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

Advanced Cancer Clinical Trial

Official title:

Phase 1/2 Dose-Escalation and Expansion Study of FLX475 Alone and in Combination With Pembrolizumab in Advanced Cancer

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03674567
• Other study ID #: FLX475-02
• Secondary ID: KEYNOTE-877MK-34
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: September 25, 2018
• Est. completion date: January 2025

Study information

• Verified date: April 2024
• Source: RAPT Therapeutics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 323
• Est. completion date: January 2025
• Est. primary completion date: September 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Advanced Cancer
• Neoplasms

Intervention

Drug:
• FLX475
tablet
• pembrolizumab (KEYTRUDA®)
IV infusion

Locations

Country	Name	City	State
Australia	Austin Hospital	Heidelberg	Victoria
Australia	Linear Clinical Research Limited	Nedlands	Western Australia
Hong Kong	Queen Mary Hospital	High West
Hong Kong	Queen Mary Hospital - Lymphoma	High West
Hong Kong	Prince of Wales Hospital	Shatin
Korea, Republic of	Chungbuk National University Hospital	Chungbuk
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University	Seoul
Korea, Republic of	Severance Hospital, Yonsei University Health System	Seoul
Taiwan	Chi Mei Meidcal Center	Tainan
Taiwan	National Cheng Kung University Hospital	Tainan
Taiwan	National Taiwan University Hospital	Taipei
Taiwan	Taipei Veterans General Hospital	Taipei
Thailand	King Chulaongkorn Memorial Hospital	Bangkok
Thailand	Ramathibodi Hospital	Bangkok
United States	University of Michigan	Ann Arbor	Michigan
United States	Emory Winship Cancer Institute	Atlanta	Georgia
United States	Johns Hopkins University	Baltimore	Maryland
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	University of Chicago	Chicago	Illinois
United States	Mary Crowley Cancer Research Center	Dallas	Texas
United States	City of Hope	Duarte	California
United States	Banner MD Anderson Cancer Center	Gilbert	Arizona
United States	The University of Texas MD Anderson Cancer Center	Houston	Texas
United States	Carolina BioOncology Institute	Huntersville	North Carolina
United States	University of California, Los Angeles JCCC Clinical Research Unit	Los Angeles	California
United States	University of Louisville Hospital/James Graham Brown Cancer Center	Louisville	Kentucky
United States	Yale Cancer Center	New Haven	Connecticut
United States	New York Presbyterian Hospital-Columbia University Medical Center	New York	New York
United States	Comprehensive Hematology and Oncology, LLC	Saint Petersburg	Florida
United States	Quantum Santa Fe	Santa Fe	New Mexico
United States	University of Washington	Seattle	Washington
United States	Moffitt Cancer Center	Tampa	Florida
United States	Georgetown - Lombardi Comprehensive Cancer Center	Washington	District of Columbia

Sponsors (2)

Lead Sponsor	Collaborator
RAPT Therapeutics, Inc.	Merck Sharp & Dohme LLC

Countries where clinical trial is conducted

United States,  Australia,  Hong Kong,  Korea, Republic of,  Taiwan,  Thailand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Overall response rate in subjects treated with FLX475 as a single agent and in combination with pembrolizumab		Through study completion (approximately 2 years)