Clinical Trials /

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

NCT02880371

Description:

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).

Related Conditions:
  • Bladder Carcinoma
  • Breast Carcinoma
  • Colorectal Carcinoma
  • Gastric Carcinoma
  • Head and Neck Squamous Cell Carcinoma
  • Melanoma
  • Non-Small Cell Lung Carcinoma
  • Ovarian Carcinoma
  • Pancreatic Ductal Adenocarcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title:A Study of ARRY-382 in Combination With Pembrolizumab for the Treatment of Patients With Advanced Solid Tumors
  • Official Title:A 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

Clinical Trial IDs

  • ORG STUDY ID: ARRAY-382-201
  • NCT ID: NCT02880371

Trial Conditions

  • Advanced Solid Tumors

Trial Interventions

DrugSynonymsArms
ARRY-382Part A
PembrolizumabPart A

Trial Purpose

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), to assess the pharmacodynamic effects of the combination and to describe the preliminary antitumor activity of the combination in patients with advanced unresectable/metastatic melanoma (Part B), and to estimate the efficacy of the combination in patients with PD-L1-positive NSCLC (Part C).

Detailed Description

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

Each part of the study consists of a 28-day screening period, 21-day treatment cycles until disease progression, unacceptable toxicity, withdrawal of consent, or death (or other discontinuation criteria are met), and a 30-day safety follow-up period. Patients will be monitored for overall survival (OS) until 1 year after the date of the last patient's first visit.

Trial Arms

NameTypeDescriptionInterventions
Part AExperimentalPatients in Part A will receive escalating doses of single-agent ARRY-382 in combination with 2 mg/kg pembrolizumab.
  • ARRY-382
  • Pembrolizumab
Part BExperimentalPatients in Part B will receive the RP2D dose of ARRY-382 determined during Part A in combination with 2 mg/kg pembrolizumab.
  • ARRY-382
  • Pembrolizumab
Part CExperimentalPatients in Part C will receive the RP2D dose of ARRY-382 determined during Part A in combination with 2 mg/kg pembrolizumab.
  • ARRY-382
  • Pembrolizumab

Eligibility Criteria

Key Inclusion Criteria:

All Study Parts:

- Personally signed and dated informed consent form

- Male or female ≥ 18 years of age

- Diagnosis of cancer that has been histologically or cytologically confirmed

- Eastern Cooperative Oncology Group Performance Status of 0 or 1

- For male patients and female patients of childbearing potential, agreement to use an effective method of contraception per institutional standards through 4 months after the last administration of study treatment (i.e., ARRY-382, pembrolizumab)

- For females of childbearing potential only, negative serum human chorionic gonadotropin (hCG) pregnancy test result at baseline and nonlactating

- Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures

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, with progression following treatment with a platinum-containing chemotherapy regimen or with progression following locally approved appropriate therapy for patients with EGFR or anaplastic lymphoma kinase (ALK) genomic tumor aberrations and measurable or evaluable, nonmeasurable disease as defined by RECIST v1.1

Part B:

- Advanced, unresectable, or metastatic melanoma with or without prior treatment, measurable disease as defined by RECIST v1.1, and a minimum of 3 lesions

Part C:

- Advanced/metastatic PD-L1-positive NSCLC, with progression following treatment with a platinum-containing chemotherapy regimen, or with progression following locally approved appropriate therapy for patients with EGFR or ALK genomic tumor aberrations and measurable disease as defined by RECIST v1.1

Key Exclusion Criteria:

- Prior treatment as follows:

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

- Parts B and C: an immune CPI (e.g., PD-1, PD-L1, or CTLA-4 inhibitor) or a CSF-1R or CSF-1 (or MCSF) 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

Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Both
Healthy Volunteers:No

Primary Outcome Measures

Measure:(Phase 1b/Part A) Incidence of dose-limiting toxicities (DLTs)
Time Frame:Cycle 1 (up to 21 days)
Safety Issue:No
Description:

