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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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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. |
| ClinicalTrials.gov Identifier: NCT03175224 |
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Recruitment Status :
Recruiting
First Posted : June 5, 2017
Last Update Posted : May 20, 2021
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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 |
| 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 |
| 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 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: Single-Arm
APL-101 Oral Capsules
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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:
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- 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.
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| 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.
- 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
- 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 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.
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-Espiritu | 16502094055 | infomed@apollomicsinc.com | |
| Contact: Scott Houston | 16502094055 | infomed@apollomicsinc.com |
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| Study Director: | Lynn Manlapaz-Espiritu | Sr Director, Clinical Operations |
| Responsible Party: | Apollomics Inc. |
| ClinicalTrials.gov Identifier: | NCT03175224 |
| Other Study ID Numbers: |
APL-101-01 |
| First Posted: | June 5, 2017 Key Record Dates |
| Last Update Posted: | May 20, 2021 |
| Last Verified: | May 2021 |
| 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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