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APL-101 Study of Subjects With NSCLC With c-Met EXON 14 Skip Mutations and c-Met Dysregulation Advanced Solid Tumors (SPARTA)

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ClinicalTrials.gov Identifier: NCT03175224
Recruitment Status : Recruiting
First Posted : June 5, 2017
Last Update Posted : August 25, 2021
Sponsor:
Information provided by (Responsible Party):
Apollomics Inc.

Tracking Information
First Submitted Date  ICMJE June 1, 2017
First Posted Date  ICMJE June 5, 2017
Last Update Posted Date August 25, 2021
Actual Study Start Date  ICMJE September 27, 2017
Estimated Primary Completion Date September 30, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 22, 2021)
  • Estimate the maximum tolerated dose (MTD) and the incidence of DLTs in Phase 1 [ Time Frame: From the time of informed consent signature through Cycle 1 (28 days) completion ]
    Adverse events, serious adverse events, and dose limiting toxicities
  • Objective response rate (ORR = CR + PR) per blinded independent review committee (BIRC) based on RECIST v1.1 (or relevant criteria per tumor type) [ Time Frame: From time of informed consent signature through completion of treatment (1 cycle = 28 days) ]
    Anti-tumor activity per RECIST v1.1 or relevant evaluation criteria per tumor type.
Original Primary Outcome Measures  ICMJE
 (submitted: June 1, 2017)
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. ]
Adverse events, serious adverse events, and dose limiting toxicities according to the National Cancer Institute (NCI) Terminology Criteria for Adverse Events (CTCAE v4.03)
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 22, 2021)
  • Median duration of response (DOR) per BIRC. [ Time Frame: Approximately 2 years ]
    DOR per RECIST v1.1 or relevant evaluation criteria per tumor type.
  • ORR per investigator assessment based on RECIST v1.1. [ Time Frame: Approximately 2 years ]
    ORR per RECIST v1.1 or relevant evaluation criteria per tumor type.
  • Median DOR per investigator assessment. [ Time Frame: Approximately 2 years ]
    DOR per RECIST v1.1 or relevant evaluation criteria per tumor type.
  • Antitumor activity by clinical benefit rate (CR + PR + SD ≥ 4 cycles) based on RECIST v1.1 Median time to progression (TTP). [ Time Frame: Approximately 2 years ]
    Benefit rate per RECIST v1.1 or relevant evaluation criteria per tumor type.
  • Median time to progression (TTP). [ Time Frame: Approximately 2 years ]
    TTP per RECIST v1.1 or relevant evaluation criteria per tumor type.
  • Progression Free Survival (PFS) and overall survival (OS) at 6, 12, 18 and 24 months [ Time Frame: Approximately 3 years ]
    PFS and OS per RECIST v1.1 or relevant evaluation criteria per tumor type.
Original Secondary Outcome Measures  ICMJE
 (submitted: June 1, 2017)
  • Determine the recommended Phase 2 dose and schedule [ Time Frame: Approximately 1 year ]
    Adverse events, serious adverse events, and dose limiting toxicities according to the National Cancer Institute (NCI) Terminology Criteria for Adverse Events (CTCAE v4.03)
  • Area under the plasma concentration versus time curve (AUC) [ Time Frame: Up to 2 months (1 cycle = 28 days) ]
    AUC, 0 - infinity
  • Maximum plasma concentration [ Time Frame: Up to 2 months (1 cycle = 28 days) ]
    Cmax
  • Time to reach Cmax [ Time Frame: Up to 2 months (1 cycle = 28 days) ]
    Tmax
  • Overall Response Rate [ Time Frame: Approximately 12 months ]
    Anti-tumor activity per RECIST v1.1
  • Duration of Response [ Time Frame: Approximately 24 months ]
    Anti-tumor activity per RECIST v1.1
  • Progression Free Survival [ Time Frame: Approximately 24 months ]
    Anti-tumor activity per RECIST v1.1
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures
 (submitted: June 1, 2017)
  • Correlation of CBT-101 and c-MET at baseline and after study treatment. [ Time Frame: Approximately 24 months ]
  • Correlation of CBT-101 and hepatocyte growth factor at baseline and after study treatment. [ Time Frame: Approximately 24 months ]
  • Correlation of CBT-101 and soluble c-MET at baseline and after study treatment. [ Time Frame: Approximately 24 months ]
 
Descriptive Information
Brief Title  ICMJE APL-101 Study of Subjects With NSCLC With c-Met EXON 14 Skip Mutations and c-Met Dysregulation Advanced Solid Tumors
Official Title  ICMJE Phase 1 / 2 Multicenter Study of the Safety, Pharmacokinetics, and Preliminary Efficacy of APL-101 in Subjects With Non-Small Cell Lung Cancer With c-Met EXON 14 Skip Mutations and c-Met Dysregulation Advanced Solid Tumors
Brief Summary

The primary Phase 1 purpose of this study was to assess overall safety, 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; individuals with cancers associated with c-Met amplifications; individuals with cancers associated with c-Met fusion

Detailed Description

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

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

Once dose is determined, five cohort groups will be further evaluated:

  • Cohort A-1: NSCLC EXON 14 skip mutation (c-Met naïve, 1L)
  • Cohort A-2: NSCLC EXON 14 skip mutation (c-Met naïve, 2/3L),
  • Cohort B: NSCLC EXON 14 skip mutation (c-Met experienced; progressed on prior c-Met inhibitor),
  • Cohort C: basket of tumor types (with c-Met high-level amplifications),
  • Cohort D: basket of tumor types (with c-Met fusions)
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description:

Phase 1: Subjects will be assigned to a dose level in the order of study entry. Treatment includes four planned dose levels (100 mg, 200 mg, 300 mg, and 400 mg).

