes GutenbergU
    • Contact: Principal Investigator
  • Münster, Germany, 48149
    • Recruiting
    • Universitätsklinikum Münster, Medizinische Klinik A
    • Contact: Principal Investigator
• Ireland
  • Cork, Ireland, T12DC4A
    • Not yet recruiting
    • Cork University Hospital
    • Contact: Principal Investigator
  • Dublin, Ireland, D07 R2WY
    • Recruiting
    • Mater Misericordiae University Hospital
    • Contact: Principal Investigator
  • Dublin, Ireland, D24 NR0A
    • Recruiting
    • Tallaght University Hospital
    • Contact: Principal Investigator
  • Dublin, Ireland, DUBLIN 4
    • Recruiting
    • St Vincent's University Hospital
    • Contact: Principal Investigator
  • Galway, Ireland, H91YR71
    • Not yet recruiting
    • University Hospital Galway
    • Contact: Principal Investigator
• Italy
  • Candiolo, Italy, 10060
    • Recruiting
    • Fondazione Del Piemonte Per L'Oncologia Irccs Candiolo
    • Contact: Principal Investigator
  • Milan, Italy, 20133
    • Recruiting
    • Fondazione IRCCS Istituto Nazionale dei Tumori
    • Contact: Principal Investigator
  • Milan, Italy, 20162
    • Recruiting
    • Azienda Socio Sanitaria Territoriale Niguarda (Grande Ospedale Metropolitano Niguarda)
    • Contact: Principal Investigator
  • Napoli, Italy, 80131
    • Recruiting
    • Istituto Nazionale Tumori Fondazione G. Pascale
    • Contact: Principal Investigator
  • Rome, Italy, 00168
    • Recruiting
    • Fondazione Policlinico Universitario Agostino Gemelli IRCCS
    • Contact: Principal Investigator
  • Rozzano, Italy, 20089
    • Recruiting
    • Istituto Clinico Humanitas
    • Contact: Principal Investigator
• Japan
  • Chūōku, Japan, 104-0045
    • Recruiting
    • National Cancer Center Hospital
    • Contact: Principal Investigator
  • Kashiwa, Japan, 277-8577
    • Recruiting
    • National Cancer Center Hospital East
    • Contact: Principal Investigator
  • Kōtoku, Japan, 135-8550
    • Recruiting
    • The Cancer Institute Hospital of JFCR
    • Contact: Principal Investigator
  • Matsuyama, Japan, 791-0280
    • Recruiting
    • National Hospital Organization Shikoku Cancer Center
    • Contact: Principal Investigator
  • Nagaizumi-cho, Japan, 411-8777
    • Recruiting
    • Shizuoka Cancer Center
    • Contact: Principal Investigator
  • Nagoya, Japan, 464-0021
    • Recruiting
    • Aichi Cancer Center Hospital
    • Contact: Principal Investigator
  • Saitama, Japan, 362-0806
    • Recruiting
    • Saitama Cancer Center
    • Contact: Principal Investigator
  • Ōsaka-sayama, Japan, 589-8511
    • Recruiting
    • Kindai University Hospital
    • Contact: Principal Investigator
• Mexico
  • Mérida, Mexico, 97070
    • Not yet recruiting
    • Medical Care & Research SA de CV
    • Contact: Principal Investigator
  • Mérida, Mexico, 97134
    • Not yet recruiting
    • Centro de Atenciă"N E Investigaciă"N Clă Nica En Oncologă A
    • Contact: Principal Investigator
  • México, Mexico, 06100
    • Not yet recruiting
    • Cryptex Investigación Clínica S.A. de C.V.
    • Contact: Principal Investigator
• Netherlands
  • Amsterdam, Netherlands, 1081 HV
    • Recruiting
    • Amsterdam UMC, Locatie VUMC
    • Contact: Principal Investigator
  • Groningen, Netherlands, 9713 GZ
    • Recruiting
    • Universitair Medisch Centrum Groningen
  • Nijmegen, Netherlands, 6525 GA
    • Recruiting
    • Radboudumc Nijmegen
    • Contact: Principal Investigator
  • Rotterdam, Netherlands, 3015 GD
    • Recruiting
    • Erasmus Medisch Centrum
    • Contact: Principal Investigator
  • Rotterdam, Netherlands, 3015 GD
    • Not yet recruiting
    • Erasmus Medisch Centrum
    • Contact: Principal Investigator
  • Utrecht, Netherlands, 3584 CW
    • Recruiting
    • UMC Utrecht
    • Contact: Principal Investigator
• Poland
  • Krakow, Poland, 30-688
    • Recruiting
    • SPZOZ Szpital Uniwer w Krakowie
  • Lodz, Poland, 90-302
    • Recruiting
    • Instytut MSF Sp. z o.o.
  • Rzeszów, Poland, 35-021
    • Recruiting
    • MRUK-MED i Spółka z ograniczoną odpowiedzialnością
    • Contact: Principal Investigator
  • Siedlce, Poland, 08-110
    • Recruiting
    • Mazowiecki Szpital Wojewodzki w Siedlcach Sp z o o
    • Contact: Principal Investigator
  • Skorzewo, Poland, 60-185
    • Recruiting
    • Aidport sp z o.o.
    • Contact: Principal Investigator
• Portugal
  • Lisbon, Portugal, 1400-038
    • Recruiting
    • Fundação Champalimaud
    • Contact: Principal Investigator
  • Lisbon, Portugal, 1649-035
    • Recruiting
    • Centro Hospitalar Universitario de Lisboa Norte
    • Contact: Principal Investigator
  • Lisbon, Portugal, 1099-023
    • Recruiting
    • Instituto Portuguă S de Oncologia de Lisboa Francisco Gentil, Epe
    • Contact: Principal Investigator
  • Porto, Portugal, 4099-001
    • Recruiting
    • Centro Hospitalar Universitário de Santo António
    • Contact: Principal Investigator
