Clinical trial NCT02880371: A Study of ARRY-382 in Combination With Pembrolizumab for the Treatment of Patients With Advanced Solid Tumors
Official title: A Phase 1b/2 Study of ARRY-382 in Combination With Pembrolizumab, a Programmed Cell Death Receptor 1 (PD-1) Antibody, for the Treatment of Patients With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Advanced Solid Tumors
Keywords: Advanced Solid Tumors
Pembrolizumab
ARRY-382
CSF-1R
CSF1R
cfms
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2016-08-26
Enrollment: 82
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is an open-label, multicenter Phase 1b/2 study to determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of ARRY-382 in combination with pembrolizumab in adult patients with selected advanced solid tumors (Part A/Phase 1b); and to estimate the efficacy of the combination in three separate cohorts: 1) patients with advanced solid tumors that have progressed on prior PD-1/PD-L1inhibitors, 2) patients with platinum-resistant ovarian cancer and 3) patients with pancreatic ductal adenocarcinoma (Phase 2).

Detailed description: ARRY-382 is an inhibitor of CSF1R (colony-stimulating factor-1 receptor).

Each phase of the study consists of a 28-day screening period; 21-day treatment cycles with the combination of ARRY-382 and pembrolizumab until disease progression as determined by the Investigator, unacceptable toxicity, withdrawal of consent, or death (or other discontinuation criteria are met), and a 30-day safety follow-up period. Patients in all cohorts/phases will be monitored for overall survival (OS) until 1 year after the date of the last patient's first visit.

Eligibility criteria: Key Inclusion Criteria

All Study Parts:

* Diagnosis of cancer that has been histologically or cytologically confirmed
* Eastern Cooperative Oncology Group Performance Status of 0 or 1

Part A (1 of the following):

* Ovarian cancer, triple-negative breast cancer, head and neck squamous cell cancer, bladder cancer, metastatic colorectal cancer, pancreatic ductal adenocarcinoma, or gastric cancer that is measurable or evaluable, nonmeasurable as defined by RECIST v1.1 and meets 1 of the following criteria:

  * is refractory to standard of care
  * no standard therapy available
  * patient refuses standard therapy
* Advanced, unresectable, or metastatic melanoma with or without prior treatment and measurable or evaluable, nonmeasurable disease as defined by RECIST v1.1
* Advanced/metastatic PD-L1-positive NSCLC (defined as a tumor proportion score \[TPS\] ≥ 50%) with measurable or evaluable, non-measurable disease as defined by RECIST v1.1 (1 of the following):

  * 1) No prior systemic chemotherapy if tumor does not have EGFR or ALK genomic aberrations
  * 2) Disease progression on or after platinum-containing chemotherapy;
  * 3) If tumor has EGFR or ALK genomic aberrations, disease progression on an FDA-approved therapy for EGFR or ALK genomic tumor aberrations

Phase 2 (1 of the following):

* Advanced/metastatic solid tumor with PD as defined by RECIST 1.1 or irRC on an anti-PD-1- or anti-PD-L1-containing regimen as their most recent prior therapy
* Advanced/metastatic epithelial ovarian cancer, peritoneal cancer or tubal cancer with measurable disease as defined by RECIST 1.1, that had progressed within 6 months of completing ≥ 4 cycles of platinum-based therapy
* Advanced/metastatic PDA that is locally advanced, unresectable or metastatic with measurable disease as defined by RECIST v1.1 in patients who have received at least one prior line of systemic therapy for their disease

Key Exclusion Criteria

1. Prior treatment as follows:

   * Part A: an immune CPI (e.g., PD-1, PD-L1, or cytotoxic T-lymphocyte antigen 4 \[CTLA-4\] inhibitor).

