GEN1042 Safety Trial and Anti-tumor Activity in Subjects With Malignant Solid Tumors

A First-in-Human, Open-label, Dose-escalation Trial With Expansion Cohorts to Evaluate Safety and Anti-tumor Activity of GEN1042 in Subjects With Malignant Solid Tumors

To evaluate the safety and anti-tumor activity of GEN1042 in patients with metastatic or locally advanced solid tumors.

Study Overview

• Status: Recruiting
• Conditions: Melanoma; Malignant Solid Tumor; Non Small Cell Lung Cancer (NSCLC); Pancreatic Ductal Adenocarcinoma (PDAC); Head and Neck Squamous Cell Carcinoma (HNSCC); Colorectal Cancer (CRC)
• Intervention / Treatment: Drug: Carboplatin; Drug: Paclitaxel; Drug: Cisplatin; Drug: Gemcitabine; Drug: Pembrolizumab; Drug: Pemetrexed; Biological: GEN1042; Drug: 5-FU; Drug: Nab paclitaxel

Detailed Description

This is an open-label, multicenter phase 1/2 study designed to assess the safety, pharmacokinetics, pharmacodynamics and anti-tumor activity of GEN1042 administered as a monotherapy or in combination in subjects with metastatic or locally advanced solid tumors.

• Study Type: Interventional
• Enrollment (Estimated): 1287
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Genmab A/S Trial Information; Phone Number: +4570202728; Email: clinicaltrials@genmab.com

