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

RAPT Therapeutics

Status and phase: Active, not recruiting; Phase 2; Phase 1

Conditions: Advanced Cancer

Treatments: Drug: pembrolizumab (KEYTRUDA®); Drug: FLX475

Study type: Interventional

Funder types: Industry

Identifiers

NCT03674567

MK-3475-877 (Other Identifier)

KEYNOTE-877 (Other Identifier)

FLX475-02

Details and patient eligibility

About

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.

Enrollment: 323 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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323 participants in 4 patient groups

Part 1a: Monotherapy Dose Escalation

Experimental group

Description:

Eligible subjects will be enrolled in sequential cohorts treated with successively higher doses of FLX475 as monotherapy.

Treatment:

Drug: FLX475

Part 1b: Combination Dose Escalation

Experimental group

Description:

Eligible subjects will be enrolled in sequential cohorts treated with successively higher doses of FLX475 in combination with pembrolizumab.

Treatment:

Drug: FLX475

Drug: pembrolizumab (KEYTRUDA®)

Part 2a: Monotherapy Expansion Cohorts

Experimental group

Description:

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.

Treatment:

Drug: FLX475

Part 2b: Combination Expansion Cohorts

Experimental group

Description:

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.

Treatment:

Drug: FLX475

Drug: pembrolizumab (KEYTRUDA®)