Trial Outcomes & Findings for A Study of Bemarituzumab (FPA144) Combined With Modified FOLFOX6 (mFOLFOX6) in Gastric/Gastroesophageal Junction Cancer (NCT NCT03694522)

Last Updated: 2024-02-28

Results Overview

PFS was defined as time from randomization until the date of radiographic disease progression based on investigator assessment using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 or death from any cause, whichever came first. PFS was analyzed using Kaplan-Meier methods. Participants with no progression or death, or who started new anticancer therapy before documented progression or death without documented progression, or who had ≥ 2 consecutive missing tumor assessments before documented progression or death without documented progression were censored on the date of last adequate tumor assessment. Participants with no baseline tumor assessment, were censored at the date of randomization. The primary efficacy analysis was pre-specified to be conducted after at least 84 PFS events were observed.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

155 participants

Primary outcome timeframe

From randomization until the primary analysis data cut-off date of 23 September 2020; median time on follow-up was 10.9 months.

Results posted on

2024-02-28

Participant Flow

Study FPA144-004 was a Phase 1/2 study. Phase 1 was a safety run-in to determine the recommended dose of bemarituzumab to be administered in combination with a fixed dose of modified FOLFOX 6 (mFOLFOX6) chemotherapy regimen in the phase 2 part of the study. Phase 1 study details and results are reported separately (NCT03343301); Phase 2 study results are reported below.

Participants were randomized equally to one of two treatment groups stratified based on the following factors: * Geographic region: United States/European Union, China, or Rest of Asia * Prior treatment status: de novo (no prior adjuvant/neo-adjuvant therapy) or prior adjuvant/neo-adjuvant therapy * Administration of a single dose of mFOLFOX6 prior to enrollment: Yes or No.

Participant milestones

Participant milestones
Measure	Bemarituzumab + mFOLFOX6 Participants received 15 mg/kg bemarituzumab administered every 2 weeks (Q2W) with a single additional bemarituzumab 7.5 mg/kg dose on cycle 1 day 8. Participants also received modified FOLFOX (mFOLFOX6) chemotherapy administered Q2W. Treatment continued until unacceptable toxicity, disease progression, or death.	Placebo + mFOLFOX6 Participants received placebo for bemarituzumab administered Q2W with a single additional placebo dose on cycle 1 day 8. Participants also received mFOLFOX6 chemotherapy administered Q2W. Treatment continued until unacceptable toxicity, disease progression, or death.
Overall Study STARTED	77	78
Overall Study Received Any Study Treatment	76	77
Overall Study COMPLETED	15	12
Overall Study NOT COMPLETED	62	66

Reasons for withdrawal

Reasons for withdrawal
Measure	Bemarituzumab + mFOLFOX6 Participants received 15 mg/kg bemarituzumab administered every 2 weeks (Q2W) with a single additional bemarituzumab 7.5 mg/kg dose on cycle 1 day 8. Participants also received modified FOLFOX (mFOLFOX6) chemotherapy administered Q2W. Treatment continued until unacceptable toxicity, disease progression, or death.	Placebo + mFOLFOX6 Participants received placebo for bemarituzumab administered Q2W with a single additional placebo dose on cycle 1 day 8. Participants also received mFOLFOX6 chemotherapy administered Q2W. Treatment continued until unacceptable toxicity, disease progression, or death.
Overall Study Withdrawal by Subject	8	10
Overall Study Physician Decision	53	54
Overall Study Other	1	1
Overall Study Lost to Follow-up	0	1

