A Combination Clinical Study of PLX3397 and Pembrolizumab To Treat Advanced Melanoma and Other Solid Tumors

NCT02452424 | Terminated Phase 1 Results FDA Drug

• 2 other identifiers: PLX108-14KEYNOTE-103
• Study Type: interventional
• Target: 78
• Locations: 1 country
• Sites: 12

Brief Summary

The goal of this clinical research study is to learn how PLX3397 and pembrolizumab work together to affect cancer cells. PLX3397 is designed to target the receptor for CSF1 (CSF1R). Pembrolizumab is designed to block the interaction between the receptor PD-1 and molecules that bind PD-1. In this study, PLX3397 and pembrolizumab are being given together in order to study their combined effects on patients' immune responses to their tumors. Tumor-specific immune responses have been shown to kill cancer cells and/or to stop tumors from growing. Part 1 of the study (dose-escalation phase) will establish the safest dose of PLX3397 to be given in combination with pembrolizumab. Part 2 of the study (expansion phase) will include an evaluation of efficacy of this combination in the following tumor types:

• Advanced melanoma: prior anti-PD-1/PD-L1 therapy but never responded
• Advanced melanoma: prior anti-PD-1/PD-L1 therapy and responded but later progressed as defined by irRECIST while on therapy
• Non-small cell lung cancer
• Ovarian cancer
• Gastrointestinal Stromal Tumor (GIST)
• Squamous cell cancer of the head and neck

Conditions

Melanoma; Non-small Cell Lung Cancer; Squamous Cell Carcinoma of the Head and Neck; Gastrointestinal Stromal Tumor (GIST); Ovarian Cancer

Outcome Measures

Primary Outcomes (1)

• Treatment-emergent Adverse Events (TEAEs) in Participants Regardless of Causality While Taking PLX3397 in Combination With Pembrolizumab

  Treatment-emergent Adverse Events (TEAEs) in participants regardless of causality while taking PLX3397 in combination with pembrolizumab are reported

  1 year (Dose Escalation); 2 years (Dose Expansion)

Secondary Outcomes (1)

• Summary of the Percentage of Participants With Objective Response Rate Assessed by RECIST v1.1 During Pembrolizumab and PLX3397

  1 year (Dose Escalation); 2 years (Dose Expansion)

Study Arms (2)

PLX3397 and Pembrolizumab (Part 1)

EXPERIMENTAL

Open-label, sequential PLX3397 dose escalation with a fixed dose of pembrolizumab in approximately 24 patients with advanced solid tumors. (Enrollment complete- 33 enrolled)

Drug: PLX3397; Biological: Pembrolizumab

PLX3397 and Pembrolizumab (Part 2)

EXPERIMENTAL

Extension cohort at the RP2D of PLX3397 in combination with pembrolizumab in approximately 376 patients with advanced solid tumors (Enrollment Complete- 45 enrolled)

Drug: PLX3397; Biological: Pembrolizumab

Interventions

PLX3397 DRUG

PLX3397 capsules, 200 mg

Also known as: Pexidartinib

PLX3397 and Pembrolizumab (Part 1); PLX3397 and Pembrolizumab (Part 2)

Pembrolizumab BIOLOGICAL

Pembrolizumab, 200 mg, IV

Also known as: Keytruda, MK-3475, SCH 900475

PLX3397 and Pembrolizumab (Part 1); PLX3397 and Pembrolizumab (Part 2)

Eligibility Criteria

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

You may qualify if:

• Subjects with histologically or cytologically-confirmed diagnosis of cancer that is recurrent, metastatic, or persistent, who have relapsed from or are refractory to treatment and who also meet the following corresponding requirements for the cohort or phase of the study into which they will enroll:
• Dose-escalation Phase: Subjects with advanced solid tumors (any tumor type) considered to have no standard-of care treatment for their malignancy with a curative intent, either as initial therapy or after progressing to prior therapies; subjects who have been treated previously with a CSF1R inhibitor or an anti PD1/PDL1 inhibitor may enroll.
• Expansion Phase: Subjects with 1 of the tumor types who have relapsed from or are refractory to standard treatment. Subjects with non-small-cell lung cancer (non-squamous; EGFR, ALK wild type), advanced melanoma, ovarian cancer, unresectable RCC with component of clear-cell histology and/or component of sarcomatoid histology, glioblastoma or gliosarcoma, gastrointestinal stromal tumor.
• Subjects with melanoma must have a histologically confirmed diagnosis of stage III disease not amenable to local therapy. Melanoma subjects may have received any number of prior lines of therapy for metastatic disease and must have measurable disease per RECISTv1.1. Subjects with melanoma who have received prior treatment with a BRAF/MEK inhibitor are acceptable candidates.
• Expansion cohorts: Subjects must have relapsed or been refractory to standard treatment. NSCLC, SCCHN, and Melanoma must show primary progression with antiPD1/anti-PDL1 therapy. They must have tumor accessible for sequential biopsy (core needle biopsy or excision required) and be willing to provide on study tumor tissue biopsy. Subjects for whom newly obtained samples cannot be obtained (e.g. inaccessible or patient safety concern) may submit an archived specimen onlyupon agreement from the Sponsor.
• ECOG performance status 0 or 1.
• Women of childbearing potential must have a negative serum pregnancy test within 72 hours prior to initiation of dosing.
• Women of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication. Women of non-child bearing potential may be included if they are either surgically sterile or have been postmenopausal for ≥1 year.
• Fertile men must agree to use an effective method of birth control starting with the first dose of study treatment through 120 days after the last dose of study treatment.
• Adequate organ function as demonstrated by laboratory values.

