Neoplasms

Digestive System Diseases

All Conditions

Rare Diseases

Stomach Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Stomach Cancer

Micronutrients

All Drugs and Chemicals

Antineoplastic Agents

Vitamins

Leucovorin

Fluorouracil

Levoleucovorin

Oxaliplatin

Bemarituzumab

Antineoplastic Agents, Immunological

Folinic Acid

Participants received 6 mg/kg bemarituzumab administered every 2 weeks (Q2W) and mFOLFOX6 chemotherapy administered Q2W until unacceptable toxicity, disease progression, or death.

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.

Administered by intravenous infusion over approximately 30 minutes

Modified FOLFOX6 regimen consists of the following:

* Oxaliplatin 85 mg/m² IV infusion over 120 minutes
* Leucovorin 400 mg/m² IV infusion over 120 minutes, or 200 mg/m² levo-leucovorin if leucovorin is unavailable
* 5-fluorouracil (5-FU) 400 mg/m² bolus over approximately 5 minutes then 5-FU 2400 mg/m² as a continuous IV infusion over approximately 48 hours.

Modified FOLFOX6

The primary objective of the phase 1 portion of this study is to determine the recommended dose of bemarituzumab in combination with 5-fluorouracil, leucovorin and oxaliplatin (modified FOLFOX6) to use in the phase 2 portion of the trial.

Phase 1 is an open-label dose-escalation of bemarituzumab in combination with modified FOLFOX6 (mFOLFOX6). Eligible patients will have unresectable locally advanced or metastatic GI cancer of any type and be candidates to receive at least 2 doses of mFOLFOX6 chemotherapy. Phase 1 consists of 2 dosing cohorts of bemarituzumab in combination with mFOLFOX6 to determine the recommended dose of bemarituzumab in combination with mFOLFOX6 for the phase 2 portion of the study (see study record NCT03694522).

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

FIGHT: A Phase 3 Randomized, Double-Blind, Controlled Study Evaluating FPA144 and Modified FOLFOX6 in Patients With Previously Untreated Advanced Gastric and Gastroesophageal Cancer: Phase 2 Preceded by Dose Finding in Phase 1

A treatment-related adverse event (TRAE) is defined as an adverse event (AE) with an onset date on or after the date of first dose of study treatment, or an event present before treatment that worsened after treatment, and with an onset date prior to 28 days after the last date of dose, for which the investigator assessed as related to investigational product The investigator classified the severity of each AE using 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).

DLTs were defined as any of the following events considered by the investigator to be related to study drug:

* Absolute neutrophil count (ANC) \< 0.5 × 10⁹/L \> 5 days duration or febrile neutropenia.
* Platelets \< 25 × 10⁹/L or \< 50 × 10⁹/L with bleeding requiring medical intervention or for \> 3 days.
* Grade 4 anemia.
* Any Grade 2-3 ophthalmologic AE not resolving within 7 days.
* Any Grade 4 ophthalmologic AE.
* Any Grade 4 laboratory value.
* Any Grade 3 laboratory values that are not of clinical significance according to investigator and Sponsor agreement if they do not resolve within 72 hours.
* Aspartate aminotransferase/alanine aminotransferase (AST/ALT) ≥ 3× upper limit of normal (ULN) and concurrent total bilirubin ≥ 2× ULN not related to liver involvement with cancer.
* Any non-hematological AE ≥ Grade 3 (except nausea, vomiting, and diarrhea).
* Grade 3 nausea, vomiting or diarrhea not resolving with supportive care in 72 hours.
* Grade 4 nausea, vomiting or diarrhea.

Treatment-emergent adverse events are defined as adverse events (AEs) that started or worsened between the start of study drug and 28 days after permanent discontinuation of study drug.

A serious AE is defined as any untoward medical occurrence that at any dose:

* 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 the study treatment and each AE, and assessed the severity of each AE according to the guidelines provided in 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).

Ocular events associated with symptomatic corneal involvement and symptomatic and asymptomatic retinal involvement were events of special interest in this study.

Area under the observed concentration-time curve from the time of dosing to Day 14 (0-336h) calculated by log-linear trapezoidal approximation.