Baseline Characteristics

A Study of Bemarituzumab (FPA144) Combined With Modified FOLFOX6 (mFOLFOX6) in Gastric/Gastroesophageal Junction Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Bemarituzumab + mFOLFOX6 n=77 Participants Participants received 15 mg/kg bemarituzumab administered Q2W with a single additional bemarituzumab 7.5 mg/kg dose on cycle 1 day 8. Participants also received mFOLFOX6 chemotherapy administered Q2W. Treatment continued until unacceptable toxicity, disease progression, or death.	Placebo + mFOLFOX6 n=78 Participants Participants received placebo for bemarituzumab administered Q2W with a single additional placebo dose on cycle 1 day 8. Participants also received mFOLFOX6 chemotherapy administered Q2W. Treatment continued until unacceptable toxicity, disease progression, or death.	Total n=155 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=113 Participants	0 Participants n=163 Participants	0 Participants n=160 Participants
Age, Categorical Between 18 and 65 years	58 Participants n=113 Participants	53 Participants n=163 Participants	111 Participants n=160 Participants
Age, Categorical >=65 years	19 Participants n=113 Participants	25 Participants n=163 Participants	44 Participants n=160 Participants
Age, Continuous	58.0 years STANDARD_DEVIATION 11.11 • n=113 Participants	59.1 years STANDARD_DEVIATION 12.04 • n=163 Participants	58.5 years STANDARD_DEVIATION 11.56 • n=160 Participants
Sex: Female, Male Female	25 Participants n=113 Participants	19 Participants n=163 Participants	44 Participants n=160 Participants
Sex: Female, Male Male	52 Participants n=113 Participants	59 Participants n=163 Participants	111 Participants n=160 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=113 Participants	3 Participants n=163 Participants	5 Participants n=160 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	74 Participants n=113 Participants	75 Participants n=163 Participants	149 Participants n=160 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=113 Participants	0 Participants n=163 Participants	1 Participants n=160 Participants
Race/Ethnicity, Customized Asian	45 Participants n=113 Participants	44 Participants n=163 Participants	89 Participants n=160 Participants
Race/Ethnicity, Customized Black or African American	0 Participants n=113 Participants	1 Participants n=163 Participants	1 Participants n=160 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 Participants n=113 Participants	1 Participants n=163 Participants	1 Participants n=160 Participants
Race/Ethnicity, Customized White	30 Participants n=113 Participants	31 Participants n=163 Participants	61 Participants n=160 Participants
Race/Ethnicity, Customized Other	2 Participants n=113 Participants	1 Participants n=163 Participants	3 Participants n=160 Participants
Geographic Region United States / European Union	32 Participants n=113 Participants	34 Participants n=163 Participants	66 Participants n=160 Participants
Geographic Region China	14 Participants n=113 Participants	13 Participants n=163 Participants	27 Participants n=160 Participants
Geographic Region Rest of Asia	31 Participants n=113 Participants	31 Participants n=163 Participants	62 Participants n=160 Participants
Prior Treatment Status Prior adjuvant/neo-adjuvant therapy	14 Participants n=113 Participants	13 Participants n=163 Participants	27 Participants n=160 Participants
Prior Treatment Status No prior adjuvant/neo-adjuvant therapy	63 Participants n=113 Participants	65 Participants n=163 Participants	128 Participants n=160 Participants
Administration of a Single Dose of mFOLFOX6 Prior to Enrollment Yes	35 Participants n=113 Participants	36 Participants n=163 Participants	71 Participants n=160 Participants
Administration of a Single Dose of mFOLFOX6 Prior to Enrollment No	42 Participants n=113 Participants	42 Participants n=163 Participants	84 Participants n=160 Participants
Site of Primary Cancer Gastric cancer	66 Participants n=113 Participants	71 Participants n=163 Participants	137 Participants n=160 Participants
Site of Primary Cancer Gastroesophageal junction cancer	11 Participants n=113 Participants	7 Participants n=163 Participants	18 Participants n=160 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status 0 (Fully active)	25 Participants n=113 Participants	28 Participants n=163 Participants	53 Participants n=160 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status 1 (Restricted activity but ambulatory)	52 Participants n=113 Participants	50 Participants n=163 Participants	102 Participants n=160 Participants

PRIMARY outcome

Timeframe: From randomization until the primary analysis data cut-off date of 23 September 2020; median time on follow-up was 10.9 months.

Population: Intent-to-treat population

Outcome measures

Outcome measures
Measure	Bemarituzumab + mFOLFOX6 n=77 Participants Participants received 15 mg/kg bemarituzumab administered Q2W with a single additional bemarituzumab 7.5 mg/kg dose on cycle 1 day 8. Participants also received mFOLFOX6 chemotherapy administered Q2W. Treatment continued until unacceptable toxicity, disease progression, or death.	Placebo + mFOLFOX6 n=78 Participants Participants received placebo for bemarituzumab administered Q2W with a single additional placebo dose on cycle 1 day 8. Participants also received mFOLFOX6 chemotherapy administered Q2W. Treatment continued until unacceptable toxicity, disease progression, or death.
Progression-Free Survival (PFS)	9.5 months Interval 7.3 to 12.9	7.4 months Interval 5.8 to 8.4

SECONDARY outcome

Timeframe: From randomization until the primary analysis data cut-off date of 23 September 2020; median time on follow-up was 10.9 months.

