Clinical Trials /

APL-101 Study for NSCLC With c-Met EXON 14 Skip Mutations and c-Met Dysregulation Advance Solid Tumors

NCT03175224

Description:

The primary Phase 1 purpose of this study is to assess overall safety and tolerability and recommended Phase 2 dose (RP2D) of APL-101. The Phase 2 portion will assess efficacy of the dose determined in phase 1 in individuals with Non-Small Cell Lung Cancer with c-Met EXON 14 skip mutations and c-Met Dysregulation Advance Solid Tumors

Related Conditions:
  • Adenocarcinoma of the Gastroesophageal Junction
  • Gastric Carcinoma
  • Malignant Solid Tumor
  • Non-Small Cell Lung Carcinoma
  • Renal Cell Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: CBT-101 Study for Advanced Solid Tumors and c-Met Dysregulation
  • Official Title: Phase 1 Multicenter Study of the Safety, Pharmacokinetics, and Preliminary Efficacy of CBT-101 in Subjects With Advanced Solid Tumors and c-Met Dysregulation

Clinical Trial IDs

  • ORG STUDY ID: CBT-101-01
  • NCT ID: NCT03175224

Conditions

  • Solid Tumor
  • Advanced Cancer
  • Renal Cancer
  • Gastric Cancer
  • Gastroesophageal Junction Adenocarcinoma

Interventions

DrugSynonymsArms
CBT-101 Oral CapsulesBozitinib, PLB-1001, CBI-3103Single-Arm

Purpose

The purpose of this study is to determine the safety, tolerability, and recommended dose of CBT-101 in individuals with advanced solid tumors and c-MET dysregulation.

Detailed Description

      This is a Phase 1, multi-center, open-label, 2-part study with a Dose Escalation Segment and
      Dose and Disease Expansion Cohorts study of CBT-101, a c-MET inhibitor, to determine the
      recommended Phase 2 dose (RP2D) and dose limiting toxicities for CBT-101, and to obtain
      preliminary efficacy and target engagement data, in subjects with advanced malignancies and
      c-Met dysregulation.

      c-MET dysregulation will be determined from historical results by molecular pre-screening
      evaluations to determine eligibility of enrollment for both the Dose Escalation Segment and
      Dose and Disease Expansion Cohorts. However, in the Dose and Disease Expansion Cohorts, the
      c-MET historical results will be confirmed by a central laboratory retrospectively, but will
      not be a determinant for study entry.

      Dose escalation will occur in three subject cohorts until a protocol defined dose limited
      toxicity (DLT) occurs and a tentative maximum tolerated dose (MTD) is determined.

      At the tentative MTD or RP2D, at least 16 additional subjects for each stated tumor type
      (renal cell carcinoma, advanced gastric carcinoma (including gastroesophageal junction
      adenocarcinoma), and a biomarker driven basket of tumors with c-MET dysregulation will be
      assessed to further evaluate toxicity and preliminary efficacy.
    

Trial Arms

NameTypeDescriptionInterventions
Single-ArmExperimentalCBT-101 (Bozitinib) Oral Capsules
  • CBT-101 Oral Capsules

Eligibility Criteria

        Major Inclusion Criteria:

          -  Able to understand and comply with study procedures, understand the risks involved,
             and provide written informed consent.

          -  Dose Escalation Segment: histologically and / or cytological confirmed locally
             advanced, recurrent or relapsed, or metastatic incurable solid malignancy with no
             limit on the number of prior lines of standard therapy.

          -  Dose and Disease Expansion Cohorts: histologically confirmed renal cell carcinoma,
             gastric carcinoma (including gastro-esophageal junction adenocarcinoma), and a
             biomarker driven cohort of tumors with evidence of c-MET dysregulation
             (amplification, mutation)

               -  Renal Cell Carcinoma: documented histological or cytological diagnosis of renal
                  cell cancer with a clearcell or papillary component; progression following at
                  least two prior lines of standard therapy including a checkpoint inhibitor and
                  an anti-VEGFR inhibitor; archival tissue or fresh tumor biopsy

               -  Gastric Carcinoma (including Gastro-Esophageal Junction Adenocarcinoma):
                  progression following at least one prior line of standard therapy that contained
                  a fluoropyrimidine and/or platinum and/or taxane agent; prior adjuvant or
                  neoadjuvant therapy is counted as one regimen, provided that disease progression
                  occurs within 6 months after the completion of adjuvant or neoadjuvant therapy;
                  HER2 negative subjects (defined by HER2 ≤ 2+ by IHC) by medical history;
                  archival tissue or fresh tumor biopsy

          -  Abnormal c-MET dysregulation, defined as the following from archival historical
             results of molecular pre-screening evaluations.

