Clinical Trials /

COM701 in Subjects With Advanced Solid Tumors

NCT03667716

Description:

This is a Phase 1 open label sequential dose escalation and cohort expansion study evaluating the safety, tolerability and preliminary clinical activity of COM701 as monotherapy and in combination with a programmed cell death protein 1 (PD-1) inhibitor.

Related Conditions:
  • Breast Adenocarcinoma
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: COM701 in Subjects With Advanced Solid Tumors
  • Official Title: A Phase 1a/1b Study of COM701 as Monotherapy and In Combination With an Anti-PD-1 Antibody in Subjects With Advanced Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: CPG-01-001
  • NCT ID: NCT03667716

Conditions

  • Advanced Cancer
  • Ovarian Cancer
  • Breast Cancer
  • Lung Cancer
  • Endometrial Cancer
  • Ovarian Neoplasm
  • Triple Negative Breast Cancer
  • Lung Neoplasm
  • Neoplasm Malignant

Interventions

DrugSynonymsArms
COM701P1a Arm A (Monotherapy Dose Escalation).
COM701 with a PD-1 inhibitor.P1a Arm B (Combination Dose Escalation).

Purpose

This is a Phase 1 open label sequential dose escalation and cohort expansion study evaluating the safety, tolerability and preliminary clinical activity of COM701 as monotherapy and in combination with a programmed cell death protein 1 (PD-1) inhibitor.

Detailed Description

      This Phase 1 study evaluates the safety, tolerability, Pharmacokinetics (PK) and preliminary
      clinical activity of COM701 an inhibitor of poliovirus receptor related immunoglobulin domain
      containing (PVRIG) as monotherapy and in combination with a PD-1 inhibitor in subjects with
      advanced solid tumors. Cohort expansion in subjects with the following select tumor types
      (Non-Small cell lung cancer (NSCLC), Ovarian, Breast (including Triple negative breast cancer
      (TNBC) and Endometrial cancer) evaluating COM701 monotherapy and in combination with a PD-1
      inhibitor will be explored.
    

Trial Arms

NameTypeDescriptionInterventions
P1a Arm A (Monotherapy Dose Escalation).ExperimentalCOM701 monotherapy sequential dose escalation administered IV every 3 weeks. Up to 7 dose escalation cohorts may be evaluated until a maximum tolerated dose or recommended phase 2 dose is identified.
  • COM701
P1a Arm B (Combination Dose Escalation).ExperimentalCOM701 sequential dose escalation administered IV every 3 weeks in combination with the standard of care (SOC) approved dose of a PD-1 inhibitor administered IV every 3 weeks.
  • COM701
  • COM701 with a PD-1 inhibitor.
P1a Arm A (Monotherapy Expansion).ExperimentalCOM701 monotherapy administered IV every 3 weeks. Cohort expansion in subjects with the following select tumor types (NSCLC, Breast, Ovarian and Endometrial cancer).
  • COM701
P1b (Combination Cohort Dose Expansion).ExperimentalCOM701 administered IV every 3 weeks in combination with the standard of care (SOC) approved dose of a PD-1 inhibitor administered IV every 3 weeks. Cohort expansion in subjects with the following select tumor types (NSCLC, Breast, Ovarian and Endometrial cancer).
  • COM701
  • COM701 with a PD-1 inhibitor.

Eligibility Criteria

        Key Inclusion Criteria:

          -  Subject has Eastern Cooperative Oncology Group (ECOG) performance status 0-1.

          -  Subjects who received prior immune-stimulatory antitumor agents, such as anti-PD-1,
             anti-PD-L1, anti-CTLA-4, OX-40, CD137, etc. are eligible.

          -  Histologically or cytologically confirmed, locally advanced or metastatic solid
             malignancy and has exhausted all the available standard therapy or is not a candidate
             for the available standard therapy.

        Select Tumor Types (COM701 monotherapy cohort expansion; COM701 in combination with a PD-1
        inhibitor):

          -  Breast cancer (TNBC): Histologically confirmed incurable, advanced estrogen receptor-,
             progesterone receptor-, and human epidermal growth factor receptor 2 (HER2)-negative
             (triple-negative) adenocarcinoma of the breast, as defined by the American Society of
             Clinical Oncology-College of American Pathologists (ASCO-CAP) guidelines. Disease
             recurrence or progression during or after at least one systemic treatment that
             included an anthracycline and/or a taxane in the neoadjuvant, adjuvant, or metastatic
             setting. Subjects must have progressed after a poly ADP-ribose polymerase (PARP)
             inhibitor for patients with deleterious or suspected deleterious germline breast
             cancer susceptibility gene (BRCA) mutated metastatic breast cancer.

          -  Endometrial cancer: Subjects with locally advanced or metastatic endometrial cancer,
             Disease recurrence or progression during or after prior therapy that included
             platinum-based chemotherapy.

          -  Ovarian cancer: Disease recurrence or progression during or after prior therapy that
             included: surgical resection, platinum agent, PARP inhibitor (for subjects with
             deleterious or suspected deleterious germline BRCA-mutated advanced ovarian cancer or
             as a maintenance therapy for subjects who have had complete or partial response to
             platinum-based therapy).

          -  NSCLC: Documented stage IIIB or IV or recurrent NSCLC, Disease recurrence or
             progression during or after prior treatment that included: platinum agent, targeted
             therapy such as a TKI (if with biopsy-confirmed cytogenetic mutation eg EGFR, ROS,
             BRAF).

          -  For Phase 1a monotherapy expansion and Phase 1b only: subject has at least one
             measurable lesion that could be followed during the study according to RECIST v1.1.

        Key Exclusion Criteria:

          -  Active autoimmune disease requiring systemic therapy in the last 2 years prior to the
             first dose of COM701.

          -  Symptomatic interstitial lung disease or inflammatory pneumonitis.

          -  History of immune-related events that lead to immunotherapy treatment discontinuation.

          -  Untreated or symptomatic central nervous system (CNS) metastases.

          -  Impaired cardiac function or clinically significant cardiac disease, including any of
             the following: a) Unstable angina pectoris ≤ 6 months prior to first scheduled dose of
             COM701; b) Acute myocardial infarction ≤ 6 months prior to first scheduled dose of
             COM701.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of subjects with Adverse Events (AEs) as per CTCAE v4.03 and Dose-Limiting Toxicities (DLTs).
Time Frame:DLT evaluation window in the 1st cycle (21 Days).
Safety Issue:
Description:To evaluate the safety profile of COM701 monotherapy and in combination with a PD-1 inhibitor.

Secondary Outcome Measures

Measure:Incidence of subjects with Anti-COM701 antibody.
Time Frame:Approximately 2 years.
Safety Issue:
Description:Immunogenicity of COM701 monotherapy and in combination with a PD-1 inhibitor.
Measure:Overall Response Rate as per RECIST v1.1
Time Frame:Approximately 2 years.
Safety Issue:
Description:Preliminary antitumor activity of COM701 in combination with a PD-1 inhibitor.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Compugen Ltd

Trial Keywords

  • PVRIG
  • advanced cancer
  • checkpoint inhibitor
  • DNAM (DNAX Accessory molecule 1)
  • PD-1 inhibitor
  • CD112
  • CD 112R
  • Poliovirus receptor-related immunoglobulin
  • PVRL2

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