Secondary Outcome Measures

Measure:(Phase 1b/Part A, Part B) Preliminary antitumor activity of the combination in terms of objective response rate
Time Frame:Phase 1b is expected to last until disease progression; Duration of Part B is approximately 2.5 years
Safety Issue:No
Description:
Measure:(Phase 1b/Part A, Part B, Part C) Preliminary antitumor activity of the combination based on immune-related response criteria
Time Frame:Phase 1b is expected to last until disease progression; Duration of Part B is approximately 2.5 years; Duration of Part C is approximately 1 year
Safety Issue:No
Description:
Measure:(Phase 1b/Part A, Part B, Part C) Safety and tolerability of the combination in terms of adverse events and serious adverse events
Time Frame:Phase 1b: Patient safety will be evaluated throughout the treatment period, which is expected to last 6-10 months for each patient; Duration of Part B is approximately 2.5 years; Duration of Part C is approximately 1 year
Safety Issue:No
Description:
Measure:(Part B) Evaluation of the pharmacodynamics of single-agent ARRY-382 in tumor tissue after 14 days of treatment in terms of immune biomarkers by IHC and/or RNA analysis
Time Frame:Approximately 14 days
Safety Issue:No
Description:
Measure:(Phase 1b/Part A, Part B, Part C) Preliminary antitumor activity of the combination in terms of duration of response
Time Frame:Phase 1b is expected to last until disease progression; Duration of Part B is approximately 2.5 years; Duration of Part C is approximately 1 year
Safety Issue:No
Description:
Measure:(Phase 1b/Part A, Part B, Part C) Preliminary antitumor activity of the combination in terms of progression-free survival
Time Frame:Phase 1b is expected to last until disease progression; Duration of Part B is approximately 2.5 years; Duration of Part C is approximately 1 year
Safety Issue:No
Description:
Measure:(Phase 1b/Part A, Part B, Part C) Preliminary antitumor activity of the combination in terms of overall survival
Time Frame:Duration of Phase 1b is approximately 1 year; Duration of Part B is approximately 2.5 years; Duration of Part C is approximately 1 year
Safety Issue:No
Description:
Measure:(Phase 1b/Part A, Part B, Part C) Evaluation of the plasma concentration-time profiles of ARRY-382 and its metabolites in the combination
Time Frame:Phase 1b: Patient safety will be evaluated throughout the treatment period, which is expected to last 6-10 months for each patient; Duration of Part B is approximately 2.5 years; Duration of Part C is approximately 1 year
Safety Issue:No
Description:
Measure:(Phase 1b/Part A, Part B, Part C) Area under the plasma concentration-time curve over the dosing interval (AUCτ) of ARRY-382 and its three metabolites
Time Frame:Phase 1b: Patient safety will be evaluated throughout the treatment period, which is expected to last 6-10 months for each patient; Duration of Part B is approximately 2.5 years; Duration of Part C is approximately 1 year
Safety Issue:No
Description:
Measure:(Phase 1b/Part A, Part B, Part C) Maximum plasma concentration (Cmax) of ARRY-382 and its three metabolites
Time Frame:Phase 1b: Patient safety will be evaluated throughout the treatment period, which is expected to last 6-10 months for each patient; Duration of Part B is approximately 2.5 years; Duration of Part C is approximately 1 year
Safety Issue:No
Description:
Measure:(Phase 1b/Part A, Part B, Part C) Time of maximum observed plasma concentration (Tmax) of ARRY-382 and its three metabolites
Time Frame:Phase 1b: Patient safety will be evaluated throughout the treatment period, which is expected to last 6-10 months for each patient; Duration of Part B is approximately 2.5 years; Duration of Part C is approximately 1 year
Safety Issue:No
Description:
Measure:(Phase 1b/Part A, Part B, Part C) Plasma concentration measured just before the next dose of study drug (Ctrough) of ARRY-382 and its three metabolites
Time Frame:Phase 1b: Patient safety will be evaluated throughout the treatment period, which is expected to last 6-10 months for each patient; Duration of Part B is approximately 2.5 years; Duration of Part C is approximately 1 year
Safety Issue:No
Description:
Measure:(Phase 1b/Part A, Part B, Part C) Accumulation ratio based on AUC (RAUC) of ARRY-382 and its three metabolites
Time Frame:Phase 1b: Patient safety will be evaluated throughout the treatment period, which is expected to last 6-10 months for each patient; Duration of Part B is approximately 2.5 years; Duration of Part C is approximately 1 year
Safety Issue:No
Description:
Measure:(Phase 1b/Part A, Part B, Part C) Metabolite-to-parent ratio based on AUC (MRAUC) of ARRY-382 and its three metabolites
Time Frame:Phase 1b: Patient safety will be evaluated throughout the treatment period, which is expected to last 6-10 months for each patient; Duration of Part B is approximately 2.5 years; Duration of Part C is approximately 1 year
Safety Issue:No
Description:
Measure:(Phase 1b/Part A, Part B, Part C) Metabolite-to-parent ratio based on Cmax (MRCmax) of ARRY-382 and its three metabolites
Time Frame:Phase 1b: Patient safety will be evaluated throughout the treatment period, which is expected to last 6-10 months for each patient; Duration of Part B is approximately 2.5 years; Duration of Part C is approximately 1 year
Safety Issue:No
Description:
Measure:(Phase 1b/Part A, Part B, Part C) Accumulation ratio based on Cmax (RCmax) of ARRY-382 and its three metabolites
Time Frame:Phase 1b: Patient safety will be evaluated throughout the treatment period, which is expected to last 6-10 months for each patient; Duration of Part B is approximately 2.5 years; Duration of Part C is approximately 1 year
Safety Issue:No
Description:

Trial Keywords

  • Advanced Solid Tumors
  • Pembrolizumab
  • ARRY-382