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 |
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Recruitment Status :
Recruiting
First Posted : June 5, 2017
Last Update Posted : October 8, 2020
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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 (100 mg, 200 mg, 300 mg and 400 mg). 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
- 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
- Progression Free Survival [ Time Frame: Approximately 24 months ]Anti-tumor activity per RECIST v1.1
- Overall Survival [ Time Frame: Approximately 24 months ]Anti-tumor activity per RECIST v1.1
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.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
- No chemotherapy treatments within at least 3 weeks prior to 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.
- History of, or currently, or at risk for, cardiac disease (e.g., long QT syndrome [> 450 msec QTcF or concurrent treatment with any medication that prolongs 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: Sabine Tricon | 1.650.209.6672 | sabine.tricon@apollomicsinc.com | |
| Contact: Scott Houston | 1.650.492.5334 | Scott.Houston@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 (CBT-101-01) |
| First Posted: | June 5, 2017 Key Record Dates |
| Last Update Posted: | October 8, 2020 |
| Last Verified: | August 2020 |
| 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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Advanced Solid Tumor Relapsed Solid Tumor Recurrent Solid Tumor |
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