  • Porto, Portugal, 4200-072
    • Recruiting
    • Inst Portude Onco do Porto
    • Contact: Principal Investigator
• Spain
  • Barcelona, Spain, 08036
    • Recruiting
    • Hospital Clinic de Barcelona
    • Contact: Principal Investigator
  • Barcelona, Spain, 8035
    • Recruiting
    • Hospital Universitari Vall d'Hebron
    • Contact: Principal Investigator
  • Barcelona, Spain, 08908
    • Recruiting
    • ICO l'Hospitalet - Hospital Duran i Reynals
  • Madrid, Spain, 28041
    • Recruiting
    • Hospital Universitario 12 de Octubre
    • Contact: Principal Investigator
  • Madrid, Spain, 28046
    • Recruiting
    • Hospital Universitario La Paz
    • Contact: Principal Investigator
  • Madrid, Spain, 28040
    • Recruiting
    • Hospital Clinico San Carlos
    • Contact: Principal Investigator
  • Madrid, Spain, 28009
    • Recruiting
    • Hospital General Universitario Gregorio Marañón
    • Contact: Principal Investigator
  • Seville, Spain, 41009
    • Recruiting
    • Hospital Universitario Virgen Macarena
    • Contact: Principal Investigator
• Taiwan
  • Taichung, Taiwan, 404327
    • Recruiting
    • China Medical University Hospital
    • Contact: Principal Investigator
  • Tainan, Taiwan, 70403
    • Recruiting
    • National Cheng Kung University Hospitalx
    • Contact: Principal Investigator
  • Taipei, Taiwan, 10002
    • Recruiting
    • National Taiwan University Hospital
    • Contact: Principal Investigator
  • Taipei, Taiwan, 11217
    • Recruiting
    • Taipei Veterans General Hospital
    • Contact: Principal Investigator
  • Taipei, Taiwan, 11490
    • Recruiting
    • Tri-Service General Hospital
    • Contact: Principal Investigator
  • Taipei, Taiwan, 11259
    • Recruiting
    • Koo Foundation Sun Yat-Sen Cancer Center
• Turkey (Türkiye)
  • Ankara, Turkey (Türkiye), 06010
    • Recruiting
    • Gulhane Training and Research Hospital
    • Contact: Principal Investigator
  • Ankara, Turkey (Türkiye), 06500
    • Recruiting
    • Gazi University Medical Faculty
    • Contact: Principal Investigator
  • Ankara, Turkey (Türkiye), 6590
    • Not yet recruiting
    • Ankara University Cebeci Hospital
    • Contact: Principal Investigator
  • Ankara, Turkey (Türkiye), 6800
    • Not yet recruiting
    • Ankara City Hospital
    • Contact: Principal Investigator
  • Istanbul, Turkey (Türkiye), 34214
    • Recruiting
    • Medipol Mega University Hospital
    • Contact: Principal Investigator
  • Izmir, Turkey (Türkiye), 35530
    • Not yet recruiting
    • Izmir Medicalpark Hospital
    • Contact: Principal Investigator
• United States
  • California
    • Los Angeles, California, United States, 90017
      • Recruiting
      • Los Angeles Cancer Network
      • Contact: Principal Investigator
    • Los Angeles, California, United States, 90067
      • Active, not recruiting
      • Valkyrie Clinical Trials
    • Whittier, California, United States, 90602
      • Recruiting
      • Pih Health Hematology Medical Oncology
      • Contact: Principal Investigator
  • Illinois
    • Skokie, Illinois, United States, 60077
      • Recruiting
      • Orchard Healthcare Research Inc.
      • Contact: Principal Investigator
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • Recruiting
      • M Health Fairview University of Minnesota Medical Center
      • Contact: Principal Investigator
  • New York
    • New York, New York, United States, 10016
      • Recruiting
      • NYU Langone Health
      • Contact: Principal Investigator
    • New York, New York, United States, 10029
      • Recruiting
      • Icahn School of Medicine at Mount Sinai PRIME
      • Contact: Principal Investigator
    • Westbury, New York, United States, 11590
      • Recruiting
      • Clinical Research Alliance
      • Contact: Principal Investigator
  • Tennessee
    • Chattanooga, Tennessee, United States, 37403
      • Recruiting
      • Tn Gynecologic Oncology Group, Llc
      • Contact: Principal Investigator
    • Germantown, Tennessee, United States, 38138
      • Recruiting
      • The West Clinic
      • Contact: Principal Investigator
    • Nashville, Tennessee, United States, 37203
      • Recruiting
      • SCRI Oncology Partners
  • Texas
    • Amarillo, Texas, United States, 79124
      • Recruiting
      • Texas Oncology - West Texas
    • Dallas, Texas, United States, 75246
      • Recruiting
      • Texas Oncology, P.A.
    • Pearland, Texas, United States, 77584
      • Recruiting
      • Texas Oncology Gulf Coast
  • Utah
    • Salt Lake City, Utah, United States, 84108
      • Recruiting
      • University of Utah Hospitals & Clinics
      • Contact: Principal Investigator
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Recruiting
      • Virginia Cancer Specialists
  • Washington
    • Wenatchee, Washington, United States, 98801
      • Recruiting
      • Wenatchee Hospitals and Clinics
      • Contact: Principal Investigator