You may not qualify if:

• A subject who meets any of the following criteria will be disqualified from entering the study:
• Disease that is suitable for local therapy administered with curative intent.
• Diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment.
• Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 28 days prior to the first dose of study treatment.
• Has had monoclonal antibody within 28 days of first dose of study treatment or has not recovered from AEs due to agents administered more than 28 days earlier.
• Has had chemotherapy, targeted small molecule therapy, or radiation therapy within 14 days prior to first dose of study treatment or who has not recovered from AEs due to a previously administered agent.
• Note: Subjects with ≤ Grade 2 neuropathy or ≤ Grade 2 alopecia are an exception to this criterion and may qualify for the study.
• Note: If a subject received major surgery, he or she must have recovered adequately from the toxicity and/or complications from the intervention prior to starting study treatment.
• Has received transfusion of blood products (including platelets or red blood cells \[RBC\]) or administration of colony stimulating factors (including granulocyte colony-stimulating factor, granulocyte macrophage colony-stimulating factor, or recombinant erythropoietin) within 28 days prior to Day 1.
• Evidence of interstitial lung disease or active, noninfectious pneumonitis.
• Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin that has undergone potentially curative therapy, in situ cervical cancer and isolated elevation of prostate-specific antigen. Subjects with a completely treated prior malignancy with no evidence of disease for ≥ 2 years are eligible.
• For Expansion cohort subjects who have previously received an anti-PD-1, anti-PD-L1, or anti#PD-L2 agent or has previously participated in pembrolizumab clinical trials are excluded, except the following tumor types Melanoma, NSCLC and SCCHN (who must show primary progression to anti-PD1/anti-PDL1 therapy).
• Radiation therapy within 14 days of first dose of study treatment.- remove since it's repetitive
• Has active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy is not considered a form of systemic treatment.
• Has an active infection requiring systemic therapy.

Sponsors & Collaborators

• Daiichi Sankyo: lead
• Plexxikon: collaborator
• Merck Sharp & Dohme LLC: collaborator

Study Sites (12)

HonorHealth Research Institute

Scottsdale, Arizona, 85258, United States

Location

Marin Cancer Care

Greenbrae, California, 94904, United States

Location

Ronald Reagan UCLA Medical Center

Los Angeles, California, 90095, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02115, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Washington University St. Louis Siteman Cancer Center

St Louis, Missouri, 63130, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Medical University Health Hollings Cancer Center

Charleston, South Carolina, 29425, United States

Location

Vanderbilt Ingram Cancer Center

Nashville, Tennessee, 37212, United States

Location

South Texas Accelerated Research Therapeutics

San Antonio, Texas, 78229, United States

Location

MeSH Terms

Conditions

Melanoma; Carcinoma, Non-Small-Cell Lung; Squamous Cell Carcinoma of Head and Neck; Gastrointestinal Stromal Tumors; Ovarian Neoplasms

Interventions

pexidartinib; pembrolizumab

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Head and Neck Neoplasms; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Endocrine Gland Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders

Limitations and Caveats

Enrollment for this study was terminated early for insufficient evidence of clinical efficacy. Some of the planned statistical analyses described in the protocol and Statistical Analysis Plan (SAP) were not performed.

Results Point of Contact

• Title: Medical Director
• Organization: Daiichi Sankyo Inc.

CTRinfo@dsi.com

908-992-6400

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

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: May 20, 2015
• First Posted: May 22, 2015
• Study Start: July 2, 2015
• Primary Completion: August 17, 2018
• Study Completion: October 12, 2018
• Last Updated: March 5, 2020
• Results First Posted: October 9, 2019

Record last verified: 2020-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: Studies for which the medicine and indication have received European Union (EU) and United States (US), and/or Japan (JP) marketing approval on or after 01 January 2014 or by the US or EU or JP Health Authorities when regulatory submissions in all regions are not planned and after the primary study results have been accepted for publication.
• Access Criteria: Formal request from qualified scientific and medical researchers on IPD and clinical study documents from clinical trials supporting products submitted and licensed in the United States, the European Union and/or Japan from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent.

Locations

US (12)