   NOTE: For patients with melanoma, prior treatment with ipilimumab is allowed if it was administered as adjuvant therapy and treatment was completed at least 3 months prior to enrollment.
   * Phase 2:

     * A CSF-1R inhibitor or CSF-1 (or MCSF) inhibitor.
     * prOVCA and PDA patients only: an immune CPI (e.g., PD-1, PD-L1, or CTLA-4 inhibitor)
2. Symptomatic brain metastasis at screening
3. Active autoimmune disease, documented history of autoimmune syndrome or disease, or a chronic medical condition that requires chronic steroid therapy or immunosuppressive medication
4. History of pneumonitis or interstitial lung disease
5. Severe, acute, or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration or that may interfere with the interpretation of study results and, in the judgment of the Investigator, would make the patient an inappropriate candidate for the study
6. Ocular melanoma

Primary outcomes:
measure: Phase 1b, Part A: Number of Participants With Dose-Limiting Toxicities (DLT)
timeFrame: Cycle 1 (up to 21 days)
measure: Phase 2 Cohorts: Objective Response Rate (ORR)
timeFrame: From day of first dose to 30 days after last dose (maximum up to 13.5 months)
Secondary outcomes:
measure: Phase 1b, Part A: Objective Response Rate (ORR)
timeFrame: From day of first dose to 30 days after last dose (maximum up to 34.7 months)
measure: Phase 1b, Part A and Phase 2 Cohorts: Duration of Response (DOR)
timeFrame: From date of first documented CR or PR up to disease progression or death (for Phase 1b: maximum up to 34.7 months, for Phase 2: maximum up to 13.5 months)
measure: Phase 1b, Part A and Phase 2 Cohorts: Progression-Free Survival (PFS)
timeFrame: From day of first dose until disease progression or death due to any cause or till last tumor assessment date (for Phase 1b: maximum up to 34.7 months, for Phase 2: maximum up to 13.5 months)
measure: Phase 1b, Part A and Phase 2 Cohorts: Overall Survival (OS)
timeFrame: From day of first dose till death due to any cause or date of last contact (for Phase 1b: maximum up to 34.7 months, for Phase 2: maximum up to 13.5 months)
measure: Phase 1b, Part A and Phase 2 Cohorts: Percentage of Participants With Immune-Related Response Rate (irRR)
timeFrame: From day of first dose till up to end of study treatment (for Phase 1b: maximum up to 33.7 months, for Phase 2: maximum up to 12.5 months)
measure: Phase 1b, Part A and Phase 2 Cohorts: Immune-Related Progression-Free Survival (irPFS)
timeFrame: From the start of treatment to the time of first documented progression, or death (for Phase 1b: maximum up to 34.7 months, for Phase 2: maximum up to 13.5 months)
measure: Phase 2 prOVCA: Change From Baseline in Tumor Markers at Day 1 of Cycle 1, 2, 3, 4, 5, 6, 7, Day 8, 15 of Cycle 1 and Treatment Discontinuation
timeFrame: Baseline, Day 1 of Cycle 1, 2, 3, 4, 5, 6, 7, Day 8, 15 of Cycle 1 and Treatment discontinuation (before 13.5 months)
measure: Phase 1b, Part A and Phase 2 Cohorts: Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: First dose of study drug up to 30 days after last dose (for Phase 1b: maximum up to 34.7 months, for Phase 2: maximum up to 13.5 months)
measure: Phase 1b, Part A and Phase 2 Cohorts: Number of Participants With Newly Occurring or Worsening Serum Chemistry Laboratory Abnormalities Graded by Common Terminology Criteria for Adverse Events (CTCAE) Grade 4.03
timeFrame: First dose of study drug up to 30 days after last dose (for Phase 1b: maximum up to 34.7 months, for Phase 2: maximum up to 13.5 months)
measure: Phase 1b, Part A and Phase 2 Cohorts: Number of Participants With Newly Occurring or Worsening Hematology and Coagulation Laboratory Abnormalities Graded by CTCAE Grade 4.03
timeFrame: First dose of study drug up to 30 days after last dose (for Phase 1b: maximum up to 34.7 months, for Phase 2: maximum up to 13.5 months)
measure: Phase 1b, Part A and Phase 2 Cohorts: Number of Participants With Newly Occurring Abnormal Liver Function Tests
timeFrame: First dose of study drug up to 30 days after last dose (for Phase 1b: maximum up to 34.7 months, for Phase 2: maximum up to 13.5 months)
measure: Phase 1b, Part A and Phase 2 Cohorts: Number of Participants With Shift in Thyroid Panel Severity From Baseline Grade to Post Baseline Grades
timeFrame: Baseline, 30 days after last dose (for Phase 1b: maximum up to 34.7 months, for Phase 2: maximum up to 13.5 months)
measure: Phase 1b, Part A and Phase 2 Cohorts: Number of Participants With Clinically Significant Urinalysis Finding
timeFrame: First dose of study drug up to 30 days after last dose (for Phase 1b: maximum up to 34.7 months, for Phase 2: maximum up to 13.5 months)
measure: Phase 1b, Part A and Phase 2 Cohorts: Number of Participants With Newly Occurring Clinically Notable Vital Sign Abnormalities
timeFrame: First dose of study drug up to 30 days after last dose (for Phase 1b: maximum up to 34.7 months, for Phase 2: maximum up to 13.5 months)
measure: Phase 1b, Part A and Phase 2 Cohorts: Plasma Concentration Versus Time Profile of ARRY-382
timeFrame: Pre dose of ARRY-382 (120 minutes prior to administration): on Day 15 of Cycle 1, on Day 1 of Cycle 2, 3, 4, 5, 6, 7, 8, 9 , 10; 1 hour(hr) (±5 min), 2 hours(hrs) (±10 min), 4 hrs (±20 min) and 8 hrs (±30 min) post dose of ARRY-382 on Day 1 of Cycle 1, 2
measure: Phase 1b, Part A and Phase 2 Cohorts: Plasma Concentration Versus Time Profile of Metabolite AR00469099
timeFrame: Pre dose of ARRY-382 (120 minutes prior to administration): on Day 15 of Cycle 1, on Day 1 of Cycle 2, 3, 4, 5, 6, 7, 8, 9 , 10; 1 hr (±5 min), 2 hrs (±10 min), 4 hrs (±20 min), and 8 hrs (±30 min) post dose of ARRY-382 on Day 1 of Cycle 1, 2
measure: Phase 1b, Part A and Phase 2 Cohorts: Plasma Concentration Versus Time Profile of Metabolite AR00469100
timeFrame: Pre dose of ARRY-382 (120 minutes prior to administration): on Day 15 of Cycle 1, on Day 1 of Cycle 2, 3, 4, 5, 6, 7, 8, 9 , 10; 1 hr (±5 min), 2 hrs (±10 min), 4 hrs (±20 min), and 8 hrs (±30 min) post dose of ARRY-382 on Day 1 of Cycle 1, 2
measure: Phase 1b, Part A and Phase 2 Cohorts: Plasma Concentration Versus Time Profile of Metabolite AR00470870
timeFrame: Pre dose of ARRY-382 (120 minutes prior to administration): on Day 15 of Cycle 1, on Day 1 of Cycle 2, 3, 4, 5, 6, 7, 8, 9 , 10; 1 hr (±5 min), 2 hrs (±10 min), 4 hrs (±20 min), and 8 hrs (±30 min) post dose of ARRY-382 on Day 1 of Cycle 1, 2
measure: Phase 1b, Part A and Phase 2 Cohorts: Area Under the Plasma Concentration-Time Curve Over a Dosing Interval at Steady-State (AUCtau, ss) for ARRY-382 and Metabolites (AR00469099, AR00469100, and AR00470870)
timeFrame: 0 to 24 hrs after administration of ARRY-382 on Day 1 of Cycle 2
measure: Phase 1b, Part A and Phase 2 Cohorts: Maximum Observed Plasma Concentration (Cmax) for ARRY-382 and Metabolites (AR00469099, AR00469100, and AR00470870)
timeFrame: Pre dose of ARRY-382 (120 minutes prior to administration), 1 hr (±5 min), 2 hrs (±10 min), 4 hrs (±20 min), and 8 hrs (±30 min) after administration of ARRY-382 on Day 1 of Cycle 1 and 2
measure: Phase 1b, Part A and Phase 2 Cohorts: Ctrough at Steady State for ARRY-382 and Metabolites (AR00469099, AR00469100, and AR00470870)
timeFrame: Pre dose of ARRY-382 (120 minutes prior to administration) on Day 1 of Cycle 2
measure: Phase 1b, Part A and Phase 2 Cohorts: Time to Reach Maximum Observed Plasma Concentration (Tmax) for ARRY-382 and Metabolites (AR00469099, AR00469100, and AR00470870)