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Participants must meet all of the following criteria to be included in the study:

Common Inclusion Criteria for All Participants

1. Participant must have at least 1 lesion, not previously irradiated, amenable to core biopsy and must consent to provide a pretreatment biopsy tissue sample. An archival tumor tissue sample obtained within 6 months of consent and after progression during/after treatment with the participant's most recent cancer therapy regimen is also acceptable.
2. Participants ages ≥18 years (follow local regulatory requirements if the legal age of consent for study participation is >18 years).
3. At least 1 measurable lesion on computed tomography (CT) or magnetic resonance imaging (MRI) according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1), as assessed by the investigator.
4. Documentation of radiological disease progression on or after the previous standard-of-care regimen in the advanced/metastatic setting.
5. Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

Additional Inclusion Criteria for EC Participants

1. Pathologically or cytologically documented EC of any histological carcinoma subtype or endometrial carcinosarcoma, irrespective of microsatellite instability or mismatch repair status.
2. Relapse or progression after a platinum-containing systemic treatment and an immune checkpoint inhibitor (ICI)-containing regimen (combined or sequential). Subjects with actionable target tumor mutation should have been previously treated with targeted therapy, with a maximum of 3 prior lines of therapy for endometrial carcinoma or carcinosarcoma. Neoadjuvant/adjuvant therapy may count as 1 line of therapy if the subject progressed within 6 months after completion of therapy.

Additional Inclusion Criteria for HNSCC Participants

1. Pathologically or cytologically documented unresectable or metastatic squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx, excluding nasopharynx, nasal cavity and paranasal sinuses, and unknown primary.
2. Has disease progression after platinum-based and ICI treatment, whether administered in combination or separately. Subjects with actionable target tumor mutation should have been previously treated with targeted therapy, with a maximum of 2 prior therapy lines for unresectable or metastatic HNSCC.
3. Participants without radiographic evidence of major blood vessel invasion/infiltration or tumor demonstrating a >90-degree abutment or encasement of a major blood vessel.
4. Participants with no prior history of Grade ≥3 bleeding as per the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0 within 28 days prior to the start of study drug related to the current head and neck cancer may be included in the study.
5. Documented p16 status for oropharyngeal cancer (historical results are acceptable if available).

