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

• ClinicalTrials.gov Identifier: NCT03674567
• Recruitment Status: Active, not recruiting
• First Posted: September 17, 2018
• Last Update Posted: April 16, 2024
• Sponsor: RAPT Therapeutics, Inc.
• Collaborator: Merck Sharp & Dohme LLC
• Information provided by (Responsible Party): RAPT Therapeutics, Inc.

Tracking Information

• First Submitted Date: September 14, 2018
• First Posted Date: September 17, 2018
• Last Update Posted Date: April 16, 2024
• Actual Study Start Date: September 25, 2018
• Estimated Primary Completion Date: September 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 14, 2018)

• 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 [ Time Frame: Approximately 18 weeks ]
• Overall response rate in subjects treated with FLX475 as a single agent and in combination with pembrolizumab [ Time Frame: Through study completion (approximately 2 years) ]

• Original Primary Outcome Measures: Same as current
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Dose Escalation and Expansion Study of FLX475 Monotherapy and in Combination With Pembrolizumab
• Official Title: Phase 1/2 Dose-Escalation and Expansion Study of FLX475 Alone and in Combination With Pembrolizumab in Advanced Cancer

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 Provided
• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: Non-Randomized; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Advanced Cancer

Intervention

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

Study Arms

• Experimental: Part 1a: Monotherapy Dose Escalation
  Eligible subjects will be enrolled in sequential cohorts treated with successively higher doses of FLX475 as monotherapy.
  Intervention: Drug: FLX475
• Experimental: Part 1b: Combination Dose Escalation
  Eligible subjects will be enrolled in sequential cohorts treated with successively higher doses of FLX475 in combination with pembrolizumab.
  Interventions:

  • Drug: FLX475
  • Drug: pembrolizumab (KEYTRUDA®)
• Experimental: Part 2a: Monotherapy Expansion Cohorts
  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.
  Intervention: Drug: FLX475
• Experimental: Part 2b: Combination Expansion Cohorts
  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.
  Interventions:

  • Drug: FLX475
  • Drug: pembrolizumab (KEYTRUDA®)

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: March 26, 2024): 323
• Original Estimated Enrollment (submitted: September 14, 2018): 375
• Estimated Study Completion Date: January 2025
• Estimated Primary Completion Date: September 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Hong Kong, Korea, Republic of, Taiwan, Thailand, United States

Administrative Information

• NCT Number: NCT03674567
• Other Study ID Numbers: FLX475-02; KEYNOTE-877 ( Other Identifier: Merck Sharp & Dohme LLC ); MK-3475-877 ( Other Identifier: Merck Sharp & Dohme LLC )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: RAPT Therapeutics, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: RAPT Therapeutics, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Merck Sharp & Dohme LLC

Investigators

• Study Director: William Ho, MD, PhD; RAPT Therapeutics, Inc.

• PRS Account: RAPT Therapeutics, Inc.
• Verification Date: April 2024