timeFrame: Pre dose of ARRY-382 (120 minutes prior to administration), 1 hr (±5 min), 2 hrs (±10 min), 4 hrs (±20 min), and 8 hrs (±30 min) after administration of ARRY-382 on Day 1 of Cycle 1 and 2
measure: Phase 1b, Part A and Phase 2 Cohorts: Metabolite-to-Parent Ratio (MR) for ARRY-382 and Metabolites (AR00469099, AR00469100, and AR00470870)
timeFrame: Pre dose of ARRY-382 (120 minutes prior to administration),1 hrs (±5 min), 2 hrs (±10 min), 4 hrs (±20 min), and 8 hrs (±30 min) after administration of ARRY-382 on Day 1 of Cycle 1 and 2
measure: Phase 1b, Part A and Phase 2 Cohorts: Accumulation Ratio (R) for ARRY-382 and Metabolites (AR00469099, AR00469100, and AR00470870)
timeFrame: Pre dose of ARRY-382 (120 minutes prior to administration),1 hr (±5 min), 2 hrs (±10 min), 4 hrs (±20 min), and 8 hrs (±30 min) after administration of ARRY-382 on Day 1 of Cycle 1 and 2
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Ronald Reagan UCLA Medical Center
state: California
city: Los Angeles
country: United States
facility: UCLA Hematology/Oncology
state: California
city: Santa Monica
country: United States
facility: UCLA Hematology/Oncology - Santa Monica
state: California
city: Aurora
country: United States
facility: University of Colorado Denver
state: Colorado
city: Aurora
country: United States
facility: University of Colorado Hospital
state: Colorado
city: Port Saint Lucie
country: United States
facility: Hem-Onc Associates of Treasure Coast
state: Florida
city: Fort Wayne
country: United States
facility: Parkview Cancer Institute
state: Indiana
city: Fort Wayne
country: United States
facility: Parkview Regional Medical Center
state: Indiana
city: Fort Wayne
country: United States
facility: Parkview Research Center
state: Indiana
city: Fort Wayne
country: United States
facility: PPG
state: Indiana
city: Lafayette
country: United States
facility: Horizon Oncology Research, Inc.
state: Indiana
city: Cedar Rapids
country: United States
facility: Hall-Perrine Cancer Center Laboratory
state: Iowa
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Detroit
country: United States
facility: Karmanos Cancer Institute
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic Labs - Rochester Superior
state: Minnesota
city: Saint Paul
country: United States
facility: Regions Cancer Care Center
state: Minnesota
city: Saint Paul
country: United States
facility: Regions Hospital Pharmacy
state: Minnesota
city: Saint Paul
country: United States
facility: Regions Hospital
state: Minnesota
city: Saint Paul
country: United States
facility: HealthPartners Neurosciences Center
state: Minnesota
city: Nashville
country: United States
facility: Tennessee Oncology PLLC
state: Tennessee
city: Nashville
country: United States
facility: Tennessee Oncology, PLLC
state: Tennessee
city: Nashville
country: United States
facility: The Sarah Cannon Research Institute
state: Tennessee
city: San Antonio
country: United States
facility: UT Health Cancer Center
state: Texas
city: Salt Lake City
country: United States
facility: UTAH Cancer Specialists
state: Utah
city: Salt Lake City
country: United States
facility: ARUP Laboratories, Inc.
state: Utah
city: Charlottesville
country: United States
facility: University of Virginia Cancer Center
state: Virginia
city: Charlottesville
country: United States
facility: UVA Health System
state: Virginia
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
citation: Johnson M, Dudek AZ, Sukari A, Call J, Kunk PR, Lewis K, Gainor JF, Sarantopoulos J, Lee P, Golden A, Harney A, Rothenberg SM, Zhang Y, Goldman JW. ARRY-382 in Combination with Pembrolizumab in Patients with Advanced Solid Tumors: Results from a Phase 1b/2 Study. Clin Cancer Res. 2022 Jun 13;28(12):2517-2526. doi: 10.1158/1078-0432.CCR-21-3009.