Additional Inclusion Criterion for PDAC Participants

1. Pathologically or cytologically documented unresectable or metastatic pancreatic adenocarcinoma that has relapsed or progressed after 1 prior line of gemcitabine-based systemic therapy in the locally advanced/metastatic setting or after 2 lines of therapy if the subject has actionable target tumor mutation and has been previously treated with targeted therapy. No prior treatment with topoisomerase I inhibitors, such as irinotecan or topotecan.

Additional Inclusion Criteria for CRC Participants

1. Pathologically or cytologically documented unresectable or metastatic CRC with microsatellite stable status.

2. Relapse or progression after 1 prior line of systemic therapy including a fluoropyrimidine plus oxaliplatin with or without anti-vascular endothelial growth factor (VEGF) monoclonal antibody (mAb) or anti-epidermal growth factor receptor mAb therapy, as clinically indicated, or relapse or progression after 2 lines of therapy if the subject has received targeted therapy.

   Note: Prior adjuvant/neoadjuvant systemic cytotoxic chemotherapy will count as 1 line of prior systemic therapy if there is documented disease progression during therapy or within 6 months of chemotherapy completion.

3. No prior treatment with topoisomerase I inhibitors, such as irinotecan or topotecan.

Additional Inclusion Criteria for HCC Participants

1. Pathologically or cytologically documented unresectable or metastatic HCC (fibrolamellar and mixed hepatocellular/cholangiocarcinoma subtypes are not eligible) or noninvasive diagnosis of HCC as per the American Association for the Study of Liver Diseases (AASLD) criteria in subjects with a confirmed diagnosis of cirrhosis.
2. Relapse or progression after 1 prior line of an ICI-containing regimen (combination or monotherapy) in the locally advanced/metastatic setting, with a maximum of 2 prior lines. Subjects with actionable target tumor mutation should have been previously treated with targeted therapy.
3. Barcelona Clinic Liver Cancer (BCLC) Stage B or C.
4. Liver function status should be Child-Pugh (CP) Class A.
5. Albumin-Bilirubin (ALBI) Grade 1 within 7 days prior to the first dose of study drug.
6. Participants with large esophageal varices at risk of bleeding must be treated with conventional medical intervention: beta blockers or endoscopic treatment.

Additional Inclusion Criteria for Ad-eso/GEJ/Gastric Participants

1. Pathologically or cytologically documented unresectable or metastatic Ad-eso/GEJ/Gastric that has relapsed or progressed after 1 prior line of systemic therapy in the locally advanced/metastatic setting. Subjects with PD-(L)1+ or MSI-H/dMMR should receive ICI treatment if ICIs are standard of care in the country, unless the subject is ineligible for ICI treatment.
2. If the participant has known history of HER2 positivity (defined by IHC 3+ or IHC 2+ and in situ hybridization [ISH] positive, as classified by American Society of Clinical Oncology - College of American Pathologists [ASCO CAP]) or actionable target, the subject must have been previously treated with a targeted therapy.

Additional Inclusion Criteria for UC Participants

1. Pathologically or cytologically documented unresectable or metastatic UC of the bladder, renal pelvis, ureter, or urethra. Participants with histological variants are allowed if urothelial histology is predominant. Small cell/neuroendocrine tumors are not allowed even if mixed histology.

2. Relapse or progression after at least 1 prior line of ICI-containing systemic therapy, and 1 prior line of systemic chemotherapy, given in combination with other anticancer therapy or separately, with a maximum of 3 prior therapy lines.

   1. At least 1 line of therapy should include enfortumab vedotin in countries where enfortumab vedotin is approved and available.
   2. Perioperative systemic therapies will be counted as 1 line of therapy.
   3. To meet inclusion criteria requirement of prior ICI-containing therapy, use in the perioperative or metastatic setting will suffice.
   4. Subjects with actionable target tumor mutation should have been previously treated with targeted therapy.
   5. The same regimen administered twice in different disease settings will be counted as 1 line of prior therapy.

Additional Inclusion Criteria for CC Participants

1. Histologically confirmed unresectable or metastatic CC that was previously treated with ≥1 prior line of systemic therapy in the locally advanced or metastatic setting. Subjects with actionable target tumor mutation should have been previously treated with targeted therapy.
2. Participants should receive prior anti-programmed death 1/programmed death-ligand 1 treatment and/or tisotumab vedotin if those are standard of care in the country, unless the subject is ineligible for these treatments.