Population: Intent-to-treat population

OS is defined as time from randomization until death from any cause. Participants who were lost to follow-up or did not have a date of death were censored at the last date that they were known to be alive. Participants with confirmed death or alive status after the data cutoff date were censored at the data cutoff date. Median OS was estimated using a Kaplan-Meier analysis.

Outcome measures

Outcome measures
Measure	Bemarituzumab + mFOLFOX6 n=77 Participants Participants received 15 mg/kg bemarituzumab administered Q2W with a single additional bemarituzumab 7.5 mg/kg dose on cycle 1 day 8. Participants also received mFOLFOX6 chemotherapy administered Q2W. Treatment continued until unacceptable toxicity, disease progression, or death.	Placebo + mFOLFOX6 n=78 Participants Participants received placebo for bemarituzumab administered Q2W with a single additional placebo dose on cycle 1 day 8. Participants also received mFOLFOX6 chemotherapy administered Q2W. Treatment continued until unacceptable toxicity, disease progression, or death.
Overall Survival (OS)	NA months Interval 13.8 to Could not be estimated due to the low number of events	12.9 months Interval 9.1 to 15.0

SECONDARY outcome

Timeframe: Tumor assessments were performed every 8 weeks until 12 months and then every 12 weeks thereafter until disease progression or additional anticancer therapy was initiated; the median duration of follow-up time was 10.9 months.

Population: Intent-to-treat population

Tumor response assessment was performed by the investigator per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 guidelines. ORR is defined as the percentage of participants who achieved a best overall response (BOR) of either complete response (CR) or partial response (PR) based on investigator assessment of tumor lesions per RECIST v1.1. CR was defined as the disappearance of all lesions except lymph node short axis \< 10 mm; PR was defined as a ≥ 30% reduction in sum of diameters in target lesions.

Outcome measures

Outcome measures
Measure	Bemarituzumab + mFOLFOX6 n=77 Participants Participants received 15 mg/kg bemarituzumab administered Q2W with a single additional bemarituzumab 7.5 mg/kg dose on cycle 1 day 8. Participants also received mFOLFOX6 chemotherapy administered Q2W. Treatment continued until unacceptable toxicity, disease progression, or death.	Placebo + mFOLFOX6 n=78 Participants Participants received placebo for bemarituzumab administered Q2W with a single additional placebo dose on cycle 1 day 8. Participants also received mFOLFOX6 chemotherapy administered Q2W. Treatment continued until unacceptable toxicity, disease progression, or death.
Overall Response Rate (ORR)	46.8 percentage of participants Interval 35.3 to 58.5	33.3 percentage of participants Interval 23.1 to 44.9

SECONDARY outcome

Timeframe: From first dose of study drug to 28 days after last dose of study drug. Actual median (min, max) duration of treatment emergent period was 29 (4.1, 157) weeks in the bemarituzumab + mFOLFOX6 group and 28 (4.3, 133) weeks in the placebo + mFOLFOX6 group.

Population: Safety population includes all participants who received any portion of at least 1 dose of study treatment (bemarituzumab + mFOLFOX6 or placebo + mFOLFOX6).

TEAEs are defined as adverse events (AEs) that started or worsened from the start of study drug to 28 days after permanent discontinuation of study drug. A serious AE is defined as any untoward medical occurrence that: * Resulted in death; * Was life-threatening; * Required inpatient hospitalization or prolongation of existing hospitalization; * Resulted in persistent or significant disability or incapacity; * Was a congenital anomaly or birth defect. The investigator assessed the causality/relationship between study treatment and each AE, and assessed the severity of each AE according to the National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI-CTCAE), version 5.0 on a scale from mild (Grade 1), moderate (Grade 2), severe (Grade 3), life-threatening (Grade 4), or death due to the AE (Grade 5). Cornea and retina AEs were defined by Standardized Medical Dictionary for Regulatory Activities Queries (SMQs) of corneal disorders and retinal disorders (broad).

