Study to Evaluate Adverse Events, Change in Disease Activity, and How ABBV-706 Moves Through the Body When Intravenously (IV) Infused Alone or in Combination With IV Infused Budigalimab, Cisplatin, or Carboplatin in Adult Participants With Advanced Solid Tumors

A Phase 1 First-in-Human Study Evaluating Safety, Pharmacokinetics and Efficacy of ABBV-706 as Monotherapy and in Combination With Budigalimab (ABBV-181), Carboplatin, or Cisplatin in Adult Subjects With Advanced Solid Tumors

Cancer is a condition where cells in a specific part of body grow and reproduce uncontrollably. The purpose of this study is to assess safety, tolerability, pharmacokinetics and preliminary efficacy of ABBV-706 as a monotherapy and in combination with budigalimab, carboplatin, or cisplatin.

ABBV-706 is an investigational drug being developed for the treatment of small cell lung cancer (SCLC), high-grade central nervous system (CNS) tumors and high-grade neuroendocrine carcinomas (NECs). There are multiple treatment arms in this study. Participants will either receive ABBV-706 as a single agent or in combination with budigalimab (another investigational drug), carboplatin or cisplatin at different doses. Approximately 350 adult participants will be enrolled in the study across sites worldwide.

In part 1 (dose escalation), ABBV-706 will be intravenously infused in escalating doses as a monotherapy until the maximum tolerated dose (MTD) is determined in participants with SCLC, high-grade CNS tumors, and high-grade NECs. In part 2, multiple doses will be selected from Part 1 and SCLC participants will be assigned to one of these doses in a randomized fashion to determine the recommended Phase 2 dose. In Part 3a, participants with SCLC or NECs will receive ABBV-706 in combination with budigalimab intravenously every 3 weeks. In Part 3b participants with SCLC or NECs will receive ABBV-706 in combination with either carboplatin or cisplatin intravenously. In Part 4a, participants with CNS tumors will receive ABBV-706 intravenously at a dose determined from Part 1. In Part 4b, participants with NECs will receive ABBV-706 intravenously at a dose selected from Part 1. The estimated duration of the study is up to 3 years.

There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at a hospital or clinic and may require frequent medical assessments, blood tests, and scans.

Study Overview

• Status: Recruiting
• Conditions: Advanced Solid Tumors
• Intervention / Treatment: Drug: ABBV-706; Drug: Budigalimab; Drug: Cisplatin; Drug: Carboplatin

• Study Type: Interventional
• Enrollment (Estimated): 350
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: ABBVIE CALL CENTER; Phone Number: 844-663-3742; Email: abbvieclinicaltrials@abbvie.com

