A Study of ARRY-382 in Combination With Pembrolizumab for the Treatment of Patients With Advanced Solid Tumors

NCT02880371 | Terminated Phase 1 Results FDA Drug

• 2 other identifiers: ARRAY-382-201C4261001
• Study Type: interventional
• Target: 82
• Locations: 1 country
• Sites: 30

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).

Conditions

Advanced Solid Tumors

Keywords

Advanced Solid Tumors; Pembrolizumab; ARRY-382; CSF-1R; CSF1R; cfms

Outcome Measures

Primary Outcomes (2)

• Phase 1b, Part A: Number of Participants With Dose-Limiting Toxicities (DLT)

  DLT: adverse event (AE) or abnormal laboratory value not clearly attributable to an extraneous cause, such as disease progression, intercurrent illness, or concomitant medications occurring during 21 days of Cycle 1, met 1 of the criteria A) nonhematologic AEs: recurring grade 2 pneumonitis, grade 3 events (irAE, QTcF prolongation, rash; other grade 3/4 except alopecia, nausea, diarrhea, vomiting, tumor flare, pseudoprogression, endocrinopathy); B) hematology AEs/laboratory abnormalities: grade 4 events except lymphopenia, neutropenia, electrolyte imbalances or abnormalities, grade 3 thrombocytopenia, febrile neutropenia, grade 4 AST/ALT elevation, grade 3 AST/ALT elevation lasting \>7 days, associated with bilirubin levels\>=2\*ULN or international normalized ratio \>1.5, grade 3 bilirubin elevation \>=3, CK elevation \>=grade 3 lasting, increase in creatinine \>=1.5\*baseline value, dose delay (dose interruption for \>14 days) or other (inability to receive at least 67% of ARRY-382 doses).

  Cycle 1 (up to 21 days)

• Phase 2 Cohorts: Objective Response Rate (ORR)

  ORR was defined as the percentage of participants who achieved a best overall response (BOR) of complete response (CR) or partial response (PR) as determined by investigator review of radiographic disease assessments per Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1. As per RECIST v1.1: CR = disappearance of target and non-target lesions and normalization of tumor markers. Pathological lymph nodes must have short axis measures less than (\<) 10 millimeter (mm). PR = at least a 30% decrease in the sum of measures (longest diameter for tumor lesions and short axis measure for nodes) of target lesions, taking as reference the baseline sum of diameters. Non-target lesions must be non-progressive disease (PD). The analysis was based on confirmed responses for which CR or PR must be confirmed by repeat disease assessment studies performed no less than 4 weeks after the criteria for response were first met to qualify as CR or PR, respectively.

  From day of first dose to 30 days after last dose (maximum up to 13.5 months)

Secondary Outcomes (24)

• Phase 1b, Part A: Objective Response Rate (ORR)

  From day of first dose to 30 days after last dose (maximum up to 34.7 months)

• Phase 1b, Part A and Phase 2 Cohorts: Duration of Response (DOR)

  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)

• Phase 1b, Part A and Phase 2 Cohorts: Progression-Free Survival (PFS)

  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)

• Phase 1b, Part A and Phase 2 Cohorts: Overall Survival (OS)

  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)

• Phase 1b, Part A and Phase 2 Cohorts: Percentage of Participants With Immune-Related Response Rate (irRR)

  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)

Study Arms (2)

Phase 1b/Part A

EXPERIMENTAL

Patients in Part A will receive escalating doses of single-agent ARRY-382 in combination with 2 mg/kg pembrolizumab.

Drug: ARRY-382; Drug: Pembrolizumab

Phase 2

EXPERIMENTAL

Patients in Phase 2 will receive the MTD/RP2D dose of ARRY-382 determined during Part A in combination with 200mg pembrolizumab.

Drug: ARRY-382; Drug: Pembrolizumab

Interventions

ARRY-382 DRUG

ARRAY-382 will be taken by mouth once daily at a fixed dose.

Phase 1b/Part A; Phase 2

Pembrolizumab DRUG

Pembrolizumab will be administered intravenously over 30 minutes every 3 weeks.

Phase 1b/Part A; Phase 2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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):
• \) No prior systemic chemotherapy if tumor does not have EGFR or ALK genomic aberrations
• \) Disease progression on or after platinum-containing chemotherapy;
• \) 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

You may not qualify if:

• 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)
• Symptomatic brain metastasis at screening
• Active autoimmune disease, documented history of autoimmune syndrome or disease, or a chronic medical condition that requires chronic steroid therapy or immunosuppressive medication
• History of pneumonitis or interstitial lung disease
• 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
• Ocular melanoma

Sponsors & Collaborators

• Pfizer: lead

Study Sites (30)

Ronald Reagan UCLA Medical Center

Los Angeles, California, 90095, United States

Location

UCLA Hematology/Oncology

Los Angeles, California, 90095, United States

Location

UCLA Hematology/Oncology - Santa Monica

Santa Monica, California, 90404, United States

Location

University of Colorado Denver

Aurora, Colorado, 80045, United States

Location

University of Colorado Hospital

Aurora, Colorado, 80045, United States

Location

Hem-Onc Associates of Treasure Coast

Port Saint Lucie, Florida, 34952, United States

Location

Parkview Cancer Institute

Fort Wayne, Indiana, 46845, United States

Location

Parkview Regional Medical Center

Fort Wayne, Indiana, 46845, United States

Location

Parkview Research Center

Fort Wayne, Indiana, 46845, United States

Location

PPG

Fort Wayne, Indiana, 46845, United States

Location

Horizon Oncology Research, Inc.

Lafayette, Indiana, 47905, United States

Location

Hall-Perrine Cancer Center Laboratory

Cedar Rapids, Iowa, 52403, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Mayo Clinic Labs - Rochester Superior

Rochester, Minnesota, 55901, United States

Location

Regions Cancer Care Center

Saint Paul, Minnesota, 55101, United States

Location

Regions Hospital Pharmacy

Saint Paul, Minnesota, 55101, United States

Location

Regions Hospital

Saint Paul, Minnesota, 55101, United States

Location

HealthPartners Neurosciences Center

Saint Paul, Minnesota, 55130, United States

Location

Tennessee Oncology PLLC

Nashville, Tennessee, 37203, United States

Location

Tennessee Oncology, PLLC

Nashville, Tennessee, 37203, United States

Location

The Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

Location

UT Health Cancer Center

San Antonio, Texas, 78229, United States

Location

UTAH Cancer Specialists

Salt Lake City, Utah, 84106, United States

Location

ARUP Laboratories, Inc.

Salt Lake City, Utah, 84108-1221, United States

Location

University of Virginia Cancer Center

Charlottesville, Virginia, 22903, United States

Location

UVA Health System

Charlottesville, Virginia, 22908, United States

Location

Related Publications (1)

• 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.

  PMID: 35302585 DERIVED

Related Links

• To obtain contact information for a study center near you, click here.

MeSH Terms

Interventions

pembrolizumab

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer Inc.

ClinicalTrials.gov_Inquiries@pfizer.com

1-800-718-1021

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 2, 2016
• First Posted: August 26, 2016
• Study Start: September 1, 2016
• Primary Completion: September 17, 2019
• Study Completion: October 24, 2019
• Last Updated: June 16, 2022
• Results First Posted: June 16, 2022

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will share

Locations

US (30)