Outcome measures

Outcome measures
Measure	Bemarituzumab + mFOLFOX6 n=76 Participants Participants received 15 mg/kg bemarituzumab administered Q2W with a single additional bemarituzumab 7.5 mg/kg dose on cycle 1 day 8. Participants also received mFOLFOX6 chemotherapy administered Q2W. Treatment continued until unacceptable toxicity, disease progression, or death.	Placebo + mFOLFOX6 n=77 Participants Participants received placebo for bemarituzumab administered Q2W with a single additional placebo dose on cycle 1 day 8. Participants also received mFOLFOX6 chemotherapy administered Q2W. Treatment continued until unacceptable toxicity, disease progression, or death.
Number of Participants With Treatment-emergent Adverse Events (TEAEs) TEAE with Grade ≥ 3	63 Participants	58 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) TEAE with Grade ≥ 3 related to any study drug	57 Participants	48 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Any treatment-emergent adverse event (TEAE)	76 Participants	76 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) TEAE related to any study drug	72 Participants	73 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Serious adverse event (SAE)	26 Participants	28 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) SAE related to any study drug	11 Participants	15 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) TEAE leading to discontinuation of bemarituzumab/placebo	31 Participants	4 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) TEAE leading to discontinuation of any component of mFOLFOX6	35 Participants	29 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) TEAE leading to dose reduction of bemarituzumab/placebo	9 Participants	7 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) TEAE leading to dose reduction of any agent of mFOLFOX6	48 Participants	44 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) TEAE leading to dose delay of bemarituzumab/placebo	51 Participants	41 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) TEAE leading to dose delay of any agent of mFOLFOX6	54 Participants	44 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) TEAE leading to Infusion interruption of bemarituzumab/placebo	3 Participants	3 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) TEAE leading to infusion interruption of any agent of mFOLFOX6	10 Participants	17 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Corneal disorders (SMQ) TEAE	51 Participants	8 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Corneal disorders (SMQ) TEAE with Grade ≥ 3	21 Participants	0 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Corneal disorders (SMQ) TEAE related to bemarituzumab/placebo	46 Participants	7 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Corneal disorder (SMQ) TEAE leading to discontinuation of bemarituzumab/placebo	24 Participants	0 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Retinal disorders (SMQ) TEAE	18 Participants	7 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Retinal disorders (SMQ) TEAE with Grade ≥ 3	1 Participants	0 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Retinal disorders (SMQ) TEAE related to bemarituzumab/placebo	12 Participants	5 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Retinal disorder (SMQ) TEAE leading to discontinuation of bemarituzumab/placebo	2 Participants	0 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) TEAE leading to death (Grade 5)	5 Participants	4 Participants

POST_HOC outcome

Timeframe: From randomization until 28 February 2021; median time on follow-up was 12.5 months.

Population: Intent-to-treat population

Outcome measures

Outcome measures
Measure	Bemarituzumab + mFOLFOX6 n=77 Participants Participants received 15 mg/kg bemarituzumab administered Q2W with a single additional bemarituzumab 7.5 mg/kg dose on cycle 1 day 8. Participants also received mFOLFOX6 chemotherapy administered Q2W. Treatment continued until unacceptable toxicity, disease progression, or death.	Placebo + mFOLFOX6 n=78 Participants Participants received placebo for bemarituzumab administered Q2W with a single additional placebo dose on cycle 1 day 8. Participants also received mFOLFOX6 chemotherapy administered Q2W. Treatment continued until unacceptable toxicity, disease progression, or death.
Overall Survival - Updated Analysis	19.2 months Interval 13.6 to Could not be estimated due to the low number of events at the time of the data cut.	13.5 months Interval 9.3 to 15.9

Adverse Events

Bemarituzumab + mFOLFOX6

Serious events: 26 serious events

Other events: 75 other events

Deaths: 53 deaths

Placebo + mFOLFOX6

Serious events: 28 serious events

Other events: 75 other events

Deaths: 55 deaths

Serious adverse events

Other adverse events

Additional Information

Study Director

Amgen

Phone: 866-572-6436

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The CTA generally does not restrict an investigator's discussion of trial results after completion. Amgen has limited time to review material discussing trial results (up to 45 days and possible extension). Amgen may remove confidential information, but authors have final control/approval of content. For multicenter studies, PI agrees not to publish results before first multi-center publication for at least 18 mo after study completion at all sites \& all analyses of data resulting from Study.
Publication restrictions are in place

Restriction type: OTHER