Clinical trial NCT03674567: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Advanced Cancer
Keywords: Non-small Cell Lung Cancer
Head and Neck Squamous Cell Carcinoma
Breast Cancer
Urothelial Carcinoma
Nasopharyngeal Carcinoma
Cervical Cancer
Lymphoma
Lead sponsor: RAPT Therapeutics, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2018-09-17
Enrollment: 323
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: 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
timeFrame: Approximately 18 weeks
measure: Overall response rate in subjects treated with FLX475 as a single agent and in combination with pembrolizumab
timeFrame: Through study completion (approximately 2 years)
Secondary outcomes:
Other outcomes:
Locations:
city: Gilbert
country: United States
facility: Banner MD Anderson Cancer Center
state: Arizona
city: Duarte
country: United States
facility: City of Hope
state: California
city: Los Angeles
country: United States
facility: University of California, Los Angeles JCCC Clinical Research Unit
state: California
city: New Haven
country: United States
facility: Yale Cancer Center
state: Connecticut
city: Washington
country: United States
facility: Georgetown - Lombardi Comprehensive Cancer Center
state: District of Columbia
city: Saint Petersburg
country: United States
facility: Comprehensive Hematology and Oncology, LLC
state: Florida
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Atlanta
country: United States
facility: Emory Winship Cancer Institute
state: Georgia
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Louisville
country: United States
facility: University of Louisville Hospital/James Graham Brown Cancer Center
state: Kentucky
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Santa Fe
country: United States
facility: Quantum Santa Fe
state: New Mexico
city: New York
country: United States
facility: New York Presbyterian Hospital-Columbia University Medical Center
state: New York
city: Huntersville
country: United States
facility: Carolina BioOncology Institute
state: North Carolina
city: Dallas
country: United States
facility: Mary Crowley Cancer Research Center
state: Texas
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
city: Seattle
country: United States
facility: University of Washington
state: Washington
city: Heidelberg
country: Australia
facility: Austin Hospital
state: Victoria
city: Nedlands
country: Australia
facility: Linear Clinical Research Limited
state: Western Australia
city: High West
country: Hong Kong
facility: Queen Mary Hospital - Lymphoma
city: High West
country: Hong Kong
facility: Queen Mary Hospital
city: Shatin
country: Hong Kong
facility: Prince of Wales Hospital
city: Chungbuk
country: Korea, Republic of
facility: Chungbuk National University Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital
city: Tainan
country: Taiwan
facility: Chi Mei Meidcal Center
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital
city: Bangkok
country: Thailand
facility: King Chulaongkorn Memorial Hospital
city: Bangkok
country: Thailand
facility: Ramathibodi Hospital
Study officials:
affiliation: RAPT Therapeutics, Inc.
name: William Ho, MD, PhD
role: STUDY_DIRECTOR
References: