Bemarituzumab plus Chemotherapy and Nivolumab versus Chemotherapy and Nivolumab Alone (FORTITUDE-102)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Amgen Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

13 Sep 2022 → 29 Oct 2025

Decision date (initial)

2024-02-26

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Amgen Inc.

External identifiers

EU CT number

2023-505458-16-00

EudraCT number

2021-003477-61

WHO UTN

U1111-1299-3375

ClinicalTrials.gov

NCT05111626

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

Phase 1b: To evaluate the safety and tolerability of bemarituzumab plus mFOLFOX6 and nivolumab
Phase 3: To compare efficacy of bemarituzumab plus chemotherapy and nivolumab to placebo plus chemotherapy and nivolumab as assessed by overall survival (OS) in subjects with FGFR2b ≥ 10% 2+/3+ tumor cell staining (FGFR2b ≥ 10% 2+/3+ TC)

Secondary objectives 10

1. Phase 1b: To evaluate preliminary anti-tumor activity of bemarituzumab plus mFOLFOX6 and nivolumab
2. Phase 1b: To characterize the pharmacokinetic (PK) profile of bemarituzumab when administered with mFOLFOX6 and nivolumab
3. Phase 1b: To characterize the immunogenicity of bemarituzumab
4. Phase 3: To compare efficacy between the treatment arms as assessed by progression-free survival in FGFR2b ≥ 10% 2+/3+ TC subjects
5. Phase 3: To compare efficacy between the treatment arms in all randomised subjects as assessed by: - OS - PFS
6. Phase 3: To evaluate the safety and tolerability of bemarituzumab plus chemotherapy and nivolumab compared to placebo plus chemotherapy and nivolumab
7. Phase 3: To compare efficacy between the treatment arms as assessed by: - Objective Response (OR) - Duration of response (DOR) - Disease control
8. Phase 3: To assess subject-reported and quality of life (QoL) outcomes in FGFR2b ≥ 10% 2+/3+ TC subjects
9. Phase 3: To characterize the pharmacokinetic (PK) profile of bemarituzumab when administered with chemotherapy and nivolumab
10. Phase 3: To characterize the immunogenicity of bemarituzumab

Conditions and MedDRA coding

Gastric and Gastroesophageal Junction Cancer With FGFR2b Overexpression

Study design 2 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. Adult with unresectable, locally advanced or metastatic (not amenable to curative therapy) histologically documented gastric or gastroesophageal junction adenocarcinoma
2. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
3. Measurable disease or non-measurable, but evaluable disease, according to Response Evaluation Criteria in Solid Tumours version 1.1 (RECIST v1.1)
4. Subject has no contraindications to nivolumab and either mFOLFOX6 or CAPOX chemotherapy as per local prescribing information. Subjects in Part 1 must have no contraindications to mFOLFOX6. Subjects in Part 2 with contraindications to mFOLFOX6 are permitted and may be administered the CAPOX regimen, if no contraindications for this regimen exist. Subjects in Part 2 with contraindications to CAPOX are permitted and may be administered the mFOLFOX6 regimen, if no contraindications for this regimen exist
5. Adequate organ function as follows: - Absolute neutrophil count . 1.5 x 10^9/L - Platelet count . 100 x 10^9/L - Hemoglobin . 9 g/dL without red blood cell (RBC) transfusion within 7 days prior to the first dose of study treatment - Aspartate aminotransaminase (AST) and Alanine aminotransaminase (ALT) <3 x upper limit of normal (ULN) (or < 5 x ULN if liver involvement). Total bilirubin <1.5 x ULN (or < 2 x ULN if liver involvement; or Gilbert's disease) - Calculated or measured creatinine clearance (CrCl) of . 50 mL/minute calculated using the formula of Cockcroft and Gault International Normalized Ratio (INR) or prothrombin time (PT) < 1.5 ~ ULN except for participants receiving anticoagulation, who must be on a stable dose of anticoagulant therapy for 6 weeks prior to enrollment.
6. Additional Inclusion criteria Phase 3:
7. No prior treatment for metastatic or unresectable disease except for a maximum of 1 dose of chemotherapy with or without nivolumab. Prior adjuvant, neo-adjuvant, and peri-operative therapy is allowed, provided it has been completed more than 6 months prior to the first dose of study treatment.
8. Confirmed FGFR2b ≥ 10% 2+/3+ TC by centrally performed immunohistochemistry (IHC) testing based on tumor sample either archival or a fresh biopsy.
9. For subjects receiving CAPOX only, the ability to take oral medication

