FGFR2b overexpression

P1, N=74, Terminated, Amgen | Completed --> Terminated; Business decision not due to safety concerns

P1/2, N=80, Recruiting, Amgen | Phase classification: P1 --> P1/2

P1, N=180, Active, not recruiting, Amgen | Phase classification: P1b --> P1

P1, N=80, Recruiting, Amgen | Trial primary completion date: Nov 2026 --> Mar 2026

Phase III and Ib/III trials of the FGFR2-targeted antibody bemarituzumab for G/GEJ cancer overexpressing FGFR2b are ongoing based on the promising result in a phase II trial, especially in cases with an FGFR2b positivity of ≥ 10%...CLDN18.2 is expressed in some G/GEJ tumors but lacks oncogenic driver potential, and the CLDN18.2-targeted antibody zolbetuximab prolonged the survival of CLDN18.2-positive G/GEJ cancer patients in phase III trials...Similarly, targeting of nondriver molecules such as DKK1, TROP2, and CEACAM5 is under investigation in early-stage clinical trials. This shift in focus from target molecules with driver potential to markers for precise drug delivery should increase the number of possible targets in G/GEJ cancer.

P1, N=80, Recruiting, Amgen | Trial completion date: Sep 2027 --> Apr 2028 | Trial primary completion date: May 2026 --> Nov 2026

P1/2, N=303, Recruiting, Amgen | Trial completion date: Jul 2026 --> Jun 2027 | Trial primary completion date: Oct 2024 --> Sep 2025

In FGFR2b-positive advanced GC, the combination of bemarituzumab-mFOLFOX6 led to numerically longer median PFS and OS compared with mFOLFOX6 alone. Efficacy was more pronounced with FGFR2b overexpression in ≥ 10% of tumor cells. Confirmatory phase 3 trials are ongoing (NCT05052801, NCT05111626).

P1, N=80, Recruiting, Amgen | Phase classification: P1b --> P1 | N=30 --> 80

P1/2, N=303, Recruiting, Amgen | Phase classification: P1b/2 --> P1/2

P1b, N=180, Active, not recruiting, Amgen | Recruiting --> Active, not recruiting | Trial completion date: Mar 2026 --> Apr 2024 | Trial primary completion date: Mar 2025 --> Apr 2024

P1b, N=180, Recruiting, Amgen | Trial completion date: Oct 2025 --> Mar 2026 | Trial primary completion date: Oct 2024 --> Mar 2025

P1b, N=30, Recruiting, Amgen | Trial completion date: Mar 2025 --> Jan 2026 | Trial primary completion date: Dec 2023 --> Oct 2024

After 24 months of follow-up, patients with FGFR2b overexpression treated with bemarituzumab + mFOLFOX6 continued to show clinically meaningful outcomes over patients treated with placebo + mFOLFOX6; more pronounced efficacy was observed in patients with ≥10% of tumor cells with 2+/3+ FGFR2b IHC staining intensity. Randomized phase 3 trials focused on patients with ≥10% of tumor cells to confirm the observed clinical benefit of bemarituzumab are ongoing.

P1b, N=180, Recruiting, Amgen | Trial completion date: Aug 2025 --> Nov 2025

P1b, N=180, Recruiting, Amgen | N=108 --> 180 | Trial primary completion date: Feb 2024 --> Jul 2024

In this exploratory phase 2 study, despite no statistically significant improvement in progression-free survival, treatment with bemarituzumab showed promising clinical efficacy. Confirmatory phase 3 trials of bemarituzumab plus mFOLFOX6 powered to demonstrate statistical significance are being investigated in patients with previously untreated, FGFR2b-overexpressing, advanced gastric or gastro-oesophageal junction adenocarcinoma.

Adding bemarituzumab, a first-in-class, anti-FGFR2b monoclonal antibody to mFOLFOX6 improved outcomes, indicating FGFR2b as a promising therapeutic target...FGFR2b overlap with PD-L1 is shown in the table. Table: 384P Conclusions Over 20% of sqNSCLC tissue samples overexpress FGFR2b, making it a promising therapeutic target for agents such as bemarituzumab.

P3, N=516, Recruiting, Amgen | Trial completion date: Jan 2025 --> Aug 2025 | Trial primary completion date: Jan 2025 --> Aug 2025

P2, N=155, Completed, Five Prime Therapeutics, Inc. | Active, not recruiting --> Completed

P3, N=702, Ongoing, Amgen Inc.

