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

ConditionsLocally Advanced Unresectable or Metastatic Gastric Adenocarcinoma Gastroesophageal Junction Adenocarcinoma Esophageal Adenocarcinoma

Trial statusRecruiting

Trial phasePhase 2

Trial typeInterventional

Biological sexAll

Age18+

SponsorAbbVie

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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.

Disqualifiers

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

Design model

Sequential

Treatments tested in this trial

Telisotuzumab Adizutecan
Drug
Intravenous (IV) Infusion
Budigalimab
Drug
IV Infusion
Fluorouracil
Drug
IV Infusion; IV Injection
Leucovorin
Drug
IV Infusion; IV Injection
Oxaliplatin
Drug
IV Infusion

Treatment groups

180 Participants

are divided into 4 treatment groups

Group A: Stage 1: Dose Escalation ABBV-400Experimental treatment 4 interventions

Group B: Stage 2 Arm 1: Dose Optimization ABBV-400 Dose AExperimental treatment 4 interventions

Group C: Stage 2 Arm 2: Dose Optimization ABBV-400 Dose BExperimental treatment 4 interventions

Group D: Stage 2 Arm 3: Dose Optimization Standard of Care (SOC)Experimental treatment 4 interventions

Trial outcomes

Primary outcomes

Progression-Free Survival (PFS) as Assessed by Investigator

PFS is defined as the time from the first dose of study drug to the first occurrence of radiographic progression based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 as determined by investigator or death from any cause, whichever occurs earlier.

Time frame