Study Locations

• Denmark
  • Copenhagen, Denmark
    • Completed
    • Rigshospitalet (Copenhagen University Hospital)
  • Herlev, Denmark
    • Recruiting
    • Herlev University Hospital
  • Vejle, Denmark
    • Recruiting
    • University Hospital of Southern Denmark, Vejle Hospital
• France
  • Bordeaux, France
    • Recruiting
    • Centre hospitalier Universitaire de Bordeaux
  • Nice, France
    • Not yet recruiting
    • Centre Antoine Lacassagne
  • Villejuif, France
    • Recruiting
    • Gustave Roussy
• Georgia
  • Tbilisi, Georgia
    • Recruiting
    • ARENSIA Research Clinic at the Research Institute of Clinical Medicine
• Germany
  • Heidelberg, Germany
    • Completed
    • Nationales Centrum fr Tumorerkrankungen NCT
  • Ludwigshafen, Germany
    • Completed
    • Klinikum der Stadt Ludwigshafen am Rhein gGmbH
  • Mainz, Germany
    • Completed
    • Department of Dermatology, University of Mainz
  • Mannheim, Germany
    • Completed
    • Universitätsmedizin Mannheim Dermatologie
  • Wuerzburg, Germany
    • Completed
    • Universitaetsklinikum Wuerzburg
• Israel
  • Petah tikva, Israel
    • Recruiting
    • Rabin Medical Center
  • Tel Aviv, Israel
    • Recruiting
    • Tel Aviv Sourasky Medical Center
• Italy
  • Brescia, Italy
    • Recruiting
    • Azienda Ospedaliera Spedali Civili di Brescia
  • Cuneo, Italy
    • Recruiting
    • Azienda Ospedaliera S.Croce e Carle Cuneo
  • Milan, Italy
    • Recruiting
    • Istituto Nazionale dei Tumori
  • Rozzano, Italy
    • Recruiting
    • Istituto Clinico Humanitas
• Korea, Republic of
  • Cheongju-si, Korea, Republic of
    • Recruiting
    • Chungbuk National University Hospital
  • Jeonju, Korea, Republic of
    • Recruiting
    • Jeonbuk national university hospital
  • Namdong, Korea, Republic of
    • Recruiting
    • Gachon University Gil Medical Center
  • Seoul, Korea, Republic of
    • Recruiting
    • Samsung Medical Center
  • Seoul, Korea, Republic of
    • Recruiting
    • Korea University Guro Hospital
  • Seoul, Korea, Republic of
    • Recruiting
    • Severance Hospital, Yonsei University Health System
  • Yangsan, Korea, Republic of
    • Recruiting
    • Pusan National University Yangsan Hospital
• Moldova, Republic of
  • Chisinau, Moldova, Republic of
    • Recruiting
    • ARENSIA Research Clinic at the Oncology Institute
• Spain
  • Barcelona, Spain
    • Recruiting
    • H. Vall d'Hebron
    • Contact: E Felip
  • Barcelona, Spain
    • Recruiting
    • START Barcelona HM Nou Delfos
  • L'Hospitalet De Llobregat, Spain
    • Recruiting
    • Hospital Duran i Reynals - ICO L Hospitalet
  • Las Palmas De Gran Canaria, Spain, 35016
    • Recruiting
    • Hospital Universitario Insular de Gran Canaria
  • Lugo, Spain
    • Recruiting
    • Hospital Universitario Lucus Augusti
  • Madrid, Spain
    • Recruiting
    • Clinica Universidad de Navarra
  • Madrid, Spain
    • Recruiting
    • Hospital Universitario 12 de Octubre
  • Madrid, Spain
    • Recruiting
    • Hospital Universitario La Paz
  • Madrid, Spain
    • Recruiting
    • Hospital Universitario Ramon y Cajal
  • Madrid, Spain
    • Recruiting
    • Hospital Clinico San Carlos
  • Madrid, Spain
    • Recruiting
    • HM CIOCC Hospital Universitario HM Sanchinarro
    • Contact: M De Miguel Luken
  • Madrid, Spain
    • Recruiting
    • MD Anderson Cancer Center Madrid
    • Contact: E Grande
  • Madrid, Spain
    • Recruiting
    • START Madrid - Hospital Universitario Fundacion Jimenez Diaz
    • Contact: V Moreno
  • Madrid, Spain
    • Recruiting
    • Hospital General Universitario Gregorio Maran
  • Málaga, Spain
    • Recruiting
    • Hospital Universitario Virgen de la Victoria
  • Pamplona, Spain
    • Recruiting
    • Clinica Universidad de Navarra
    • Contact: I Melero
  • Santiago De Compostela, Spain
    • Recruiting
    • Complejo Hospitalario Universitario de Santiago (CHUS)
  • Sevilla, Spain
    • Recruiting
    • Hospital Virgen del Rocío
  • Valencia, Spain
    • Recruiting
    • Hospital Clinico Universitario de Valencia
• Taiwan
  • Kaohsiung City, Taiwan
    • Recruiting
    • Chang Gung Memorial Hospital (CGMH) - Kaohsiung Branch
  • Kaohsiung City, Taiwan
    • Recruiting
    • Kaohsiung Medical University Memorial Hospital
  • Taichung, Taiwan
    • Recruiting
    • China Medical University Hospital
  • Tainan, Taiwan
    • Recruiting
    • National Cheng Kung University Hospital
  • Taipei, Taiwan
    • Recruiting
    • Taipei Medical University Hospital
  • Taipei, Taiwan
    • Recruiting
    • Taipei Veterans General Hospital, VGHTPE
  • Taoyuan, Taiwan
    • Recruiting
    • Chang Gung Memorial Hospital Linkou Branch
• United Kingdom
  • Sutton, United Kingdom
    • Completed
    • Royal Marsden NHS Foundation Trust
• United States
  • Alaska
    • Anchorage, Alaska, United States, 99508
      • Recruiting
      • Alaska Oncology and Hematology LLC
  • California
    • Los Alamitos, California, United States, 90720
      • Recruiting
      • Cancer & Blood Specialty Clinic
    • San Diego, California, United States, 92037
      • Recruiting
      • Moores Cancer Center at the UC San Diego Health
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Recruiting
      • Yale University Cancer Center
      • Principal Investigator: Patricia LoRusso
  • Delaware
    • Newark, Delaware, United States, 19713
      • Recruiting
      • ChristianaCare
  • Florida
    • Miami Beach, Florida, United States, 33140
      • Recruiting
      • Mount Sinai Comprehensive Cancer Center
    • Ocala, Florida, United States, 34474
      • Recruiting
      • Florida Cancer Affiliates
  • Illinois
    • Hinsdale, Illinois, United States, 60521
      • Recruiting
      • Hope and Healing Cancer Services
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • Recruiting
      • University of Kentucky
    • Louisville, Kentucky, United States, 40202
      • Recruiting
      • Norton Cancer Institute
  • Maryland
    • Columbia, Maryland, United States, 21044
      • Recruiting
      • Maryland Oncology Hematology PA
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Recruiting
      • Washington University School of Medicine
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Recruiting
      • Levine Cancer Center
      • Principal Investigator: Daniel Haggstrom
    • Winston-Salem, North Carolina, United States, 27103
      • Recruiting
      • Novant Health Cancer Institute - Forsyth (Medical Oncology)
  • Oregon
    • Portland, Oregon, United States, 97227
      • Recruiting
      • Kaiser Permanente (KP) Oncology/Hematology
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Recruiting
      • University of Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19111
      • Recruiting
      • Fox Chase Cancer Center
      • Principal Investigator: Crystal Denlinger
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Recruiting
      • Sarah Cannon Research Institute
      • Contact: cann.researchreferrals@scresearch.net
      • Principal Investigator: Melissa Johnson
  • Texas
    • Kingwood, Texas, United States, 77339
      • Recruiting
      • Lumi Research
  • Utah
    • Salt Lake City, Utah, United States, 84124
      • Recruiting
      • Utah Cancer Specialists
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Recruiting
      • Virgina Cancer Specialists
  • Washington
    • Seattle, Washington, United States, 98109
      • Recruiting
      • Adventist Health System/Sunbelt,Inc
    • Spokane, Washington, United States, 99204
      • Recruiting
      • Medical Oncology Associates, PS

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

Monotherapy - Dose Escalation and Dose Expansion Parts

• Subjects with non-CNS solid tumors that is metastatic or unresectable and for whom there is no available standard therapy.
• Subjects with a confirmed diagnosis of relapsed or refractory, advanced and/or metastatic melanoma, NSCLC, or CRC and for whom there is no available standard therapy

Combination Therapy - Dose Expansion Part

• Subjects with unresectable Stage III or Stage IV melanoma with no prior systemic anticancer therapy for unresectable or metastatic disease. Primary ocular or mucosal melanoma is excluded.
• Subjects with Stage IV metastatic or recurrent NSCLC with no prior systemic anticancer therapy, no actionable mutation.
• Subjects with recurrent or metastatic HNSCC with no prior systemic therapy administered in the recurrent or metastatic setting.
• Subjects with confirmed metastatic PDAC with no previous radiotherapy, surgery, chemotherapy, or investigational therapy for the treatment of metastatic disease.

General (all phases):

• Must be age ≥ 18 years of age on the day of signing informed consent, or the legal age of consent in the jurisdiction in which the trial is taking place.
• Measurable disease according to RECIST 1.1
• Eastern Cooperative Oncology Group (ECOG) 0-1
• Normal or adequate liver, renal, cardiac and bone marrow function

Key Exclusion Criteria:

Monotherapy - Dose Escalation and Dose Expansion Parts

• Treatment with an anti-cancer agent (within 21 days or after at least 5 half-lives of the drug, whichever is shorter), prior to GEN1042 administration
• Radiotherapy within 14 days prior to first GEN1042 administration
• Toxicities from previous anti-cancer therapies that have not resolved

Combination Therapy - Dose Expansion Part

• Has received prior systemic cytotoxic chemotherapy, biological therapy, OR major surgery within 3 weeks or at least 5 half-lives of the drug (whichever is shorter) of the first dose of trial treatment.
• Radiotherapy within 14 days of start of trial treatment or received lung radiation therapy of > 30 Gy within 6 months of the first dose of trial treatment.

General (all phases)

• Subject has an active, known, or suspected autoimmune disease.
• History of non-infectious pneumonitis that required steroids or currently has pneumonitis.
• History of ≥ grade 3 allergic reactions to monoclonal antibody (mAb) therapy
• Subject with a condition requiring systemic treatment with either corticosteroids (>10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of first treatment.