Phase 2: Subjects will receive RP2D at 400mg daily dose (200mg BID).

Masking: None (Open Label)
Masking Description:
Open Label
Primary Purpose: Treatment
Condition  ICMJE
  • Solid Tumor
  • Advanced Cancer
  • Renal Cancer
  • Gastric Cancer
  • Gastroesophageal Junction Adenocarcinoma
  • NSCLC
  • Lung Cancer
  • Brain Tumor
  • Glioblastoma Multiforme
Intervention  ICMJE Drug: APL-101 Oral Capsules

Phase 1 Subjects will be assigned to a dose level of APL-101 in the order of study entry. Treatment includes 28-day cycles at four planned dose levels (100mg, 200mg, 300mg and 400mg). Each treatment cycle is administered by daily oral capsules taken every 12 hours.

Phase 2 Subjects will be given 400mg daily dose (200mg BID) of APL-101 capsules.

Other Names:
  • PLB-1001
  • CBI-3103
  • Bozitinib
  • CBT-101
  • Vebreltinib
Study Arms  ICMJE Experimental: Single-Arm
APL-101 Oral Capsules
Intervention: Drug: APL-101 Oral Capsules
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 Recruiting
Estimated Enrollment  ICMJE
 (submitted: March 2, 2020)
201
Original Estimated Enrollment  ICMJE
 (submitted: June 1, 2017)
68
Estimated Study Completion Date  ICMJE December 30, 2022
Estimated Primary Completion Date September 30, 2021   (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.
  • For Phase 1, histologically and / or cytological confirmed unresectable or metastatic solid malignancy, refractory to standard therapies with no more than three prior lines of therapy.
  • For Phase 2, five cohorts will be enrolled: Cohort A-1: NSCLC EXON 14 skip mutation (c-Met naïve) for first line treatment, Cohort A-2: NSCLC EXON 14 skip mutation (c-Met naïve) pretreated subjects with no more than 3 lines of prior therapy, Cohort B: NSCLC EXON 14 skip mutation (c-Met experienced; radiographic progression on prior c-Met inhibitor), Cohort C: basket of tumor types with c-Met high level amplification (NSCLC EXON 14 skip mutation excluded), Cohort D: basket of tumor type with c-Met fusions.
  • Local/archival result (tissue and/or plasma) of a positive c-Met dysregulation is required (except in Cohort A-1 in the US).
  • Measurable disease according to RECIST v1.1. (or relevant criteria per tumor type).
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
  • For all prior anticancer treatment, including radiotherapy, chemotherapy or targeted agents or hormonal therapy, a duration of more than 30 days or 5 half-lives of the agents used, whichever is shorter, must have elapsed, and any encountered toxicity must have resolved to levels meeting all the other eligibility criteria prior to the first dose of study treatment.
  • No planned major surgery within 4 weeks of first dose of APL-101

Major Exclusion Criteria:

  • Hypersensitivity to APL-101, excipients of the drug product, or other components of the study treatment regimen.
  • Known actionable mutation/gene rearrangement of EGFR (except for Cohort C), ALK, ROS1, RET, NTRK, KRAS, and BRAF.
  • Unstable angina or myocardial infarction within 1 year prior to first dose of APL-101, symptomatic or unstable arrhythmia requiring medical therapy, history of congenital prolonged QT syndrome, prolonged QT interval corrected by Fridericia formula (QTcF) at screening (> 450 msec based on the average of 3 measurements), or concurrent treatment with a medication that is a known risk for prolonging the QT interval.
  • 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).
  • Women who are breastfeeding.
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: Lynn Manlapaz-Espiritu 16502094055 infomed@apollomicsinc.com
Contact: Anna Nekhymchuk 16502094055 infomed@apollomicsinc.com
Listed Location Countries  ICMJE Australia,   Canada,   Finland,   France,   Hungary,   Italy,   Puerto Rico,   Russian Federation,   Singapore,   Spain,   Taiwan,   Ukraine,   United Kingdom,   United States
Removed Location Countries Hong Kong
 
Administrative Information
NCT Number  ICMJE NCT03175224
Other Study ID Numbers  ICMJE APL-101-01
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Apollomics Inc.
Study Sponsor  ICMJE Apollomics Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Mark Awad, M.D. Dana-Farber Cancer Institute
PRS Account Apollomics Inc.
Verification Date August 2021

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