Dose Escalation and Expansion Study of FLX475 Monotherapy and in Combination with Pembrolizumab

Phase 1

Completed

• Conditions: Advanced Cancer
• Interventions: Drug: FLX475; Drug: pembrolizumab (KEYTRUDA®)

• Registration Number: NCT03674567
• Lead Sponsor: RAPT Therapeutics, Inc.

Brief Summary

This clinical trial is a Phase 1/2, open-label, sequential-group, dose-escalation and cohort expansion study to determine the safety and preliminary anti-tumor activity of FLX475 as monotherapy and in combination with pembrolizumab.

The study will be conducted in 2 parts, a dose-escalation phase (Part 1) and a cohort expansion phase (Part 2). In Part 1 of the study, subjects will be enrolled in sequential cohorts treated with successively higher doses of FLX475 as monotherapy or in combination with pembrolizumab. In Part 2 of the study, subjects will be initially enrolled in Stage 1 of parallel expansion cohorts of FLX475 as monotherapy or in combination with pembrolizumab.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2018-09-14
• Study First Submitted QC: 2018-09-14
• Study First Posted: 2018-09-17
• Study Start: 2018-09-25
• Primary Completion: 2024-12-31
• Study Completion: 2024-12-31
• Status Verified: 2025-01
• Last Update Submitted: 2025-01-21
• Last Update Posted: 2025-01-24

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 323

Inclusion Criteria

• Documented advanced or metastatic cancer ineligible for standard therapies with one of the following histologies

  • Dose Escalation: non-small cell lung cancer, head and neck squamous cell carcinoma, nasopharyngeal carcinoma, metastatic triple negative breast cancer, urothelial carcinoma, gastric cancer, esophageal carcinoma, cervical cancer, classical Hodgkin lymphoma
  • Dose Expansion: nasopharyngeal carcinoma, lymphoma, head and neck squamous cell carcinoma, cervical cancer, non-small cell lung cancer, triple-negative breast cancer

• Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1

• Evaluable disease at baseline (at least one measurable target lesion by imaging for expansion cohorts)

• Tumor available for biopsy

Exclusion Criteria

• History of allergy or severe hypersensitivity to biologic agents
• History of Grade 3-4 immune-related adverse events leading to discontinuation of prior immuno-oncology treatment
• Active autoimmune disease or serious autoimmune disease within past 2 years requiring systemic therapy
• History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, (non-infectious) pneumonitis that required steroids, or symptoms of active pneumonitis
• Prior allogeneic hematopoietic stem cell transplant within 5 years, or prior allogeneic organ transplant
• Active graft-versus-host disease

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Part 1b: Combination Dose Escalation	pembrolizumab (KEYTRUDA®)	Eligible subjects will be enrolled in sequential cohorts treated with successively higher doses of FLX475 in combination with pembrolizumab.
Part 2b: Combination Expansion Cohorts	pembrolizumab (KEYTRUDA®)	Eligible subjects will be initially enrolled in Stage 1 of parallel expansion cohorts of FLX475 in combination with pembrolizumab; additional subjects in each cohort may be enrolled in Stage 2.
Part 1b: Combination Dose Escalation	FLX475	Eligible subjects will be enrolled in sequential cohorts treated with successively higher doses of FLX475 in combination with pembrolizumab.
Part 2a: Monotherapy Expansion Cohorts	FLX475	Eligible subjects will be initially enrolled in Stage 1 of parallel expansion cohorts of FLX475 as monotherapy; additional subjects in each cohort may be enrolled in Stage 2.
Part 2b: Combination Expansion Cohorts	FLX475	Eligible subjects will be initially enrolled in Stage 1 of parallel expansion cohorts of FLX475 in combination with pembrolizumab; additional subjects in each cohort may be enrolled in Stage 2.
Part 1a: Monotherapy Dose Escalation	FLX475	Eligible subjects will be enrolled in sequential cohorts treated with successively higher doses of FLX475 as monotherapy.

Primary Outcome Measures

Name	Time	Method
Safety and tolerability of FLX475 as a single agent and in combination with pembrolizumab measured by the incidence of adverse events, including dose-limiting toxicities and maximum tolerated dose	Approximately 18 weeks
Overall response rate in subjects treated with FLX475 as a single agent and in combination with pembrolizumab	Through study completion (approximately 2 years)

Trial Locations

Locations (35)

Banner MD Anderson Cancer Center; 🇺🇸 Gilbert, Arizona, United States

City of Hope; 🇺🇸 Duarte, California, United States

University of California, Los Angeles JCCC Clinical Research Unit; 🇺🇸 Los Angeles, California, United States

Yale Cancer Center; 🇺🇸 New Haven, Connecticut, United States

Georgetown - Lombardi Comprehensive Cancer Center; 🇺🇸 Washington, District of Columbia, United States

Comprehensive Hematology and Oncology, LLC; 🇺🇸 Saint Petersburg, Florida, United States

Moffitt Cancer Center; 🇺🇸 Tampa, Florida, United States

Emory Winship Cancer Institute; 🇺🇸 Atlanta, Georgia, United States

University of Chicago; 🇺🇸 Chicago, Illinois, United States

University of Louisville Hospital/James Graham Brown Cancer Center; 🇺🇸 Louisville, Kentucky, United States

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