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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02452424
Recruitment Status : Completed
First Posted : May 22, 2015
Last Update Posted : November 15, 2018
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):

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

Condition or disease Intervention/treatment Phase
Melanoma Non-small Cell Lung Cancer Squamous Cell Carcinoma of the Head and Neck Gastrointestinal Stromal Tumor (GIST) Ovarian Cancer Drug: PLX3397 Biological: Pembrolizumab Phase 1 Phase 2

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 78 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase 1/2a Study of Double-Immune Suppression Blockade By Combining a CSF1R Inhibitor (PLX3397) With An Anti-PD-1 Antibody (Pembrolizumab) To Treat Advanced Melanoma And Other Solid Tumors
Study Start Date : June 2015
Actual Primary Completion Date : August 2018
Actual Study Completion Date : August 2018

Arm Intervention/treatment
Experimental: PLX3397 and Pembrolizumab

Part 1: Open-label, sequential PLX3397 dose escalation with a fixed dose of pembrolizumab in approximately 24 patients with advanced solid tumors.

(Enrollment complete- 33 enrolled)

Part 2: 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
PLX3397 capsules, 200 mg

Biological: Pembrolizumab
Pembrolizumab, 200 mg, IV
Other Name: Keytruda, MK-3475, SCH 900475

Primary Outcome Measures :
  1. Safety of PLX3397 in combination with Pembrolizumab [ Time Frame: 1 year ]
    Safety of PLX3397 in combination with pembrolizumab will be assessed by reported adverse events.

Secondary Outcome Measures :
  1. Objective response rate [ Time Frame: 1 year ]
    Objective response as measured by the proportion of patients who achieve a complete response (CR) or partial response (PR) by RECIST v1.1 relative to the historical control.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

A subject must satisfy all of the following criteria to be considered for inclusion in the study:

  • 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 advanced melanoma, non-small-cell lung cancer (non-squamous; EGFR, ALK wild type), squamous cell carcinoma of the head and neck, ovarian cancer, or 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 only upon agreement from the Sponsor.
  • ECOG performance status 0 or 1.
  • Adequate organ function as demonstrated by laboratory values.

Exclusion Criteria:

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.
  • 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.
  • Has known central nervous system metastases and/or carcinomatous meningitis.

    o Note: Subjects with previously treated brain metastases may participate if they meet the following criteria: 1) are stable for at least 28 days prior to the first dose of study treatment and if all neurologic symptoms returned to baseline); 2) have no evidence of new or enlarging brain metastases; and 3) have not been using steroids for at least 7 days prior to first dose of study treatment. This exception does not include carcinomatous meningitis, which is excluded regardless of clinical stability.

  • Uncontrolled intercurrent illness.
  • Refractory nausea and vomiting, malabsorption, external biliary shunt, or significant small bowel resection that would preclude adequate absorption.
  • QT interval corrected using Fridericia's formula (QTc) ≥ 450 msec (males) or ≥ 470 msec (females) at Screening.
  • Congenital long QT syndrome or patients taking concomitant medications known to prolong the QT interval.
  • Major surgery within 28 days prior to first dose of study treatment.
  • Has received a live vaccine administered within 30 days prior to first dose of study treatment.
  • Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
  • Active and clinically significant bacterial, fungal or viral infection, including hepatitis B virus (HBV), hepatitis C virus (HCV), known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome related illness (HIV testing is not required), including subjects who have an active infection requiring systemic therapy.
  • Any of the following within 48 weeks (~1 year) prior to first dose of study treatment: myocardial infarction, uncontrolled angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack.
  • Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit through 120 days after the last dose of study treatment.
  • Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
  • Has had prior exposure to PLX3397.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02452424

United States, Arizona
HonorHealth Research Institute
Scottsdale, Arizona, United States, 85258
United States, California
Marin Cancer Care
Greenbrae, California, United States, 94904
Ronald Reagan UCLA Medical Center
Los Angeles, California, United States, 90095
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02115
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02215
United States, Michigan
Karmanos Cancer Institute
Detroit, Michigan, United States, 48201
United States, Missouri
Washington University St. Louis Siteman Cancer Center
Saint Louis, Missouri, United States, 63130
United States, New York
Memorial Sloan Kettering Cancer Center
New York, New York, United States, 10065
United States, South Carolina
Medical University Health Hollings Cancer Center
Charleston, South Carolina, United States, 29425
United States, Tennessee
Vanderbilt Ingram Cancer Center
Nashville, Tennessee, United States, 37212
United States, Texas
South Texas Accelerated Research Therapeutics
San Antonio, Texas, United States, 78229
Sponsors and Collaborators
Merck Sharp & Dohme Corp.

Responsible Party: Plexxikon Identifier: NCT02452424     History of Changes
Other Study ID Numbers: PLX108-14
KEYNOTE-103 ( Other Identifier: Merck Sharp & Dohme Corp. )
First Posted: May 22, 2015    Key Record Dates
Last Update Posted: November 15, 2018
Last Verified: September 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Carcinoma, Squamous Cell
Head and Neck Neoplasms
Gastrointestinal Stromal Tumors
Carcinoma, Bronchogenic
Bronchial Neoplasms
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Nerve Tissue
Nevi and Melanomas
Neoplasms, Glandular and Epithelial
Neoplasms, Squamous Cell
Neoplasms, Connective Tissue
Neoplasms, Connective and Soft Tissue
Gastrointestinal Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Gastrointestinal Diseases