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 (AndroMETa-GEA)

AbbVie

Status and phase: Enrolling; Phase 2

Conditions: Locally Advanced Unresectable or Metastatic Gastric Adenocarcinoma; Esophageal Adenocarcinoma; Gastroesophageal Junction Adenocarcinoma

Treatments: Drug: Budigalimab; Drug: ABBV-400; Drug: Oxaliplatin; Drug: Leucovorin; Drug: Fluorouracil

Study type: Interventional

Funder types: Industry

Identifiers

NCT06628310

2024-513008-32 (Other Identifier)

M24-977

Details and patient eligibility

About

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 ABBV-400 is given in combination with Fluorouracil, Leucovorin, and a programmed cell death receptor 1 (PD1) inhibitor (Budigalimab) (AFLB) to adult participants to treat locally advanced unresectable or metastatic gastric, gastroesophageal junction, or esophageal adenocarcinoma (mGEA).

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 fluorouracil, leucovorin, and oxaliplatin (FOLFOX). 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 ABBV-400 within the AFLB regimen until the dose reached is tolerable and expected to be efficacious. In the dose optimization stage participants will be receive FOLFOX or receive AFLB, but with one of two optimized doses of ABBV-400The 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.

Enrollment: 180 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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 local or 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: Quadruple Blind

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180 participants in 4 patient groups

Stage 1: Dose Escalation ABBV-400

Experimental group

Description:

Participants will receive escalating doses of ABBV-400 in combination with a fixed dose of fluorouracil, leucovorin and budigalimab as part of the approximately 6 year study duration.

Treatment:

Drug: Fluorouracil

Drug: Leucovorin

Drug: Budigalimab

Drug: ABBV-400

Stage 2 Arm 1: Dose Optimization ABBV-400 Dose A

Experimental group

Description:

Participants will receive ABBV-400 dose A in combination with a fixed dose of fluorouracil, leucovorin and budigalimab as part of the approximately 6 year study duration.

Treatment:

Drug: Fluorouracil

Drug: Leucovorin

Drug: Budigalimab

Drug: ABBV-400

Stage 2 Arm 2: Dose Optimization ABBV-400 Dose B

Experimental group

Description:

Participants will receive ABBV-400 dose B in combination with a fixed dose of fluorouracil, leucovorin and budigalimab as part of the approximately 6 year study duration.

Treatment:

Drug: Fluorouracil

Drug: Leucovorin

Drug: Budigalimab

Drug: ABBV-400

Stage 2 Arm 3: Dose Optimization Standard of Care (SOC)

Experimental group

Description:

Participants will receive a fixed dose of leucovorin (folinic acid), fluorouracil, oxaliplatin (FOLFOX) and budigalimab as part of the approximately 6 year study duration.

Treatment:

Drug: Fluorouracil

Drug: Leucovorin

Drug: Oxaliplatin

Drug: Budigalimab