Study Locations

• Australia
  • Victoria
    • Heidelberg, Victoria, Australia, 3084
      • Recruiting
      • Austin Health and Ludwig Institute for Cancer Research /ID# 255174
    • Melbourne, Victoria, Australia, 3000
      • Recruiting
      • Peter MacCallum Cancer Ctr /ID# 259197
• Israel
  • Jerusalem, Israel, 91120
    • Recruiting
    • Hadassah Medical Center-Hebrew University /ID# 255147
  • H_efa
    • Haifa, H_efa, Israel, 3109601
      • Recruiting
      • Rambam Health Care Campus /ID# 255059
  • Tel-Aviv
    • Ramat Gan, Tel-Aviv, Israel, 5265601
      • Recruiting
      • The Chaim Sheba Medical Center /ID# 254915
• Japan
  • Chiba
    • Kashiwa-shi, Chiba, Japan, 277-8577
      • Recruiting
      • National Cancer Center Hospital East /ID# 259417
  • Ehime
    • Matsuyama-shi, Ehime, Japan, 791-0280
      • Recruiting
      • National Hospital Organization Shikoku Cancer Center /ID# 261279
  • Hokkaido
    • Sapporo-shi, Hokkaido, Japan, 003-0804
      • Recruiting
      • Hokkaido Cancer Center /ID# 261278
  • Kyoto
    • Kyoto-shi, Kyoto, Japan, 606-8507
      • Recruiting
      • Kyoto University Hospital /ID# 259419
  • Shizuoka
    • Sunto-gun, Shizuoka, Japan, 411-8777
      • Recruiting
      • Shizuoka Cancer Center /ID# 261277
  • Tokyo
    • Koto, Tokyo, Japan, 135-8550
      • Recruiting
      • The Cancer Institute Hospital Of JFCR /ID# 260132
  • Wakayama
    • Wakayama-shi, Wakayama, Japan, 641-8510
      • Recruiting
      • Wakayama Medical University Hospital /ID# 260131
• Korea, Republic of
  • Seoul, Korea, Republic of, 03080
    • Recruiting
    • Seoul National University Hospital /ID# 248940
  • Seoul, Korea, Republic of, 06351
    • Recruiting
    • Samsung Medical Center /ID# 248936
  • Gyeonggido
    • Goyang-si, Gyeonggido, Korea, Republic of, 10408
      • Recruiting
      • National Cancer Center /ID# 248938
    • Seongnam, Gyeonggido, Korea, Republic of, 13496
      • Recruiting
      • CHA Bundang Medical Center /ID# 248939
  • Jeonranamdo
    • Hwasun-gun, Jeonranamdo, Korea, Republic of, 58128
      • Recruiting
      • Chonnam National University Hwasun Hospital /ID# 248943
  • Seoul Teugbyeolsi
    • Seoul, Seoul Teugbyeolsi, Korea, Republic of, 03722
      • Recruiting
      • Yonsei University Health System Severance Hospital /ID# 248937
• Spain
  • Madrid, Spain, 28050
    • Recruiting
    • Hospital Universitario HM Sanchinarro /ID# 258657
  • Madrid, Spain, 28034
    • Recruiting
    • Hospital Universitario Ramon y Cajal /ID# 257291
• United States
  • Arizona
    • Gilbert, Arizona, United States, 85234
      • Recruiting
      • Banner MD Anderson Cancer Ctr /ID# 260129
  • California
    • Duarte, California, United States, 91010
      • Recruiting
      • City of Hope /ID# 259884
  • Connecticut
    • New Haven, Connecticut, United States, 06519
      • Recruiting
      • Yale School of Medicine /ID# 246647
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Recruiting
      • Georgetown University Hospital /ID# 255352
  • Indiana
    • Fort Wayne, Indiana, United States, 46804
      • Recruiting
      • Fort Wayne Medical Oncology and Hematology, Inc /ID# 260130
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • Recruiting
      • University of Iowa Hospitals and Clinics /ID# 246638
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Recruiting
      • Henry Ford Hospital /ID# 246648
    • Detroit, Michigan, United States, 48201
      • Recruiting
      • Barbara Ann Karmanos Cancer In /ID# 261799
    • Grand Rapids, Michigan, United States, 49546-7062
      • Recruiting
      • START Midwest /ID# 251257
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Recruiting
      • Washington University-School of Medicine /ID# 246286
  • New York
    • New York, New York, United States, 10065-6007
      • Recruiting
      • Memorial Sloan Kettering Cancer Center-Koch Center /ID# 246303
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Recruiting
      • Duke Cancer Center /ID# 246285
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • Recruiting
      • UH Cleveland Medical Center /ID# 246641
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73117
      • Recruiting
      • Univ Oklahoma HSC /ID# 250884
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Recruiting
      • Tennessee Oncology, PLLC /ID# 246283
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • University of Texas MD Anderson Cancer Center /ID# 246287
    • San Antonio, Texas, United States, 78229
      • Recruiting
      • South Texas Accelerated Research Therapeutics /ID# 248946
  • Utah
    • Salt Lake City, Utah, United States, 84112-5500
      • Recruiting
      • University of Utah /ID# 246640
  • Washington
    • Tacoma, Washington, United States, 98405
      • Recruiting
      • Northwest Medical Specialties - Tacoma /ID# 262801

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• The laboratory values criteria must be met within 7 days prior to the first dose of study drug as per the protocol.
• QT interval corrected for heart rate (QTc) <= 450 msec (males) or <= 470 msec (females) using Fridericia's correction, and an ejection fraction of >= 50% as measured by echocardiogram or multigated acquisition (MUGA) scan at Screening.
• Part 1 only: Advanced recurrent or refractory solid tumors with potential SEZ6 expression including small cell lung cancer (SCLC), high-grade central nervous system (CNS) tumors (glioblastoma [GBM], IDH-wildtype Grade 4; oligodendroglioma, IDH-mutant, and 1p/19q-codeleted Grade 3; astrocytoma, IDH-mutant Grade 3 or Grade 4), neuroendocrine prostate cancer (NEPC), high-grade poorly differentiated gastroenteropancreatic neuroendocrine carcinoma (GEP-NEC)s, large cell neuroendocrine carcinoma (LCNEC)s, SCLC transformed from epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer (NSCLC), atypical lung carcinoids, and other high-grade poorly differentiated NECs, who have progressed on or after standard of care (SoC) therapy and with no curative therapy available. For SCLC, participants must have histologically or cytologically confirmed SCLC that is relapsed or refractory following at least 1 prior platinum-containing chemotherapy.
• Part 2 only: Histologically or cytologically confirmed SCLC that is relapsed or refractory (R/R) following at least 1 prior platinum-containing chemotherapy and with no curative therapy available. For the purposes of this study, a line of therapy is defined as >= 1 complete cycle of either a single agent or combination of drugs, including any planned sequential therapy of various regimens.
• Part 3a only: Participants with R/R SCLC following at least 1 prior platinum-containing chemotherapy or R/R poorly differentiated NECs, e.g., NEPC, GEP-NECs, LCNECs, SCLC transformed from EGFR mutant Non-small cell lung cancer (NSCLC), atypical lung carcinoids, other high-grade poorly differentiated NECs.
• Part 3b only: Participants with R/R SCLC who have only progressed following a frontline regimen containing a platinum-based chemotherapy or R/R NECs, e.g., NEPC, GEP-NECs, LCNECs, SCLC transformed from EGFR mutant NSCLC, atypical lung carcinoids, other NECs.
• Part 4a only: Participants with R/R high-grade CNS tumors (GBM, IDH-wildtype Grade 4; oligodendroglioma, IDH-mutant, and 1p/19q-codeleted Grade 3; astrocytoma, IDH-mutant Grade 3 or Grade 4) who have progressed on SoC therapy and with no curative therapy options available.
• Part 4b only: Participants with R/R neuroendocrine tumors, including NEPC, GEP-NECs, LCNECs, SCLC transformed from EGFR mutant NSCLC, atypical lung carcinoids, and other high-grade poorly differentiated NECs, who have progressed on SoC therapy and with no curative therapy options available.
• Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 for participants with extracranial solid tumors or Response Assessment for Neuro-Oncology (RANO)for participants with primary high-grade CNS tumors (GBM, IDH-wildtype Grade 4; oligodendroglioma, IDH-mutant, and 1p/19q-codeleted Grade 3; astrocytoma, IDH-mutant Grade 3 or Grade 4).
• Primary CNS tumors within 12 weeks from radiation therapy should have unequivocal progression as documented by either tumor recurrence predominantly outside of radiation field on magnetic resonance imaging (MRI) or confirmed on tumor biopsy.
• Participants with brain metastases from an extracranial solid tumor are eligible if the brain metastases as outlined in the protocol.
• Fresh or archival tumor tissue available for submission, for retrospective SEZ6 expression analysis as outlined in the protocol.

Exclusion Criteria:

• History of interstitial lung disease (ILD) or pneumonitis that required treatment with systemic steroids, nor any evidence of active ILD or pneumonitis.
• History of idiopathic pulmonary fibrosis or organizing pneumonia.
• Prior treatment with an antibody drug conjugate that consists of a Top1 inhibitor payload.
• Part 2 only: Prior treatment with a SEZ6-targeted antibody drug conjugate.

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

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1: ABBV-706 Monotherapy Dose Escalation; Participants will receive escalating doses of ABBV-706 until doses for optimization are determined, as part of an approximately 1 year treatment period.	Drug: ABBV-706; Intravenous (IV) Infusion
Experimental: Part 2: ABBV-706 Monotherapy Dose Optimization and Expansion; Participants with small cell lung cancer will receive varying doses of ABBV-706 in a randomized manner until the recommended phase 2 dose (RP2D) is achieved, as part of an approximately 1 year treatment period..	Drug: ABBV-706; Intravenous (IV) Infusion
Experimental: Part 3a: ABBV-706 + Budigalimab; Participants will receive ABBV-706 in combination with budigalimab, as part of an approximately 1 year treatment period.	Drug: ABBV-706; Intravenous (IV) Infusion; Drug: Budigalimab; IV Infusion; Other Names: ABBV-181
Experimental: Part 3b: ABBV-706 + Platinum Chemotherapy; Participants will receive ABBV-706 in combination with carboplatin or cisplatin, as part of an approximately 1 year treatment period.	Drug: ABBV-706; Intravenous (IV) Infusion; Drug: Cisplatin; Intravenous infusion; Drug: Carboplatin; Intravenous infusion
Experimental: Part 4a: ABBV-706 Monotherapy Dose Expansion CNS Tumors; Participants with relapsed/refractory (R/R) central nervous system (CNS) tumors will receive ABBV-706 as a monotherapy at or below the maximum tolerated dose (MTD) maximum administered dose (MAD), as part of an approximately 1 year treatment period.	Drug: ABBV-706; Intravenous (IV) Infusion
Experimental: Part 4b: ABBV-706 Monotherapy Dose Expansion NECs; Participants with R/R neuroendocrine carcinomas (NECs) will receive IV Infused ABBV-706 as a monotherapy at or below the MTD/MAD, as part of an approximately 1 year treatment period.	Drug: ABBV-706; Intravenous (IV) Infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Adverse Events (AE)	An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment.	Up to Approximately 2 Years
Maximum Observed Serum/Plasma Concentration (Cmax) of ABBV-706	Maximum observed serum/plasma concentration of ABBV-706.	Up to Approximately 2 Years
Time to Cmax (Tmax) of ABBV-706	Time to Cmax of ABBV-706.	Up to Approximately 2 Years
Terminal Phase Elimination Half-Life (t1/2) of ABBV-706	Terminal phase elimination half-life (t1/2) of ABBV-706.	Up to Approximately 2 Years
Area Under the Serum/Plasma Concentration-Time Curve (AUC) of ABBV-706	Area under the serum/plasma concentration-time curve of ABBV-706.	Up to Approximately 2 Years
Antidrug Antibodies (ADAs)	Incidence and concentration of anti-drug antibodies.	Up to Approximately 2 Years
Neutralizing Antibodies (nAbs)	Incidence and concentration of neutralizing antibodies.	Up to Approximately 2 Years
Percentage of Participants with Objective Response, for Participants with Extracranial Solid Tumors	Objective response is defined as participants achieving a confirmed best overall response of complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1 for for extracranial solid tumors per investigator assessment.	Up to Approximately 2 Years
Recommended Phase 2 Dose (RP2D) of ABBV-706	The RP2D will be determined using all available information, including, but not limited to, AEs, dose-limiting toxicities, pharmacokinetic parameters, clinical laboratory tests, and efficacy measures.	Up to Approximately 2 Years
Percentage of Participants with Objective Response for Participants with Central Nervous System (CNS) Tumors	Objective response is as participants achieving a confirmed best overall response of CR and PR according to Response Assessment for Neuro-Oncology (RANO), version 1.1 for CNS tumors per investigator assessment.	Up to Approximately 2 Years
Duration of response (DOR) for Participants with Confirmed CR/PR	For participants achieving a confirmed CR/PR, DOR is defined as the time from the initial response of CR/PR to disease progression or death of any cause, whichever occurs earlier.	Up to Approximately 2 Years
Percentage of Participants with Clinical Benefit	Clinical benefit is defined as a participant achieving CR/PR, or Stable Disease (SD).	Up to Approximately 2 Years
Progression-Free Survival (PFS)	PFS is defined as time from first study treatment to a documented disease progression, as determined by the investigator, or death due to any cause, whichever occurs earlier.	Up to Approximately 2 Years
Overall survival (OS)	OS is defined as time from first study treatment to death due to any cause.	Up to Approximately 2 Years

Collaborators and Investigators

• Sponsor: AbbVie
• Investigators: Study Director: ABBVIE INC., AbbVie

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): December 5, 2022
• Primary Completion (Estimated): October 15, 2025
• Study Completion (Estimated): October 15, 2025

Study Registration Dates

• First Submitted: October 28, 2022
• First Submitted That Met QC Criteria: October 28, 2022
• First Posted (Actual): October 31, 2022

Study Record Updates

• Last Update Posted (Actual): April 24, 2024
• Last Update Submitted That Met QC Criteria: April 22, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Cancer; Cisplatin; Carboplatin; Advanced Solid Tumors; Small Cell Lung Cancer; ABBV-181; Budigalimab; Central Nervous System Tumors; ABBV-706; Platinum Chemotherapy Combination; Neuroendocrine Carcinomas
• Additional Relevant MeSH Terms: Neoplasms; Antineoplastic Agents; Carboplatin
• Other Study ID Numbers: M23-385

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: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes