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APL-501 Study for Select Advanced or Relapsed/Recurrent 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.
 
ClinicalTrials.gov Identifier: NCT03053466
Recruitment Status : Active, not recruiting
First Posted : February 15, 2017
Last Update Posted : June 6, 2019
Sponsor:
Collaborators:
Novotech (Australia) Pty Limited
Apollomics Inc. (formerly CBT Pharmaceuticals, Inc.)
Information provided by (Responsible Party):
Apollomics (Australia) Pty. Ltd.

Tracking Information
First Submitted Date  ICMJE January 30, 2017
First Posted Date  ICMJE February 15, 2017
Last Update Posted Date June 6, 2019
Actual Study Start Date  ICMJE March 27, 2017
Estimated Primary Completion Date February 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 12, 2017)
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 ]
Adverse events, serious adverse events, dose limiting toxicities according to the National Cancer Institute (NCI) Terminology Criteria for Adverse Events (CTCAE v4.03)
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 20, 2019)
  • Determine the recommended Phase 2 dose and schedule [ Time Frame: An average of 1 year ]
    adverse events, serious adverse events, dose limiting toxicities
  • Area under the plasma concentration versus time curve (AUC) [ Time Frame: Up to 4 months (1 cycle = 28 days) ]
    AUC, 0-infinity
  • Maximum plasma concentration [ Time Frame: Up to 4 months (1 cycle = 28 days) ]
    Cmax
  • Time to reach Cmax [ Time Frame: Up to 4 months (1 cycle = 28 days) ]
    Tmax
  • Objective Response Rate (ORR) [ Time Frame: Approximately 24 months ]
    The treatment effect of APL-501 will be assessed by RECIST v1.1 and by irRECIST to determine proportion of patients with complete response or partial response.
  • Duration of Response (DOR) [ Time Frame: Approximately 24 months ]
    The treatment effect of APL-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.
  • Time to Response (TTR) [ Time Frame: Approximately 24 months ]
    The treatment effect of APL-501 will be assessed by RECIST v1.1 and by irRECIST to determine time to complete response and partial response.
  • Disease Control Rate (DCR) [ Time Frame: Approximately 24 months ]
    The treatment effect of APL-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.
  • Progression Free Survival [ Time Frame: Approximately 24 months ]
    The effect of APL-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.
Original Secondary Outcome Measures  ICMJE
 (submitted: February 12, 2017)
  • Determine the recommended Phase 2 dose and schedule [ Time Frame: An average of 1 year ]
    adverse events, serious adverse events, dose limiting toxicities
  • Area under the plasma concentration versus time curve (AUC) [ Time Frame: Up to 4 months (1 cycle = 28 days) ]
    AUC, 0-infinity
  • Maximum plasma concentration [ Time Frame: Up to 4 months (1 cycle = 28 days) ]
    Cmax
  • Time to reach Cmax [ Time Frame: Up to 4 months (1 cycle = 28 days) ]
    Tmax
  • Overall Objective Response Rate [ Time Frame: Approximately 12 months ]
    Antitumor activity per RECIST v1.1 and by irRECIST
  • Duration of Response [ Time Frame: Approximately 24 months ]
    Antitumor activity per RECIST v1.1
  • Time to Response [ Time Frame: Approximately 12 months ]
    Antitumor activity per irRECIST
  • Disease Control Rate [ Time Frame: Approximately 24 months ]
    Antitumor activity per RECIST v1.1
  • Progression Free Survival [ Time Frame: Approximately 24 months ]
    Antitumor activity per RECIST v1.1 and per irRECIST, deaths from any cause
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures
 (submitted: February 12, 2017)
  • Correlation of tumor-infiltrating lymphocyte counts at baseline and post administration of CBT-501 [ Time Frame: Approximately 24 months ]
  • Correlation of PD-1 and PD-L1 expression at baseline to clinical response [ Time Frame: Approximately 24 months ]
  • PD-1 receptor occupancy of CBT-501 [ Time Frame: Up to 6 months ]
  • Degree of immunogenicity of CBT-501 [ Time Frame: Approximately 24 months ]
 
Descriptive Information
Brief Title  ICMJE APL-501 Study for Select Advanced or Relapsed/Recurrent Solid Tumors
Official Title  ICMJE A Phase 1 Multicenter, Dose Escalation, Cohort Extension and Dose and Disease Expansion Study of APL-501 in Subjects With Select Advanced or Relapsed/Recurrent Solid Tumors
Brief Summary 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.
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 APL-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 APL-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 APL-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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Masking Description:
Open Label
Primary Purpose: Treatment
Condition  ICMJE
  • 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
Intervention  ICMJE Drug: APL-501

Subjects will be assigned to a dose level in the order of study entry. Treatment includes a minimum of four 28-day cycles at three planned dose levels (1, 3, and 10 mg/kg). In the Dose Escalation Segment, each treatment cycle is comprised of 2 doses of study drug administered on Days 1 and 15 of a 28-day cycle. In the Cohort Extension, the treatment cycle will consist of 2 doses of study drug administered on Days 1 and 15 of a 28-day cycle and 1 dose of study drug administered on Day 1 of a 21-day cycle.

In Dose and Disease Expansion, the treatment cycle will consist of 2 doses of study drug (non-weight based dosing of 400 mg) administered on Days 1 and 15 of a 28-day cycle.

Other Name: GB226
Study Arms  ICMJE Experimental: Single-Arm
APL-501
Intervention: Drug: APL-501
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: September 9, 2018)
114
Original Estimated Enrollment  ICMJE
 (submitted: February 12, 2017)
50
Estimated Study Completion Date  ICMJE December 2021
Estimated Primary Completion Date February 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03053466
Other Study ID Numbers  ICMJE APL-501-01
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Apollomics (Australia) Pty. Ltd.
Study Sponsor  ICMJE Apollomics (Australia) Pty. Ltd.
Collaborators  ICMJE
  • Novotech (Australia) Pty Limited
  • Apollomics Inc. (formerly CBT Pharmaceuticals, Inc.)
Investigators  ICMJE
Study Chair: Fabio Benedetti, MD Chief Medical Officer
PRS Account Apollomics (Australia) Pty. Ltd.
Verification Date September 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP