A Phase 2 Randomized Study to Evaluate the Safety, Efficacy, and Optimal Dose of Telisotuzumab Adizutecan in Combination with Fluorouracil, Leucovorin, and Budigalimab as First-Line Treatment in Subjects with Locally Advanced Unresectable or Metastatic Gastric, Gastroesophageal Junction, or Esophageal Adenocarcinoma (AndroMETa-GEA-977)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

AbbVie Deutschland GmbH & Co. KG

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Digestive System Diseases [C06]

Trial duration

17 Dec 2025 → ongoing

Decision date (initial)

2025-03-24

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

AbbVie Inc.

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Dose response, Efficacy

The study will address the hypothesis that Telisotuzumab Adizutecan in combination with 5-FU, LV, and budigalimab can be safely administered and improve clinical outcomes compared to FOLFOX and budigalimab in subjects with previously untreated advanced or metastatic gastric/gastroesophageal junction adenocarcinoma (GEA).

The primary objectives are:
• To evaluate the safety and tolerability of Telisotuzumab Adizutecan in combination with 5-FU, LV, and budigalimab.
• To select the RP3D of Telisotuzumab Adizutecan in combination with 5-FU, LV, and budigalimab.
• To evaluate the efficacy as measured by PFS and OR of Telisotuzumab Adizutecan in combination with 5-FU, LV, and budigalimab.

Secondary objectives 3

1. To assess Telisotuzumab Adizutecan in combination with 5-FU, LV, and budigalimab for DLT in the dose escalation.
2. To evaluate the efficacy of Telisotuzumab Adizutecan in combination with 5-FU, LV, and budigalimab as measured DoR, DC, and OS.
3. To evaluate the PK of Telisotuzumab Adizutecan in combination with 5-FU, LV, and budigalimab.

Conditions and MedDRA coding

Adenocarcinoma of the gastroesophageal junction

Regulatory references

Scientific advice from competent authorities

European Medicines Agency, Food And Drug Administration

Plan to share IPD

Yes

IPD plan description

AbbVie is committed to responsible clinical trial data sharing. This includes access to anonymized, individual and trial level data (analysis data sets), as well as other information. To learn more about the process, or to submit a request, visit https://www.abbvieclinicaltrials.com/hcp/data-sharing/ For details on when studies are available for sharing, visit https://vivli.org/ourmember/abbvie/

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 17

1. Subjects or their legally authorized representative must voluntarily sign and date an informed consent, approved by an independent ethics committee (IEC)/institutional review board (IRB), prior to the initiation of any screening or study-specific procedures.
2. Are willing and able to comply with procedures required in this protocol.
3. Adult individuals, at least 18 years old (or acceptable age according to local regulations, whichever is older).
4. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1.
5. Laboratory values meeting the following criteria within the screening period prior to the first dose of study drug: Serum ALT and AST ≤ 3.0 × ULN within 7 days before Cycle 1 Day 1 dosing; Subjects with liver metastases may have AST and ALT ≤ 5.0 × ULN; eGFR ≥ 30 mL/min/1.73 m2 as calculated by CKD-EPI ; Total bilirubin ≤ 1.5 × ULN within 7 days before Cycle 1 Day 1 dosing (subjects with documented Gilbert's syndrome may have a total bilirubin ≤ 3 × ULN); ANC ≥ 1,500/mm3 (with no G-CSF within 10 days prior to Cycle 1 Day 1 dosing); Platelet count ≥ 100,000/μL (with no platelet transfusion within 14 days prior to Cycle 1 Day 1 dosing); Hemoglobin ≥ 8 g/dL (with no RBC transfusion within 14 days prior to Cycle 1 Day 1 dosing); Albumin ≥ 3 g/dL.
6. QTc < 470 msec (using Fridericia's correction), no Grade 3 arrythmia, and no other clinically significant cardiac abnormalities
7. Echocardiogram with ejection fraction ≥ 50% and no other clinically significant cardiac abnormalities that in the opinion of the investigator, would increase the subject's susceptibility to cardiac toxicity
8. No history of cardiac disease including congestive heart failure Class II or higher New York Heart Association; active coronary artery disease, myocardial infarction within 6 months prior to study entry; unevaluated new onset angina within 3 months or unstable angina (angina symptoms at rest) or cardiac arrhythmias requiring antiarrhythmic therapy (beta-blockers or digoxin are permitted).
9. Resolution of any acute clinically significant treatment-related toxicity from prior therapy to Grade ≤ 1 prior to study entry (except for alopecia of any grade).
10. Documented virology HBV and HCV testing, with enrollment allowed as follows: If a subject has a positive HBsAg, HBsAb, and/or HBcAb test at screening, an HBV DNA test should be performed. If HBV DNA is detected (≥ 10 IU/mL or above the limit of detection), subject must agree to initiate anti-HBV treatment (per local SOC) a minimum of 14 days prior to first dose of study drug and be willing to continue treatment for the study duration and for at least 6 months after the last dose of study drug. Subjects with HBV infection will be allowed to enroll if they meet the following criteria: HBV DNA < 500 IU/mL obtained within 35 days prior to initiation of study treatment, AND anti-HBV treatment (per local SOC) for a minimum of 14 days prior to first dose and willingness to continue treatment for the study duration and for at least 6 months after the last dose of study drug. Ongoing antiviral therapy that includes strong CYP3A inhibitors should be used with caution and assessed for any potential for risk of adverse drug-drug interactions, at the discretion of the treating investigator. Subjects with resolved HBV infection (HBsAg-negative, HBcAb-positive) are eligible if they are willing to comply with HBV DNA monitoring while on study drug and agree to initiate antiviral therapy if HBV DNA becomes detectable (≥ 10 IU/mL or above the limit of detection). Subjects with a negative HBcAb and positive HBsAb at screening must agree to comply with HBV DNA monitoring if they have no prior history of receiving a complete hepatitis B vaccination series or where locally mandated.
11. Subjects infected with HIV may be enrolled if CD4 count is ≥ 100 cells/μL. If CD4 count is < 200 cells/μL, a CD4 to CD8 ratio > 0.4 is required. Subject must have been receiving effective ART for at least 4 weeks with an HIV viral load of less than 200 copies/mL, and subject must have no symptomatic AEs higher than Grade 1 attributed to ART. Ongoing ART that includes strong CYP3A inhibitors should be used with caution and assessed for any potential for risk of adverse drug-drug interactions, at the discretion of the treating investigator.
12. All subjects must consent to provide archived FFPE tumor tissue. If archived tissue is not available, a fresh tumor biopsy is required. Enrollment without tumor tissue must be agreed upon in advance by the AbbVie medical monitor.
13. Subject has inoperable, advanced or metastatic histologically- or cytologically- confirmed gastric, gastro-esophageal junction, or esophageal adenocarcinoma.
14. HER2 negative disease, defined as IHC 0 or 1+ or FISH negative. FISH can be replaced with locally available ISH methods acceptable as per institutional guidelines.
15. For Stage 2 only: known PD-L1 status at screening, or availability of tumor tissue for local or central PD-L1 testing prior to randomization. PD-L1 test results must be available prior to Stage 2 randomization.
16. No prior systemic therapy in the locally advanced, unresectable, or metastatic setting. Subjects may have received prior neoadjuvant and/or adjuvant therapy as long as it was completed at least 6 months prior to randomization/enrollment.
17. Measurable disease per RECIST1.1 at baseline. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.

Exclusion criteria 18

1. Has squamous cell or undifferentiated gastric cancer
2. Prior cMET targeting therapy
3. Prior PD-1 or PD-L1 checkpoint inhibitor
4. History of ILD or pneumonitis that required treatment with systemic steroids, or any evidence of active ILD or pneumonitis on screening chest CT scan, including a history of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis.
5. History of clinically significant, intercurrent lung-specific illnesses including, but not limited to: Underlying pulmonary disorder (i.e., pulmonary emboli within 3 months of the study enrollment, severe asthma, severe chronic obstructive pulmonary disease, restrictive lung disease, pleural effusion, dependence on supplemental oxygen etc.); Any autoimmune, connective tissue or inflammatory disorders with documented or suspicious pulmonary involvement at screening (i.e., rheumatoid arthritis, Sjogren's, sarcoidosis etc.), and prior pneumonectomy.
6. Has had major surgery or significant traumatic injury within 28 days prior to randomization/enrollment, or anticipation of the need for major surgery during the course of study intervention.
7. Current or prior use of immunosuppressive therapy within 14 days prior to the first dose of study intervention.
8. Has an active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease-modifying agents, corticosteroids or immunosuppressive drugs), with exceptions of vitiligo, type I diabetes mellitus, hypothyroidism, and psoriasis. Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed.
9. Subject has another malignancy for which treatment is required per investigator's clinical judgment or subjects with prior history of another malignancy except for malignancy treated with curative intent with no known active disease within 6 months before the first dose of study intervention.
10. Has known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable (i.e., without evidence of progression) for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study intervention.
11. Has an active or chronic infection that requires systemic antibacterial, antifungal or antiviral therapy and that remains unresolved within 14 days prior to randomization or first dose of study drugs.
12. Prior bone marrow transplant, solid organ transplant, or previous clinical diagnosis of tuberculosis.
13. Has a known severe hypersensitivity (≥ Grade 3) to any of the study agents and/or to any of their excipients and/or other products in the same class.
14. Grade ≥ 3 major immunologic reaction to any IgG-containing agent. Subjects that have already received subsequent therapy with another IgG-containing agent following a Grade ≤ 2 reaction may be eligible after discussion with the Therapeutic Area Medical Director.
15. Has a history or current evidence of any condition (e.g., known dihydropyrimidine dehydrogenase deficiency), therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating investigator. Screening for dihydropyrimidine dehydrogenase deficiency should be conducted per local requirements.
16. History of clinically significant medical or psychiatric conditions or any other reason that the investigator determines would interfere with the subject's participation in this study or would make the subject an unsuitable candidate to receive study drug.
17. History of clinically significant (per investigator's judgment) drug or alcohol abuse within the last 6 months. Legal cannabis and/or THC use is allowed.
18. Is pregnant or breastfeeding or expecting to conceive within the projected duration of the study.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. 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. Subjects with no PFS event will be censored at the last evaluable radiographic assessment. Subjects with no event and no evaluable post-baseline assessment will be censored at the first dose date
2. Overall survival (OR) as assessed by investigator: Confirmed complete response (CR) or confirmed partial response (PR) as assessed by investigator per RECIST version 1.1. Response will need to be confirmed by a repeat assessment no less than 28 days from the first documented response.

Secondary endpoints 3

1. Duration of Response (DoR) as assessed by investigator: The time from the first documented CR or PR to the first occurrence of radiographic progression per RECIST version 1.1 as determined by investigator or death from any cause, whichever occurs first. DoR is defined for subjects with confirmed CR/PR.
2. Disease control (DC) as assessed by investigator: best overall response of confirmed CR or confirmed PR, or stable disease (SD) (with a minimum duration of 16 weeks) based on RECIST, version 1.1 as determined by the investigator
3. Overall survival (OR) is defined as the time from first dose of study drug to the event of death from any cause. Subjects with no documented death will be censored at the last known alive date.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 4

Comparator 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

AbbVie Deutschland GmbH & Co. KG

Sponsor organisation

AbbVie Deutschland GmbH & Co. KG

Address

Knollstrasse

City

Ludwigshafen Am Rhein

Postcode

67061

Country

Germany

Scientific contact point

Organisation

AbbVie Deutschland GmbH & Co. KG

Contact name

Global Clinical Trials Helpdesk

Public contact point

Organisation

AbbVie Deutschland GmbH & Co. KG

Contact name

Global Clinical Trials Helpdesk

Third parties 8

Locations

3 EU/EEA countries · 12 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 34 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications