Clinical Trials /

APL-501 Study for Select Advanced or Relapsed/Recurrent Solid Tumors

NCT03053466

Description:

The purpose of this study is to determine the safety, tolerability, and recommended dose schedule of APL-501 in individuals with advanced or relapsed or recurrent solid tumors.

Related Conditions:
  • Adenocarcinoma of the Gastroesophageal Junction
  • Ampulla of Vater Clear Cell Adenocarcinoma
  • Bladder Clear Cell Adenocarcinoma
  • Carcinoma of Unknown Primary Origin
  • Carcinosarcoma
  • Cervical Carcinoma
  • Cervical Clear Cell Adenocarcinoma
  • Clear Cell Adenocarcinoma
  • Clear Cell Hepatocellular Carcinoma
  • Clear Cell Odontogenic Carcinoma
  • Clear Cell Renal Cell Carcinoma
  • Clear Cell Sarcoma of Soft Tissue
  • Clear Cell Sarcoma of the Kidney
  • Clear Cell Squamous Cell Skin Carcinoma
  • Colorectal Carcinoma
  • Endometrial Carcinoma
  • Endometrial Clear Cell Adenocarcinoma
  • Esophageal Carcinoma
  • Extrahepatic Bile Duct Clear Cell Adenocarcinoma
  • Fallopian Tube Clear Cell Adenocarcinoma
  • Gastric Carcinoma
  • Head and Neck Carcinoma
  • Hepatocellular Carcinoma
  • Hereditary Clear Cell Renal Cell Carcinoma
  • Large Cell Lung Carcinoma, Clear Cell Variant
  • Malignant Ovarian Clear Cell Tumor
  • Malignant Solid Tumor
  • Melanoma
  • Merkel Cell Carcinoma
  • Mesothelioma
  • Non-Small Cell Lung Carcinoma
  • Ovarian Carcinoma
  • Ovarian Clear Cell Tumor
  • Renal Cell Carcinoma
  • Skin Clear Cell Basal Cell Carcinoma
  • Skin Squamous Cell Carcinoma
  • Small Cell Lung Carcinoma
  • Thymic Clear Cell Carcinoma
  • Urethral Clear Cell Adenocarcinoma
  • Urothelial Carcinoma
  • Uterine Ligament Clear Cell Adenocarcinoma
  • Vulvar Clear Cell Hidradenocarcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: CBT-501 Study for Select Advanced or Relapsed/Recurrent Solid Tumors
  • Official Title: A Phase 1 Multicenter, Dose Escalation, Cohort Extension and Dose and Disease Expansion Study of CBT-501 in Subjects With Select Advanced or Relapsed/Recurrent Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: CBT-501-01
  • NCT ID: NCT03053466

Conditions

  • Solid Tumor
  • Advanced Cancers
  • Colorectal Cancer
  • Gastric Cancer
  • Hepatocellular Cancer
  • Non Small Cell Lung Cancer
  • Renal Cancer
  • Head and Neck Squamous Cell Carcinoma
  • CHL
  • Urothelial Carcinoma
  • Gastroesophageal Junction Adenocarcinoma
  • Microsatellite Instability
  • Mismatch Repair Deficiency
  • Esophageal Cancer
  • Cancer of Unknown Primary Site
  • Carcinosarcoma

Interventions

DrugSynonymsArms
CBT-501GB226Single-Arm

Purpose

The purpose of this study is to determine the safety, tolerability, and recommended dose schedule of CBT-501 in individuals with advanced or relapsed or recurrent solid tumors.

Detailed Description

      This is a Phase 1, multicenter, 3-part study with a Dose-Escalation Segment, Cohort Extension
      and Dose and Disease Expansion cohorts of CBT-501 injection, a humanized IgG4 monoclonal
      antibody, targeting the Programmed Death-1 (PD-1) membrane receptor on T lymphocytes and
      other cells of the immune system. Select advanced solid tumor malignancies will receive
      escalating doses of CBT-501.

      Dose escalation will occur in three subject cohorts until a protocol defined dose limited
      toxicity (DLT) occurs, not due to disease progression or inter-current illness, and a
      tentative maximum tolerated dose (MTD) or biologically effective dose (BED) is determined.

      Cohort Extension will evaluate CBT-501 at 3 mg/kg and 10 mg/kg on Day 1 and Day 15 every 28
      days and on Day 1 every 21 days in PD-1 approved labelled indications.

      At the tentative MTD, BED or recommended Phase 2 dose (RP2D), at least four tumor types in
      the Dose and Disease Expansion will be assessed at a equivalent non-weight based dose to
      further evaluate toxicity and preliminary efficacy.
    

Trial Arms

NameTypeDescriptionInterventions
Single-ArmExperimentalCBT-501
  • CBT-501

Eligibility Criteria

        Major Inclusion Criteria:

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

        Dose Escalation:

          -  Histologically and / or cytological confirmed solid tumors: colorectal, endometrial,
             gastric including, gastroesophageal junction adenocarcinoma (GC), head and neck
             (esophageal, hepatocellular (HCC), non-small cell lung cancer, mesothelioma, ovarian,
             and renal cell carcinoma (RCC), either refractory or relapsed to standard therapy or
             for which no effective standard therapy is available.

          -  No restriction to number of prior therapies for Dose Escalation Segment except for
             gastric and renal cell carcinoma.

        Cohort Extension:

          -  Histologically and/or cytological confirmed solid tumors with an approved labelled
             indication for PD-1 inhibitors.

          -  Tumor biopsy at study entry and during therapy. Tumor sites used to satisfy this
             criterion must not have received any prior radiation therapy. Sites for biopsy must be
             distinct from target lesions used for efficacy assessment.

          -  Measurable disease according to RECIST v1.1.

        Dose and Disease Expansion:

          -  MSI-H or dMMR per local laboratory and failed at least one prior line of standard of
             care chemotherapy per local standards.

          -  Carcinoma of unknown primary with at least 1% of PD-L1 expression by IHC per local
             laboratory.

          -  Clear cell histology and carcinosarcomas with at least 1% of PD-L1 expression by IHC
             per local laboratory.

          -  Esophageal carcinoma with advanced or metastatic disease either of adenocarcinoma or
             squamous histology with at least 1% of PD-L1 expression by IHC per local laboratory or
             tumor inflammation signature positive.

        Major Exclusion Criteria:

          -  History of severe hypersensitivity to mAbs, excipients of the drug product or other
             components

          -  Prior malignancy active within the previous 2 years except for locally curable cancers
             that have been cured, such as basal or squamous cell skin cancer, superficial bladder
             cancer or carcinoma in situ of the cervix or breast

          -  Any active autoimmune disease or a documented history of autoimmune disease, or
             history of syndrome that required systemic steroids or immunosuppressive medications,
             except for subjects with vitiligo or resolved childhood asthma/atopy

          -  Prior therapy with an anti-PD-1, anti-PD-L1, anti-PDL-2, or anti-CTLA-4 antibody (or
             any other antibody targeting T cell co-stimulation pathways) (except NSCLC)

          -  Known significant mental illness or other conditions such as active alcohol or other
             substance abuse that, in the opinion of the Investigator, predisposes the subject to
             high risk of noncompliance with the protocol treatment or assessments.
      
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) in patients with advance solid tumors
Time Frame:From the time of informed consent from signature until Day 28 after Cycle 1; Dose Escalation - Approximately 9 months
Safety Issue:
Description:Adverse events, serious adverse events, 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:An average of 1 year
Safety Issue:
Description:adverse events, serious adverse events, dose limiting toxicities
Measure:Area under the plasma concentration versus time curve (AUC)
Time Frame:Up to 4 months (1 cycle = 28 days)
Safety Issue:
Description:AUC, 0-infinity
Measure:Maximum plasma concentration
Time Frame:Up to 4 months (1 cycle = 28 days)
Safety Issue:
Description:Cmax
Measure:Time to reach Cmax
Time Frame:Up to 4 months (1 cycle = 28 days)
Safety Issue:
Description:Tmax
Measure:Objective Response Rate (ORR)
Time Frame:Approximately 24 months
Safety Issue:
Description:The treatment effect of CBT-501 will be assessed by RECIST v1.1 and by irRECIST to determine proportion of patients with complete response or partial response.
Measure:Duration of Response (DOR)
Time Frame:Approximately 24 months
Safety Issue:
Description:The treatment effect of CBT-501 will be assessed by RECIST v1.1 or by irRECIST to determine duration of response. Time from first documented complete response or partial response until subsequent documented disease progression or death.
Measure:Time to Response (TTR)
Time Frame:Approximately 24 months
Safety Issue:
Description:The treatment effect of CBT-501 will be assessed by RECIST v1.1 and by irRECIST to determine time to complete response and partial response.
Measure:Disease Control Rate (DCR)
Time Frame:Approximately 24 months
Safety Issue:
Description:The treatment effect of CBT-501 will be assessed by RECIST v1.1 and irRECIST to determine disease control rate. Proportion of patients with best overall response of complete response, partial response, or stable disease.
Measure:Progression Free Survival
Time Frame:Approximately 24 months
Safety Issue:
Description:The effect of CBT-501 will be assessed by RECIST v1.1 and per irRECIST to determine progression free survival as time from date of first dose to date of disease progression or death.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:CBT Pharmaceuticals (Australia) Pty Ltd

Trial Keywords

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

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