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Monotherapy - Dose Escalation and Dose Expansion parts; Escalating doses of GEN1042 monotherapy in subjects with non-central nervous system (CNS) solid malignant tumors followed by monotherapy expansion cohorts at selected dose(s) in subjects with relapsed or refractory, advanced and/or metastatic melanoma, or non-small-cell lung cancer (NSCLC), or colorectal cancer (CRC).	Biological: GEN1042; Intravenous
Experimental: Combination Therapy - Dose Expansion Part; GEN1042 safety and efficacy will be evaluated in combination with pembrolizumab with or without chemotherapy in treatment-naive subjects with advanced or metastatic melanoma, non-small-cell lung cancer [NSCLC], head and neck squamous cell carcinoma [HNSCC], and pancreatic cancer.	Drug: Carboplatin; Intravenous; Drug: Paclitaxel; Intravenous; Drug: Cisplatin; Intravenous; Drug: Gemcitabine; Intravenous; Drug: Pembrolizumab; Intravenous; Drug: Pemetrexed; Intravenous; Biological: GEN1042; Intravenous; Drug: 5-FU; Intravenous; Drug: Nab paclitaxel; Intravenous

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Subjects With Dose-Limiting Toxicities (DLT)	Occurrence of Dose-Limiting Toxicities (DLT) assessed by the Investigator	First Cycle (21 days)
Objective Response Rate (ORR)	Defined as proportion of participants who have a confirmed partial or complete response (PR or CR). Determined by the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.	From the start of the study treatment until disease progression/death/ lost to follow-up/start of new anticancer therapy or withdrawal of consent, whichever occurs first. (an expected average of 10 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose Escalation: Area Under the Concentration Time Curve (AUC) of GEN1042	Pharmacokinetic (PK) parameters of GEN1042, and incidence of anti-drug antibodies Dose Escalation: Area Under the Concentration Time Curve (AUC) of GEN1042	Cycle (Cy) 1 Day (D) 1 before GEN1042 infusion (BI) and , End of GEN1042 Infusion (EOI), Cy1 D2, 3, 8, 15, Cy2 BI, EOI on D1, D 2, 3, 8, 15, and then D1 of Cy 3, 5, 7, 11, 15 and every 4 cycles thereafter (up to end of treatment) (Cy =21 days)
Dose Escalation: Maximum Concentration (Cmax) of GEN1042	Pharmacokinetic (PK) parameters of GEN1042, and incidence of anti-drug antibodies Dose Escalation: Maximum Concentration (Cmax) of GEN1042	Cycle (Cy) 1 Day (D) 1 before GEN1042 infusion (BI) and End of Infusion (EOI), Cy1 D2, 3, 8, 15, Cy2 BI, EOI on D1, D 2, 3, 8, 15, and then D1 of Cy 3, 5, 7, 11, 15 and every 4 cycles thereafter (up to end of treatment) (Cy =21 days)
Dose Escalation: Half-life (t1/2) of GEN1042	Dose Escalation: Half-life (t1/2) of GEN1042	Cycle (Cy) 1 Day (D) 1 before GEN1042 infusion (BI) and End of Infusion (EOI), Cy1 D2, 3, 8, 15, Cy2 BI, EOI on D1, D 2, 3, 8, 15, and then D1 of Cy 3, 5, 7, 11, 15 and every 4 cycles thereafter (up to end of treatment) (Cy =21 days)
Dose Expansion: Area Under the Concentration Time Curve (AUC) of GEN1042	Dose Expansion: Area Under the Concentration Time Curve (AUC) of GEN1042	Cy 1 BI, EOI on D1, D8, 15, Cy 2 BI, EOI on D1, D8, 15, and then D1 of Cy 3, 5, 7, 11, 15 and every 4 cycles thereafter (up to end of treatment) (Cy =21 days)
Dose Expansion: Maximum Concentration (Cmax) of GEN1042	Dose Expansion: Maximum Concentration (Cmax) of GEN1042	Cy 1 BI, EOI on D1, D8, 15, Cy 2 BI, EOI on D1, D8, 15, and then D1 of Cy 3, 5, 7, 11, 15 and every 4 cycles thereafter (up to end of treatment) (Cy =21 days)
Percentage of Subjects with Adverse Events and Serious Adverse Events	Incidence of Adverse Events and Serious Adverse Events as assessed by NCI CTCAE V5.0	Baseline up to 90 Days After the Last Dose, assessed up to 36 months after the last subject's first treatment in the trial.
Duration of Object Response (DOR)	Defined as time from the first documentation of objective response (CR or PR) to the date of first PD or death.	From the start of the study treatment until disease progression/death/ lost to follow-up/start of new anticancer therapy or withdrawal of consent, whichever occurs first. (an expected average of 10 months)
Disease Control Rate (DCR)	Determined by Investigator Using RECIST Version 1.1	From the start of the study treatment until disease progression/death/ lost to follow-up/start of new anticancer therapy or withdrawal of consent, whichever occurs first. (an expected average of 10 months)
Progression-Free Survival (PFS)	Defined as the time from start of study treatment to first documented progression per RECIST Version 1.1 by investigator assessment or death due to any cause, whichever occurs first.	From the start of the study treatment until disease progression/death whichever occurs first. (an expected average of 10 months)
Overall survival (OS)	Defined as the time from start of study treatment to date of death due to any cause.	From the start of the study treatment until death due to any cause, assessed up to 36 months after the last subject's first treatment in the trial.
Dose Escalation: Incidence of ADA response to GEN1042	Dose Escalation: Incidence of ADA response to GEN1042responses to GEN1042	BI on Cy 1, 2, 3, 5, 7, 11, 15 and every 4 cycles thereafter (up to end of treatment), safety follow-up visit (SFU) (30 and 90 days post final dose) (Cy =21 days)
Dose Expansion: Incidence of ADA response to GEN1042	Dose Expansion: Incidence of ADA response to GEN1042	BI on Cy 1, 2, 3, 5, 7, 11, 15 and every 4 cycles thereafter (up to end of treatment), SFU (30 and 90 days post final dose) (Cy =21 days)