P1b, N=108, Recruiting, Amgen | Trial primary completion date: Jul 2024 --> Feb 2024

P1b, N=108, Recruiting, Amgen | Not yet recruiting --> Recruiting | Trial completion date: Feb 2025 --> Jul 2025 | Trial primary completion date: Feb 2024 --> Jul 2024

P1b, N=702, Recruiting, Amgen | Not yet recruiting --> Recruiting

P3, N=516, Recruiting, Amgen | Not yet recruiting --> Recruiting

P1b, N=108, Not yet recruiting, Amgen

MODULE 1: Current and Future Front-Line Management of Advanced Gastric and Gastroesophageal Junction (GEJ) Cancer Available efficacy and safety results from the Phase III CheckMate 649 study comparing first-line nivolumab in combination with chemotherapy or ipilimumab to chemotherapy alone for advanced gastric/GEJ adenocarcinoma; FDA approval and patient selection for up-front nivolumab/chemotherapy Mechanism of action of sintilimab; recently presented results from the Phase III ORIENT-16 trial comparing sintilimab with chemotherapy to chemotherapy alone as first-line treatment Biologic rationale for targeting claudin 18.2 in gastric/GEJ cancers; mechanism of antitumor activity of zolbetuximab Available efficacy and safety findings with first-line zolbetuximab/chemotherapy in patients with advanced claudin 18.2-positive gastric/GEJ adenocarcinoma; ongoing Phase III SPOTLIGHT and GLOW studies Frequency of FGFR2b overexpression in gastroesophageal cancers; mechanism of action of bemarituzumab Major efficacy and safety data from the Phase II FIGHT trial evaluating bemarituzumab/chemotherapy versus chemotherapy alone as first-line therapy for patients with FGFR2b-positive metastatic gastric/GEJ cancer; FDA breakthrough therapy designation MODULE 2: Contemporary Management of HER2-Positive Advanced Gastric and GEJ Cancer Principal outcomes from the Phase III KEYNOTE-811 trial supporting the FDA approval of first-line pembrolizumab/trastuzumab/chemotherapy for metastatic HER2-positive disease Updated results, including overall survival outcomes, from the Phase II DESTINY-Gastric01 study of trastuzumab deruxtecan (T-DXd) for patients with progressive HER2-positive gastric/GEJ cancer FDA approval of T-DXd for patients with HER2-positive gastric/GEJ cancer who have previously received a trastuzumab-based regimen; optimal incorporation into routine practice Recently presented efficacy and safety findings from the Phase II DESTINY-Gastric02 trial evaluating T-DXd in Western patients with HER2-positive gastric/GEJ cancer previously treated with a trastuzumab-based regimen Ongoing studies with T-DXd in earlier lines of treatment and/or in combination with other systemic therapies MODULE 3: Selection and Sequencing of Therapy for Relapsed Gastric and GEJ Cancer Optimal integration of ramucirumab into current clinical algorithms for metastatic gastric/GEJ cancer Available data with and ongoing investigation of novel ramucirumab-combination regimens Clinical research supporting the use of TAS-102 for heavily pretreated metastatic gastric/GEJ cancer; patient selection for treatment with TAS-102 Current role, if any, of anti-PD-1 monotherapy for patients with recurrent metastatic gastric/GEJ cancer; clinical implications of the voluntary withdrawal of third-line pembrolizumab Other promising agents and strategies under investigation for advanced gastric/GEJ cancer MODULE 4: Key Findings Informing the Treatment of Localized and Advanced Esophageal Cancer Design, eligibility criteria and primary findings from the Phase III KEYNOTE-590 study leading to the FDA approval of first-line pembrolizumab/chemotherapy for advanced esophageal and GEJ cancer; patient selection for this approach Major findings from the Phase III CheckMate 648 study evaluating nivolumab/chemotherapy, nivolumab/ipilimumab and chemotherapy alone for patients with unresectable advanced or metastatic squamous cell carcinoma of the esophagus Available Phase III clinical trial findings (eg, JUPITER-06, ORIENT-15) with investigational anti-PD-1 antibodies with chemotherapy as first-line treatment for esophageal squamous cell carcinoma Key efficacy and safety outcomes from the Phase III CheckMate 577 study of adjuvant nivolumab for patients with resected esophageal or GEJ cancer; recent FDA approval and appropriate integration into management algorithms

P3, N=516, Ongoing, Amgen Inc.

P1b, N=702, Not yet recruiting, Amgen

The PK data in cynomolgus monkeys were used to project bemarituzumab linear PK in humans, which were consistent with the observed human Phase 1 data. These key nonclinical studies facilitated the successful advancement of bemarituzumab into the clinic.

P3, N=516, Not yet recruiting, Amgen

No covariate had a clinically meaningful impact on bemarituzumab exposure. These results indicate that dose adjustment of bemarituzumab is not necessary, based on the aforementioned covariates, for a future phase 3 trial in gastric and gastroesophageal junction adenocarcinoma population with FGFR2b overexpression in combination with mFOLFOX6.

P2, N=155, Active, not recruiting, Five Prime Therapeutics, Inc. | Trial completion date: Dec 2021 --> May 2022 | Trial primary completion date: Mar 2021 --> Sep 2020

P2, N=155, Active, not recruiting, Five Prime Therapeutics, Inc. | Trial completion date: Jul 2024 --> Dec 2021 | Trial primary completion date: Jul 2022 --> Mar 2021