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 : May 20, 2021
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 Advanced Solid Tumors
|Condition or disease||Intervention/treatment||Phase|
|Solid Tumor Advanced Cancer Renal Cancer Gastric Cancer Gastroesophageal Junction Adenocarcinoma NSCLC Lung Cancer Brain Tumor Glioblastoma Multiforme||Drug: APL-101 Oral Capsules||Phase 1 Phase 2|
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 :||Interventional (Clinical Trial)|
|Estimated Enrollment :||201 participants|
|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|
|Official Title:||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|
|Actual Study Start Date :||September 27, 2017|
|Estimated Primary Completion Date :||September 30, 2021|
|Estimated Study Completion Date :||December 30, 2022|
APL-101 Oral Capsules
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.
- Estimate the maximum tolerated dose (MTD) and the incidence of DLTs [ Time Frame: From the time of informed consent signature through Cycle 1 (28 days) completion ]Adverse events, serious adverse events, and dose limiting toxicities
- Determine response rate in Phase 2 [ Time Frame: From time of informed consent signature through completion of Cycle 2 (1 cycle = 28 days) ]Anti-tumor activity per RECIST v1.1 or relevant evaluation criteria per tumor type.
- Incidence of SAE and AEs [ 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
- Duration of Response [ Time Frame: Approximately 24 months ]Anti-tumor activity per RECIST v1.1 or relevant evaluation criteria per tumor type.
- Progression Free Survival [ Time Frame: Approximately 24 months ]Anti-tumor activity per RECIST v1.1 or relevant evaluation criteria per tumor type.
- Overall Survival [ Time Frame: Approximately 24 months ]Anti-tumor activity per RECIST v1.1 or relevant evaluation criteria per tumor type.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03175224
|Contact: Lynn Manlapaz-Espirituemail@example.com|
|Contact: Scott Houstonfirstname.lastname@example.org|
|Study Director:||Lynn Manlapaz-Espiritu||Sr Director, Clinical Operations|