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

NCT03343301 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: FPA144-004 Phase 1
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 7

Brief Summary

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.

Conditions

Gastrointestinal Cancer; Gastrointestinal Cancer Metastatic; Gastric Cancer

Keywords

gastrointestinal cancer

Outcome Measures

Primary Outcomes (2)

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

  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).

  From first dose of study drug up to 28 days after last dose; Actual median (min, max) duration of treatment emergent period was 19.3 (12.3, 22.3) weeks in the bemarituzumab 6 mg/kg group and 19.4 (4.0, 35.4) weeks in the bemarituzumab 15 mg/kg group.

• Number of Participants With Dose Limiting Toxicities (DLTs)

  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.

  28 days

Secondary Outcomes (6)

• Number of Participants With Treatment-emergent Adverse Events

  From first dose of study drug up to 28 days after last dose; Actual median (min, max) duration of the treatment emergent period was 19.3 (12.3, 22.3) weeks in the bemarituzumab 6 mg/kg group and 19.4 (4.0, 35.4) weeks in the bemarituzumab 15 mg/kg group.

• Maximum Observed Serum Concentration (Cmax) of Bemarituzumab

  Cycle 1 day 1 at predose, 0.25, 4, 48, and 168 hours after end of infusion, and for participants in Cohort 2 day 8 at 0.25 and 4 hours end of infusion; Cycle 2 day 1 at predose, 0.25 and 48 hours after end of infusion.

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

  Cycle 1 day 14 predose for cohort 1 and day 8 predose for cohort 2; Cycle 2 day 14 predose

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

  Cycle 1 day 1 at predose, 0.25, 4, 48, and 168 hours after end of infusion, and for participants in Cohort 2 day 8 at 0.25 and 4 hours after the end of infusion.

• Terminal Half-life (t1/2) of Bemarituzumab

  Cycle 1 day 1 at predose, 0.25, 4, 48, and 168 hours after end of infusion, and for participants in Cohort 2 day 8 at 0.25 and 4 hours after end of infusion.

Study Arms (2)

Bemarituzumab 6 mg/kg + mFOLFOX6

EXPERIMENTAL

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

Biological: Bemarituzumab; Drug: Modified FOLFOX6

Bemarituzumab 15 mg/kg + mFOLFOX6

EXPERIMENTAL

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.

Biological: Bemarituzumab; Drug: Modified FOLFOX6

Interventions

Bemarituzumab BIOLOGICAL

Administered by intravenous infusion over approximately 30 minutes

Also known as: FPA144

Bemarituzumab 15 mg/kg + mFOLFOX6; Bemarituzumab 6 mg/kg + mFOLFOX6

Modified FOLFOX6 DRUG

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.

Also known as: mFOLFOX6

Bemarituzumab 15 mg/kg + mFOLFOX6; Bemarituzumab 6 mg/kg + mFOLFOX6

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Disease that is unresectable, locally advanced, or metastatic (not amendable to curative therapy)
• Understand and sign an Institutional Review Board (IRB)/Independent Ethics Committee (IEC)-approved informed consent form (ICF) prior to any study-specific evaluation
• Life expectancy of at least 3 months in the opinion of the investigator
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
• Age ≥ 18 years at the time the ICF is signed
• In sexually active patients (women of childbearing potential and males), willingness to use 2 effective methods of contraception, of which 1 must be a physical barrier method (condom, diaphragm, or cervical/vault cap) until 6 months after the last dose of FPA144. Other effective forms of contraception include:
• Permanent sterilization (hysterectomy and/or bilateral oophorectomy, or bilateral tubal ligation with surgery, or vasectomy) at least 6 months prior to Screening
• Women of childbearing potential who are on stable oral contraceptive therapy or intrauterine or implant device for at least 90 days prior to the study, or abstain from sexual intercourse as a way of living
• Adequate hematological and biological function, confirmed by the following laboratory values within 96 hours prior to enrollment:
• Bone Marrow Function
• Absolute neutrophil count (ANC) ≥ 1.5 × 10\^9/L
• Platelets ≥ 100 × 10\^9/L
• Hemoglobin ≥ 9 g/dL
• Hepatic Function
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \< 3 × upper limit of normal (ULN); if liver metastases, then \< 5 × ULN

You may not qualify if:

• Untreated or symptomatic central nervous system (CNS) metastases (CNS imaging not required). Patients with asymptomatic CNS metastases are eligible provided they have been clinically stable for at least 4 weeks and do not require intervention such as surgery, radiation, or any corticosteroid therapy for management of symptoms related to CNS disease
• Impaired cardiac function or clinically significant cardiac disease, including any of the following (Criteria a through g):
• Unstable angina pectoris ≤ 6 months prior to enrollment
• Acute myocardial infarction ≤ 6 months prior to enrollment
• New York Heart Association Class II-IV congestive heart failure
• Uncontrolled hypertension (as defined as ≥ 160/90 despite optimal medical management)
• Uncontrolled cardiac arrhythmias requiring anti-arrhythmic therapy other than beta blockers or digoxin
• Active coronary artery disease
• Fridericia's corrected QT interval (QTcF) ≥ 480
• Peripheral sensory neuropathy ≥ Common Terminology Criteria for Adverse Events (CTCAE) Grade 2
• Active infection requiring systemic treatment or any uncontrolled infection ≤ 14 days prior to enrollment
• Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness, or known active or chronic hepatitis B or C infection
• History of interstitial lung disease (e.g., pneumonitis or pulmonary fibrosis)
• Evidence or history of bleeding diathesis or coagulopathy
• Radiotherapy ≤ 28 days of enrollment. Patients must be recovered from all acute radiotherapy-related toxicities. No radiopharmaceuticals (strontium, samarium) within 8 weeks of enrollment

Sponsors & Collaborators

• Five Prime Therapeutics, Inc.: lead

Study Sites (7)

The University of Arizona Cancer Center

Tucson, Arizona, 85724, United States

Location

Marin Cancer Care

Greenbrae, California, 94904, United States

Location

Innovative Clinical Research Institute

Whittier, California, 90603, United States

Location

The University of Chicago Medical Center

Chicago, Illinois, 90603, United States

Location

Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Wilmont Cancer Institute

Rochester, New York, 14642, United States

Location

Tennessee Cancer Specialists

Knoxville, Tennessee, 37909, United States

Location

MeSH Terms

Conditions

Gastrointestinal Neoplasms; Stomach Neoplasms

Interventions

bemarituzumab

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases

Results Point of Contact

• Title: Study Director
• Organization: Amgen

medinfo@amgen.com

866-572-6436

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 7, 2017
• First Posted: November 17, 2017
• Study Start: November 30, 2017
• Primary Completion: January 31, 2019
• Study Completion: January 31, 2019
• Last Updated: February 28, 2024
• Results First Posted: January 27, 2023

Record last verified: 2024-02

Locations

US (7)