Postbaseline treatment induced antidrug antibody (ADA) positive is defined as participants with

* ADA negative at baseline and ADA positive at any postbaseline timepoint, or
* ADA positive at baseline and ADA positive with titer of at least 4-fold of the baseline titer at one or more postbaseline timepoint.

Five Prime Therapeutics, Inc.

Participants received 6 mg/kg bemarituzumab administered Q2W and mFOLFOX6 chemotherapy administered Q2W until unacceptable toxicity, disease progression, or death.

Bemarituzumab 6 mg/kg + mFOLFOX6

Bemarituzumab 15 mg/kg + mFOLFOX6

Total

Age, Continuous

Age, Customized

Sex: Female, Male

Ethnicity (NIH/OMB)

Race/Ethnicity, Customized

A scale to assess a patient's disease status.

* 0 = Fully active, able to carry out all pre-disease performance without restriction;
* 1 = Restricted in physically strenuous activity, ambulatory and able to carry out work of a light nature;
* 2 = Ambulatory and capable of all self-care, unable to carry out any work activities. Up and about \> 50% of waking hours;
* 3 = Capable of only limited self-care, confined to bed or chair \> 50% of waking hours;
* 4 = Completely disabled, confined to bed or chair;
* 5 = Dead.

Eastern Cooperative Oncology Group (ECOG) Performance Status

Anti-Cancer Treatment Prior to Enrollment

Study Director

All participants who received any portion of at least 1 dose of study treatment.

Number of Participants With Treatment-related Adverse Events ≥ Grade 2

DLT-evaluable population includes all participants enrolled in Phase 1 of the study who received at least 2 doses of bemarituzumab (except for Cohort 2 \[must have received 3 doses of bemarituzumab\]) and mFOLFOX6 and completed Cycles 1 and 2 of treatment, or who experienced a DLT in Cycle 1 or Cycle 2.

Number of Participants With Dose Limiting Toxicities (DLTs)

Any treatment-emergent adverse event (TEAE)

TEAE with Grade ≥ 3

TEAE related to any study drug

TEAE related to bemarituzumab

TEAE related to any agent of mFOLFOX6

TEAE with Grade ≥ 3 related to any study drug

Serious adverse event (SAE)

SAE related to any study drug

SAE related to bemarituzumab

SAE related to any agent of mFOLFOX6

TEAE of special interest: corneal/retina

TEAE of special interest: corneal/retina related to bemarituzumab

TEAE of special interest: corneal/retina leading to discontinuation of bemarituzumab

TEAE leading to discontinuation of bemarituzumab

TEAE leading to discontinuation of any agent of mFOLFOX6

TEAE leading to dose reduction of bemarituzumab

TEAE leading to dose reduction of any agent of mFOLFOX6

TEAE leading to death (Grade 5)

Number of Participants With Treatment-emergent Adverse Events

Cycle 1

Cycle 2

Participants who received bemarituzumab with available Cmax data

Maximum Observed Serum Concentration (Cmax) of Bemarituzumab

Participants who received bemarituzumab with available Ctrough data

Observed Serum Concentration of Bemarituzumab at the End of the Dose Interval (Ctrough)

Participants who received bemarituzumab with available AUC data

Area Under the Observed Concentration-time Curve From the Time of Dosing to Day 14 (AUC0-14)

Participants who received bemarituzumab with available half-life data

Terminal Half-life (t1/2) of Bemarituzumab

The ADA-evaluable analysis set includes all enrolled participants who received at least 1 dose of bemarituzumab and had at least 1 ADA sample drawn at any timepoint with available ADA data.

Number of Participants With Treatment Induced Anti-bemarituzumab Antibodies

Participants received 6 mg/kg bemarituzumab administered every 2 weeks (Q2W) and modified FOLFOX6 (mFOLFOX6) chemotherapy administered Q2W until unacceptable toxicity, disease progression, or death.

Spots Global Cancer Trial Database for A Study of Bemarituzumab (FPA144) Combined With Modified FOLFOX6 in Gastric/Gastroesophageal Cancer

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

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