Exclusion criteria 12

1. Prior treatment with any selective inhibitor of the fibroblast growth factor (FGF)-FGFR pathway
2. Known positive human epidermal growth factor receptor 2 (HER2) status
3. Untreated or symptomatic central nervous system disease metastases and leptomeningeal disease
4. Peripheral sensory neuropathy grade 2 or higher
5. Clinically significant cardiac disease
6. Other malignancy within the last 2 years (exceptions for definitively treated disease)
7. Chronic or systemic ophthalmologic disorders
8. Major surgery or other investigational study within 28 days prior to randomization
9. Palliative radiotherapy within 14 days prior to randomization
10. Evidence of, or recent (within 6 months) history of, corneal defects, corneal ulcerations, keratitis, or keratoconus, history of corneal transplant, or other known abnormalities of the cornea that may pose an increased risk of developing a corneal ulcer. Recent (within 6 months) corneal surgery or ophthalmic laser treatment
11. Active autoimmune disease that has required systemic treatment (except replacement therapy) within the past 2 years or any other diseases requiring immunosuppressive therapy while on study
12. For subjects receiving CAPOX only, GI tract disease causing the inability to take oral medication, malabsorption syndrome, or requirement for IV alimentation, or uncontrolled inflammatory GI disease (eg, Crohn's disease, ulcerative colitis)

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Phase 1b: Dose limiting toxicities (DLTs), treatment-emergent adverse events, treatment-related adverse events, and clinically significant changes in vital signs, visual acuity, physical examinations, and clinical laboratory tests
2. Phase 3: OS, defined as time from randomization until death from any cause. Subjects still alive will be censored at the date last known to be alive

Secondary endpoints 17

1. Phase 1b: - Objective response [defined as complete response (CR) + partial response (PR)] (as determined by investigator per Response Evaluation Criteria in Solid Tumors version 1.1 [RECIST v1.1]).
2. Phase 1b: - Duration of response (DOR) defined as the time from first response to disease progression (as determined by investigator per RECIST v1.1) or death from any cause, whichever comes first. Only subjects who have achieved objective response will b
3. Phase 1b: - Disease control rate (DCR) defined as CR + PR + stable disease (SD)
4. Phase 1b: -(PFS) defined as time from first dose of investigational product until the first documentation of radiologic disease progression (by investigator per RECIST v1.1) or death from any cause, whichever occurs first in the
5. Phase 1b: - Overall survival (OS), defined as time from first dose of investigational product until death from any cause. Subjects still alive will be censored at the date last known to be alive
6. Phase 1b: PK parameters for bemarituzumab, including, but not limited to, area under the concentration time curve (AUC), maximum observed concentration (Cmax), observed concentration at the end of a dose interval (Ctrough)
7. Phase 1b: Anti-bemarituzumab antibody formation
8. Phase 3: Progression-free survival, defined as time from randomization until the first documentation of radiologic disease progression or death from any cause, whichever occurs first in the absence of subsequent anticancer therapy. Progression-free surviv
9. Phase 3: - OS in all randomized subjects. - PFS in all randomized subjects
10. Phase 3: - Treatment-emergent adverse events (including all adverse events, grade ≥ 3, serious adverse events, fatal adverse events, and adverse events requiring permanent discontinuation of investigational product) - Clinically significant changes in vital signs, visual acuity, and clinical laboratory tests
11. Phase 3: -Objective response, defined as best overall response (BOR) of CR or PR (as determined by investigator per RECIST v1.1).
12. - Disease control defined as CR + PR + stable disease (SD).
13. Phase 3: - Subjective score and change from baseline in following assessments: - EORTC Quality of Life Questionnaire Version 3.0 (QLQ-C30) individual scores (raw and transformed) for the 5 functional scales, 9 symptom scales, global health status/quality
14. - Summary scores at each assessment and changes from baseline of visual analogue scale (VAS) scores as measured by EuroQol 5-dimensional (EQ-5D-5L) - Time to deterioration in stomach-cancer related symptoms scores - Time to deterioration in health-related
15. Phase 3: PK parameters for bemarituzumab, including, but not limited to, area under the concentration time curve (AUC), maximum observed concentration (Cmax), observed concentration at the end of a dose interval (Ctrough)
16. Phase 3: Anti-bemarituzumab antibody formation
17. Phase 3: - Duration of response DOR is defined as the time from the first documentation of objective response (as determined by investigator per RECIST v1.1) until the first documentation of disease progression or death due to any cause, whichever occurs

Investigational products

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

Test 1

Placebo 1

Auxiliary 5

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Amgen Inc.

Sponsor organisation

Amgen Inc.

Address

1 Amgen Center Drive

City

Thousand Oaks

Postcode

91320-1799

Country

United States

Scientific contact point

Organisation

Amgen Inc.

Contact name

Medical Information

Public contact point

Organisation

Amgen Inc.

Contact name

Medical Information

Third parties 9

Locations

12 EU/EEA countries · 124 investigational sites

By country

Investigational sites

Country notifications

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

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Serious breaches 2 · Art. 52 CTR

Results and documents

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

Documents 148 files

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

Application history

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