Additional Inclusion Criteria for OVC Participants

1. Histologically confirmed high-grade serous OVC, high-grade endometrioid OVC, primary peritoneal cancer, or fallopian tube cancer that was previously treated with at least 1 line of platinum-based therapy and bevacizumab unless the subject is ineligible for treatment with bevacizumab.
2. Participant is no longer considered eligible for platinum-based therapy per the investigator's opinion or has progressed less than 180 days after the last dose of platinum therapy.
3. Participant is not considered primary platinum refractory and has not progressed during platinum treatment or within 4 weeks after the completion of platinum treatment.
4. Subjects with actionable target tumor mutation should have been previously treated with targeted therapy.

Additional Inclusion Criteria for BTC Participants

1. Pathologically or cytologically documented unresectable or metastatic BTC (intra- or extrahepatic cholangiocarcinoma or gallbladder carcinoma).
2. Relapse or progression after at least 1 prior line of systemic therapy, or 2 prior lines of systemic therapy if the participant has an actionable target and has received targeted therapy.
3. Histological subtypes other than ampullary cancer, small cell cancer, lymphoma, sarcoma, neuroendocrine tumors, mixed tumor histology, and/or mucinous cystic neoplasms (Please note that the histological subtypes listed here are not allowed.)

Additional Inclusion Criteria for HER2-Low BC Participants

1. Pathologically or cytologically documented unresectable or metastatic BC.
2. Low HER2 expression, defined as IHC 2+/ISH- or IHC 1+ (ISH- or untested), according to ASCO-CAP 2018 HER2 testing guidelines, based on most recent testing, regardless of hormonal status.
3. Progression on or after treatment with trastuzumab deruxtecan (T-DXd).
4. Relapse or progression after at least 2 and a maximum of 3 prior lines of systemic therapy. Subjects with metastatic hormone receptor (HR)+ BC who have received endocrine-based therapy and have received at least 2 and a maximum of 3 prior lines of additional systemic therapy in the metastatic setting. Subjects with actionable target tumor mutation should have been previously treated with targeted therapy.

Additional Inclusion Criteria for HER2 IHC 0 BC Participants

1. Pathologically or cytologically documented unresectable or metastatic BC.
2. Negative for HER2 expression, defined as IHC 0 (ISH- or untested) according to ASCO-CAP 2018 HER2 testing guidelines, based on the most recent testing, regardless of hormonal status.
3. Relapse or progression after at least 2 and a maximum of 3 prior lines of systemic therapy. Participants with metastatic HR+ BC who have received endocrine-based therapy and have received at least 2 and a maximum of 3 prior lines of additional systemic therapy in the metastatic setting. Subjects with actionable target tumor mutation should have been previously treated with targeted therapy.

Additional Inclusion Criteria for Cutaneous (Acral and Non-acral) Melanoma Subjects

1. Histologically or cytologically confirmed cutaneous (acral and non-acral) melanoma.
2. Disease progression while on or after having received treatment with ≥1 prior line of ICI based therapy. Prior anti-PD-(L)1 therapy in the adjuvant setting may be counted as 1 line if there is recurrence within 12 weeks of the last dose. If the subject had BRAF mutated melanoma or other actionable target tumor mutation, they must have had disease progression on targeted therapy as well.

Participants who meet any of the following criteria will be disqualified from entering the study:

1. Prior treatment with orlotamab, enoblituzumab, or other B7-homologue 3 (B7-H3)-targeted agents, including I-DXd.
2. Prior discontinuation of an antibody drug conjugate (ADC) that consists of an exatecan derivative (eg, T-DXd) due to treatment-related toxicities.
3. Clinically active brain metastases, spinal cord compression, or leptomeningeal carcinomatosis, defined as untreated or symptomatic, or requiring therapy with steroids or anticonvulsants to control associated symptoms.
4. Inadequate treatment washout period before enrollment as specified in the protocol.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

13

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1: Endometrial Cancer; Participants with recurrent or metastatic endometrial cancer who were previously treated with 1 or more systemic therapy who received an intravenous infusion of I-DXd 12 mg/kg.	Drug: Ifinatamab deruxtecan; Intravenous administration; Other Names: I-DXd
Experimental: Cohort 2: Head and Neck Squamous Cell Carcinoma; Participants with recurrent or metastatic head and neck squamous carcinoma who were previously treated with 1 or more systemic therapy who received an intravenous infusion of I-DXd 12 mg/kg.	Drug: Ifinatamab deruxtecan; Intravenous administration; Other Names: I-DXd
Experimental: Cohort 3: Pancreatic Ductal Adenocarcinoma; Participants with recurrent or metastatic pancreatic ductal adenocarcinoma who were previously treated with 1 or more systemic therapy who received an intravenous infusion of I-DXd 12 mg/kg.	Drug: Ifinatamab deruxtecan; Intravenous administration; Other Names: I-DXd
Experimental: Cohort 4: Colorectal Cancer; Participants with recurrent or metastatic colorectal cancer who were previously treated with 1 or more systemic therapy who received an intravenous infusion of I-DXd 12 mg/kg.	Drug: Ifinatamab deruxtecan; Intravenous administration; Other Names: I-DXd
Experimental: Cohort 6: Adenocarcinoma of esophagus, gastroesophageal junction, and stomach; Participants with recurrent or metastatic adenocarcinoma of esophagus, gastroesophageal junction, and stomach who were previously treated with 1 or more systemic therapy who received an intravenous infusion of I-DXd 12 mg/kg.	Drug: Ifinatamab deruxtecan; Intravenous administration; Other Names: I-DXd
Experimental: Cohort 5: Hepatocellular Carcinoma; Participants with recurrent or metastatic hepatocellular carcinoma who were previously treated with 1 or more systemic therapy who received an intravenous infusion of I-DXd at the determined dose.	Drug: Ifinatamab deruxtecan; Intravenous administration; Other Names: I-DXd
Experimental: Cohort 7: Urothelial carcinoma; Participants with recurrent or metastatic urothelial carcinoma who were previously treated with 1 or more systemic therapy who received an intravenous infusion of I-DXd 12 mg/kg.	Drug: Ifinatamab deruxtecan; Intravenous administration; Other Names: I-DXd
Experimental: Cohort 8: Ovarian cancer; Participants with recurrent or metastatic non-squamous ovarian cancer who were previously treated with 1 or more systemic therapy who received an intravenous infusion of I-DXd 12 mg/kg.	Drug: Ifinatamab deruxtecan; Intravenous administration; Other Names: I-DXd
Experimental: Cohort 9: Cervical cancer; Participants with recurrent or metastatic cervical cancer who were previously treated with 1 or more systemic therapy who received an intravenous infusion of I-DXd 12 mg/kg.	Drug: Ifinatamab deruxtecan; Intravenous administration; Other Names: I-DXd
Experimental: Cohort 10: Biliary tract cancer; Participants with recurrent or metastatic biliary tract cancer who were previously treated with 1 or more systemic therapy who received an intravenous infusion of I-DXd 12 mg/kg.	Drug: Ifinatamab deruxtecan; Intravenous administration; Other Names: I-DXd
Experimental: Cohort 11: Human epidermal growth factor 2 (HER2)-low breast cancer; Participants with recurrent or metastatic human epidermal growth factor 2 (HER2)-low breast cancer who were previously treated with 1 or more systemic therapy who received an intravenous infusion of I-DXd 12 mg/kg.	Drug: Ifinatamab deruxtecan; Intravenous administration; Other Names: I-DXd
Experimental: Cohort 12: HER2 immunohistochemistry (IHC) 0 breast cancer; Participants with recurrent or metastatic HER2 immunohistochemistry (IHC) 0 breast cancer who were previously treated with 1 or more systemic therapy who received an intravenous infusion of I-DXd 12 mg/kg.	Drug: Ifinatamab deruxtecan; Intravenous administration; Other Names: I-DXd
Experimental: Cohort 13: Cutaneous melanoma; Participants with recurrent or metastatic cutaneous melanoma who were previously treated with 1 or more systemic therapy who received an intravenous infusion of I-DXd 12 mg/kg.	Drug: Ifinatamab deruxtecan; Intravenous administration; Other Names: I-DXd

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR) as Assessed by Investigator	ORR is defined as the proportion of participants with a best overall response (BOR) of confirmed complete response (CR) or confirmed partial response (PR) as assessed by Investigator per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.	From the time of the first dose of study drug until the date of documented disease progression, death, loss to follow-up, or withdrawal by the subject, whichever occurs first up to approximately 57 months
Number of Participants Reporting Dose-limiting Toxicities in the HCC Cohort	A dose-limiting toxicity (DLT) is defined as any treatment-emergent adverse event (TEAE) not attributable to disease or disease-related processes that occurs during the DLT evaluation period (from C1D1 to the end of Cycle 1 in Safety Run-in) and is Grade 3 or above, according to NCI-CTCAE version 5.0, with the exceptions as noted in the protocol.	Cycle 1 Day 1 to Cycle 1 Day 21
Number of Participants Reporting Treatment-emergent Adverse Events and Death in the HCC Cohort	A TEAE is defined as an adverse event (AE) with a start or worsening date during the on-treatment period. AEs will be coded using MedDRA and will be graded using NCI-CTCAE v5.0.	From date of signing the informed consent form up to 47 days after the last dose of study drug , up to approximately 57 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Adverse Events of Special Interest (AESIs)	A TEAE is defined as an adverse event (AE) with a start or worsening date during the on-treatment period. A serious AE is defined as any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, is an important medical event, or may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes noted. AESIs will also be assessed. AEs will be coded using MedDRA and will be graded using NCI-CTCAE v5.0.	From date of signing the informed consent form up to 47 days after the last dose of study drug , up to approximately 57 months
Duration of Response (DoR)	DoR is defined as the time from the first documented confirmed response (CR or PR) to the date of progression or death due to any cause as assessed by Investigator per RECIST v1.1, respectively. CR was defined as a disappearance of all target and non-target lesions and PR was defined as at least a 30% decrease in the sum of diameters of target lesions.	From the time of the first dose of study drug until the date of documented disease progression (confirmed by investigator), death, loss to follow-up, or withdrawal by the subject, whichever occurs first, up to approximately 57 months
Progression-free Survival (PFS)	PFS is defined as the time from the start of study treatment to the earlier of the dates of the first documentation of objective progressive disease (PD) per RECIST v1.1 or death due to any cause. PFS will be determined by the Investigator.	From the time of the first dose of study drug until the date of documented disease progression, death, loss to follow-up, or withdrawal by the subject, whichever occurs first, up to approximately 57 months
Disease Control Rate (DCR)	DCR is defined as the proportion of participants who achieved a BOR of confirmed CR, confirmed PR, or stable disease (SD) as assessed by the Investigator per RECIST v1.1, respectively. CR was defined as a disappearance of all target and non-target lesions, PR was defined as at least a 30% decrease in the sum of diameters of target lesions, and stable disease (SD) was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD; at least a 20% increase in the sum of diameters of target lesions.	From the time of the first dose of study drug until the date of documented disease progression (by investigator), death, loss to follow-up, or withdrawal by the subject, whichever occurs first, up to approximately 57 months
Overall Survival (OS)	OS is defined as the time interval from the date of the first dose of study drug to the date of death from any cause.	From the date of the first dose of drug up to the date of death due to any cause, up to approximately 57 months
Pharmacokinetic Parameter Maximum Concentration (CMax) for I DXd, total anti-B7-H3 antibody, and DXd	Plasma pharmacokinetic parameters will be estimated using noncompartmental methods.	Cycles 1 and 3 Day 1: predose, end of infusion, 3 hours (hr), 6 hr; 24 hr, 168 hr; 336 hr; 504 hr; Cycles 2, 4, and 5 Day 1: predose and end of infusion; Cycle 7 and every 2 cycles thereafter up to EOS (57 months) predose (every cycle is 21 days)
Pharmacokinetic Parameter Time to Reach Maximum Plasma Concentration (TMax) for I DXd, total anti-B7-H3 antibody, and DXd	Plasma pharmacokinetic parameters will be estimated using noncompartmental methods.	Cycles 1 and 3 Day 1: predose, end of infusion, 3 hours (hr), 6 hr; 24 hr, 168 hr; 336 hr; 504 hr; Cycles 2, 4, and 5 Day 1: predose and end of infusion; Cycle 7 and every 2 cycles thereafter up to EOS (57 months) predose (every cycle is 21 days)
Pharmacokinetic Parameter Half-life (t1/2) for I DXd, total anti-B7-H3 antibody, and DXd	Plasma pharmacokinetic parameters will be estimated using noncompartmental methods.	Cycles 1 and 3 Day 1: predose, end of infusion, 3 hours (hr), 6 hr; 24 hr, 168 hr; 336 hr; 504 hr; Cycles 2, 4, and 5 Day 1: predose and end of infusion; Cycle 7 and every 2 cycles thereafter up to EOS (57 months) predose (every cycle is 21 days)
Pharmacokinetic Parameter Minimum Concentration (Ctrough) for I DXd, total anti-B7-H3 antibody, and DXd	Plasma pharmacokinetic parameters will be estimated using noncompartmental methods.	Cycles 1 and 3 Day 1: predose, end of infusion, 3 hours (hr), 6 hr; 24 hr, 168 hr; 336 hr; 504 hr; Cycles 2, 4, and 5 Day 1: predose and end of infusion; Cycle 7 and every 2 cycles thereafter up to EOS (57 months) predose (every cycle is 21 days)
Pharmacokinetic Parameter Area Under the Curve (AUC) for I DXd, total anti-B7-H3 antibody, and DXd	Plasma pharmacokinetic parameters will be estimated using noncompartmental methods.	Cycles 1 and 3 Day 1: predose, end of infusion, 3 hours (hr), 6 hr; 24 hr, 168 hr; 336 hr; 504 hr; Cycles 2, 4, and 5 Day 1: predose and end of infusion; Cycle 7 and every 2 cycles thereafter up to EOS (57 months) predose (every cycle is 21 days)
Percentage of Participants Who Are Anti-Drug Antibody (ADA)-Positive (Baseline and Post-Baseline)	Anti-drug antibodies will be measured in the plasma using a validated assay.	Baseline up to 57 months
Percentage of Participants Who Have Treatment-emergent ADA	Anti-drug antibodies will be measured in the plasma using a validated assay.	Baseline up to 57 months

Collaborators and Investigators

• Sponsor: Daiichi Sankyo
• Collaborators: Merck Sharp & Dohme LLC

Study record dates

Study Major Dates

• Study Start (Actual): April 10, 2024
• Primary Completion (Estimated): July 25, 2028
• Study Completion (Estimated): July 25, 2028

Study Registration Dates

• First Submitted: March 19, 2024
• First Submitted That Met QC Criteria: March 19, 2024
• First Posted (Actual): March 26, 2024

Study Record Updates

• Last Update Posted (Actual): February 12, 2026
• Last Update Submitted That Met QC Criteria: February 10, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Colorectal cancer; Ovarian cancer; Hepatocellular carcinoma; Pancreatic ductal adenocarcinoma; Cervical cancer; Endometrial cancer; Urothelial carcinoma; Head and neck squamous cell carcinoma; Biliary tract cancer; Cutaneous melanoma; Recurrent or metastatic solid tumors; Adenocarcinoma of esophagus, gastroesophageal junction, and stomach; Ifinatamab deruxtecan (I-DXD); DS7300a; Human epidermal growth factor 2 (HER2)-low breast cancer; HER2 immunohistochemistry 0 breast cancer
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Endocrine System Diseases; Pathologic Processes; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Disease Attributes; Intestinal Diseases; Neoplasms by Histologic Type; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Uterine Diseases; Genital Diseases, Female; Endocrine Gland Neoplasms; Head and Neck Neoplasms; Biliary Tract Diseases; Liver Diseases; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Liver Neoplasms; Colonic Diseases; Ovarian Diseases; Adnexal Diseases; Genital Neoplasms, Female; Gonadal Disorders; Skin Diseases; Carcinoma; Uterine Cervical Diseases; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Uterine Neoplasms; Neuroendocrine Tumors; Nevi and Melanomas; Skin Neoplasms; Carcinoma, Squamous Cell; Pathological Conditions, Signs and Symptoms; Skin and Connective Tissue Diseases; Squamous Cell Carcinoma of Head and Neck; Biliary Tract Neoplasms; Recurrence; Carcinoma, Hepatocellular; Colorectal Neoplasms; Ovarian Neoplasms; Uterine Cervical Neoplasms; Melanoma; Endometrial Neoplasms; Carcinoma, Transitional Cell; Adenocarcinoma Of Esophagus
• Other Study ID Numbers: DS7300-203; JRCT2031240016 (Other Identifier: JRCT); 2023-509632-26-00 (Other Identifier: EU CTR)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual participant data (IPD) on completed studies and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/
• IPD Sharing Time Frame: Completed studies that has reached a global end or completion with all data set collected and analyzed, and for which the medicine and indication have received European Union (EU) and United States (US), and/or Japan (JP) marketing approval on or after 01 January 2014 or by the US or EU or JP Health Authorities when regulatory submissions in all regions are not planned and after the primary study results have been accepted for publication.
• IPD Sharing Access Criteria: Formal request from qualified scientific and medical researchers on IPD and clinical study documents on completed clinical trials supporting products submitted and licensed in the United States, the European Union and/or Japan from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No