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 : July 27, 2022
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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
|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, seven 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 except primary CNS tumors with c-Met high-level amplifications (MET inhibitor naive)
- Cohort C-1:NSCLC harboring MET amplification and wild-type EGFR (MET inhibitor naive)
- Cohort D: basket of tumor types except primary CNS tumors harboring c-Met fusions (MET inhibitor naive)
- Cohort E: Primary CNS tumors with MET alterations (MET inhibitor naive)
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||344 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). In Cohort E, the dose may be increased up to 300 mg BID starting at C2D1.Subjects with prior IO therapy within 90 days of study drug start will start at 100mg 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 :||March 30, 2026|
|Estimated Study Completion Date :||November 30, 2026|
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 in Phase 1 (Completed) [ 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.
- 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.
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|Ages Eligible for Study:||18 Years and older (Adult, Older Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
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 (Completed).
- For Phase 2, seven 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 (except Primary CNS tumors), Cohort C-1: NSCLC harboring MET amplification and wild-type epidermal growth factor receptor (EGFR) with no more than 3 lines of prior therapy (MET Naive), Cohort D: basket of tumor types except for primary CNS tumors harboring MET gene fusions (e.g., NSCLC, upper GI, colorectal, hepatobiliary cancer). Previously treated; or previously untreated but refused standard treatment, or if treatment was unavailable or unfeasible (≤ 3 prior lines in unresectable or metastatic setting). Met naive, Cohort E: Primary CNS tumors with MET alterations (single or co-occurred MET fusion including PTPRZ1-MET [ZM] fusion, MET Exon 14 skipping mutation, or MET amplification).Previously treated or previously untreated but refused standard treatment, or if treatment was unavailable or unfeasible (≤ 3 prior lines), Met naive.
- Local/archival result (tissue and/or plasma) of a positive c-Met dysregulation is required (except in Cohort A-1 in the US and Cohort C-1).
In Phase 2, provision of either archival or a fresh tumor biopsy sample (if safe and feasible) either from the primary or a metastatic site is required for study entry for Cohorts A-1, A-2, C, C-1, and D.
- Measurable disease according to relevant criteria (RECIST v1.1, RANO for CNS tumors, or other relevant criteria per tumor type).
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 and/or Karnofsky Performance Scale (KPS) score.
- 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. Palliative radiotherapy to non-target lesions should be completed within 2 weeks prior to APL-101 administration.
- No planned major surgery within 4 weeks of first dose of APL-101
- Expected survival (life expectancy) ≥ 3 months from C1D1.
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).
Symptomatic and/or neurologically unstable CNS metastases, or who require an increase in steroid dose to control CNS disease. Subjects who have been receiving a stable steroid dose for at least 2 weeks prior to C1D1 may be allowed.
- Women who are breastfeeding.
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: Vivian Hueyfirstname.lastname@example.org|
|Study Director:||Marietta Franco||Apollomics Inc.|
|Responsible Party:||Apollomics Inc.|
|Other Study ID Numbers:||
|First Posted:||June 5, 2017 Key Record Dates|
|Last Update Posted:||July 27, 2022|
|Last Verified:||July 2022|
|Individual Participant Data (IPD) Sharing Statement:|
|Plan to Share IPD:||No|
|Studies a U.S. FDA-regulated Drug Product:||Yes|
|Studies a U.S. FDA-regulated Device Product:||No|
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Neoplasms by Histologic Type
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