Collaborators and Investigators

• Sponsor: Genmab
• Collaborators: BioNTech SE

Publications and helpful links

General Publications

• Muik A, Adams 3rd HC, Gieseke F, Altintas I, Schoedel KB, Blum JM, Sanger B, Burm SM, Stanganello E, Verzijl D, Spires VM, Vascotto F, Toker A, Quinkhardt J, Fereshteh M, Diken M, Satijn DPE, Kreiter S, Ahmadi T, Breij ECW, Tureci O, Sasser K, Sahin U, Jure-Kunkel M. DuoBody-CD40x4-1BB induces dendritic-cell maturation and enhances T-cell activation through conditional CD40 and 4-1BB agonist activity. J Immunother Cancer. 2022 Jun;10(6):e004322. doi: 10.1136/jitc-2021-004322. Erratum In: J Immunother Cancer. 2022 Sep;10(9):

Study record dates

Study Major Dates

• Study Start (Actual): September 17, 2019
• Primary Completion (Estimated): July 1, 2025
• Study Completion (Estimated): October 1, 2025

Study Registration Dates

• First Submitted: September 6, 2019
• First Submitted That Met QC Criteria: September 6, 2019
• First Posted (Actual): September 10, 2019

Study Record Updates

• Last Update Posted (Actual): May 7, 2024
• Last Update Submitted That Met QC Criteria: May 6, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Head and Neck Neoplasms; Carcinoma, Squamous Cell; Neoplasms; Squamous Cell Carcinoma of Head and Neck; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Folic Acid Antagonists; Carboplatin; Paclitaxel; Pembrolizumab; Albumin-Bound Paclitaxel; Pemetrexed; Gemcitabine
• Other Study ID Numbers: GCT1042-01; 2018-003716-47 (EudraCT Number); IRAS ID: 263292 (Registry Identifier: UK Research Summaries Database); MOH_2023-07-31_012855 (Registry Identifier: Israel MyTrials); 2023-508526-10-00 (Ctis: EU CT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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