A Study to Evaluate the Adverse Events, Efficacy, and Optimal Dose of Intravenous (IV) ABBV-400 in Combination With IV Fluorouracil, Leucovorin, and Budigalimab in Adult Participants With Locally Advanced Unresectable or Metastatic Gastric, Gastroesophageal Junction, or Esophageal Adenocarcinoma

Purpose

Cancer is a condition where cells in a specific part of body grow and reproduce uncontrollably. The purpose of this study is to assess adverse events and change in disease activity when telisotuzumab adizutecan (ABBV-400) is given in combination with Fluorouracil, Leucovorin, and a programmed cell death receptor 1 (PD1) inhibitor Budigalimab. The combination (AFLB) will be given to adult participants to treat locally advanced unresectable or metastatic gastric, gastroesophageal junction, or esophageal adenocarcinoma (mGEA). Telisotuzumab Adizutecan (ABBV-400) and Budigalimab are investigational drugs being developed for the treatment of mGEA. Fluorouracil and Leucovorin are drugs approved for the treatment of mGEA. This study will be divided into two stages, with the first stage treating participants with increasing doses of ABBV-400 within the AFLB regimen until the dose reached is tolerable and expected to be efficacious. Participants will then be randomized into groups called treatment arms where one group will receive Budigalimab and FOLFOX (Fluorouracil, Leucovorin, and Oxaliplatin) . A further two treatment groups will receive AFLB, but with two optimized doses of ABBV-400 to allow for the best dose to be studied in the future. Approximately 180 adult participants with mGEA will be enrolled in the study in 51 sites worldwide. In the dose escalation stage, participants will be treated with increasing intravenous (IV) doses of telisotuzumab adizutecan (ABBV-400) within the AFLB regimen until the dose reached is tolerable and expected to be efficacious. In the dose optimization stage, participants will receive FOLFOX or receive AFLB, but with one of two optimized doses of ABBV-400. The study will run for a duration of approximately 6 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 an approved institution (hospital or clinic). The effect of the treatment will be frequently checked by medical assessments, blood tests, questionnaires and side effects.

Conditions

  • Locally Advanced Unresectable or Metastatic Gastric Adenocarcinoma
  • Gastroesophageal Junction Adenocarcinoma
  • Esophageal Adenocarcinoma

Eligibility

Eligible Ages
Over 18 Years
Eligible Sex
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  • Have inoperable, advanced or metastatic histologically- or cytologically confirmed gastric, gastroesophageal junction, or esophageal adenocarcinoma. - Have measurable disease determined using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. - Have an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1. - Human epidermal growth factor receptor 2 (HER2) negative disease, defined as immunohistochemistry (IHC) (0, or 1+) or fluorescence in situ hybridization (FISH) negative. - Known programmed death ligand 1 (PD-L1) status at screening, or availability of tumor tissue for central PD-L1 testing prior to enrollment.

Exclusion Criteria

  • Have prior systemic therapy in the locally advanced, unresectable, or metastatic setting. - History of clinically significant, intercurrent lung-specific illnesses including, but not limited to those listed in the protocol.

Study Design

Phase
Phase 2
Study Type
Interventional
Allocation
Randomized
Intervention Model
Sequential Assignment
Primary Purpose
Treatment
Masking
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Stage 1: Dose Escalation ABBV-400 		Participants will receive escalating doses of telisotuzumab adizutecan (ABBV-400) in combination with a fixed dose of fluorouracil, leucovorin and budigalimab as part of the approximately 6 year study duration.
  • Drug: Telisotuzumab Adizutecan
    Intravenous (IV) Infusion
    Other names:
    • ABBV-400
  • Drug: Budigalimab
    IV Infusion
    Other names:
    • ABBV-181
  • Drug: Fluorouracil
    IV Infusion; IV Injection
  • Drug: Leucovorin
    IV Infusion; IV Injection
    Other names:
    • Folinic Acid
Experimental
Stage 2 Arm 1: Dose Optimization ABBV-400 Dose A 		Participants will receive telisotuzumab adizutecan (ABBV-400) dose A in combination with a fixed dose of fluorouracil, leucovorin and budigalimab as part of the approximately 6 year study duration.
  • Drug: Telisotuzumab Adizutecan
    Intravenous (IV) Infusion
    Other names:
    • ABBV-400
  • Drug: Budigalimab
    IV Infusion
    Other names:
    • ABBV-181
  • Drug: Fluorouracil
    IV Infusion; IV Injection
  • Drug: Leucovorin
    IV Infusion; IV Injection
    Other names:
    • Folinic Acid
Experimental
Stage 2 Arm 2: Dose Optimization ABBV-400 Dose B 		Participants will receive telisotuzumab adizutecan (ABBV-400) dose B in combination with a fixed dose of fluorouracil, leucovorin and budigalimab as part of the approximately 6 year study duration.
  • Drug: Telisotuzumab Adizutecan
    Intravenous (IV) Infusion
    Other names:
    • ABBV-400
  • Drug: Budigalimab
    IV Infusion
    Other names:
    • ABBV-181
  • Drug: Fluorouracil
    IV Infusion; IV Injection
  • Drug: Leucovorin
    IV Infusion; IV Injection
    Other names:
    • Folinic Acid
Experimental
Stage 2 Arm 3: Dose Optimization Standard of Care (SOC) 		Participants will receive a fixed dose of leucovorin (folinic acid), fluorouracil, oxaliplatin (FOLFOX) and budigalimab as part of the approximately 6 year study duration.
  • Drug: Budigalimab
    IV Infusion
    Other names:
    • ABBV-181
  • Drug: Fluorouracil
    IV Infusion; IV Injection
  • Drug: Leucovorin
    IV Infusion; IV Injection
    Other names:
    • Folinic Acid
  • Drug: Oxaliplatin
    IV Infusion

Recruiting Locations

City of Hope National Medical Center /ID# 268690
Duarte 5344147, California 5332921 91010

City of Hope - Orange County Lennar Foundation Cancer Center /ID# 272630
Irvine 5359777, California 5332921 92618

UCLA - Santa Monica /ID# 270024
Santa Monica 5393212, California 5332921 90404

Hattiesburg Clinic /ID# 268572
Hattiesburg 4429295, Mississippi 4436296 39401

Duke University Medical Center /ID# 268186
Durham 4464368, North Carolina 4482348 27710

Millennium Research & Clinical Development /ID# 268540
Houston 4699066, Texas 4736286 77090

Pan American Center for Oncology Trials /ID# 268833
Rio Piedras 4829037, Puerto Rico 00935

More Details

Status
Recruiting
Sponsor
AbbVie

Study Contact

ABBVIE CALL CENTER
844-663-3742
abbvieclinicaltrials@abbvie.com