               -  Dose Escalation Segment

                    -  c-MET overexpression, ≥ 50% tumor cells with immunohistochemistry Grade 3+

                    -  or c-MET amplification; c-MET to chromosome 7 (CEP 7) ratio ≥ 2.2

                    -  or mutation (exon 14) (NSCLC only)

               -  Dose and Disease Expansion Cohorts

                    -  c-MET amplification; c-MET to CEP 7 ratio ≥ 2.2

                    -  or mutation (exon 14) (NSCLC only)

          -  Measurable disease according to RECIST v1.1

          -  No chemotherapy treatments within at least 3 weeks prior to first dose of study
             treatment. For all prior anticancer treatment, including radiotherapy or targeted
             agents or hormonal therapy, a duration of more than 5 half-lives of the
             targeted/hormonal agents used must have elapsed, and any encountered toxicity must
             have resolved to levels meeting all the other eligibility criteria.

          -  Adequate cardiac function (≤ NYHA Class II) or normal cardiac function with left
             ventricular ejection fraction (LVEF) ≥ 50% at screening.

        Major Exclusion Criteria:

          -  Hypersensitivity to CBT-101, excipients of the drug product, or other components of
             the study treatment regimen.

          -  History of receiving treatment with any c-MET signaling pathway inhibitor (marketed
             or investigational agents)

          -  History of, or at risk for, cardiac disease (e.g., long QT syndrome [> 450 msec] or
             concurrent treatment with any medication that prolongs QT interval).

          -  Symptomatic primary tumors or metastasis of brain and/or central nervous system,
             uncontrolled with antiepileptic and requiring high doses of steroids.

          -  Unable to swallow orally administered medication whole.

          -  Impairment of gastrointestinal function or gastrointestinal disease that may
             significantly alter drug absorption (e.g., Crohn's, ulcerative colitis, active
             inflammatory bowel disease, uncontrolled nausea, vomiting, diarrhea, or malabsorption
             syndrome).

          -  Radiation therapy for bone metastasis within 2 weeks, any other external radiation
             therapy within 4 weeks before randomization. Systemic treatment with radionuclides
             within 6 weeks before randomization. Subjects with complications from prior radiation
             therapy are not eligible and AEs must return to baseline or ≤ Grade 1.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of participants with treatment related adverse events as assessed by Common Terminology Criteria for Adverse Events (CTCAE v4.03)
Time Frame:From the time of informed consent signature to 30 days after discontinuation of study drug.
Safety Issue:
Description:Adverse events, serious adverse events, and dose limiting toxicities according to the National Cancer Institute (NCI) Terminology Criteria for Adverse Events (CTCAE v4.03)

Secondary Outcome Measures

Measure:Determine the recommended Phase 2 dose and schedule
Time Frame:Approximately 1 year
Safety Issue:
Description:Adverse events, serious adverse events, and dose limiting toxicities according to the National Cancer Institute (NCI) Terminology Criteria for Adverse Events (CTCAE v4.03)
Measure:Area under the plasma concentration versus time curve (AUC)
Time Frame:Up to 2 months (1 cycle = 28 days)
Safety Issue:
Description:AUC, 0 - infinity
Measure:Maximum plasma concentration
Time Frame:Up to 2 months (1 cycle = 28 days)
Safety Issue:
Description:Cmax
Measure:Time to reach Cmax
Time Frame:Up to 2 months (1 cycle = 28 days)
Safety Issue:
Description:Tmax
Measure:Overall Response Rate
Time Frame:Approximately 12 months
Safety Issue:
Description:Anti-tumor activity per RECIST v1.1
Measure:Duration of Response
Time Frame:Approximately 24 months
Safety Issue:
Description:Anti-tumor activity per RECIST v1.1
Measure:Progression Free Survival
Time Frame:Approximately 24 months
Safety Issue:
Description:Anti-tumor activity per RECIST v1.1

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:CBT Pharmaceuticals, Inc.

Trial Keywords

  • Advanced Solid Tumor
  • Relapsed Solid Tumor
  • Recurrent Solid Tumor

Last Updated

June 1, 2017