APL-101 Study for NSCLC With c-Met EXON 14 Skip Mutations and c-Met Dysregulation Advance Solid Tumors
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| ClinicalTrials.gov Identifier: NCT03175224 |
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Recruitment Status :
Recruiting
First Posted : June 5, 2017
Last Update Posted : April 8, 2019
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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 Advance Solid Tumors
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Solid Tumor Advanced Cancer Renal Cancer Gastric Cancer Gastroesophageal Junction Adenocarcinoma NSCLC Lung Cancer | Drug: APL-101 Oral Capsules (formerly CBT-101) | Phase 1 Phase 2 |
This is a Phase 1, multi-center, 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 and Dose and Disease Expansion Cohorts. However, in the Dose and Disease Expansion Cohorts, the c-MET historical results will be confirmed by a central laboratory retrospectively, but will not be a determinant for study entry.
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, three cohort groups will be further evaluated: Cohort A: EXON 14 NSCLC (c-Met naïve), Cohort B: EXON 14 NSCLC (c-Met experienced; progressed on prior c-Met inhibitor), Cohort C: basket of tumor types with c-Met dysregulation (amplification or mutation or fusions)
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 110 participants |
| Intervention Model: | Single Group Assignment |
| Intervention Model Description: | Subjects will be assigned to a dose level in the order of study entry. Treatment includes five planned dose levels (100 mg, 200 mg, 300 mg, 400 mg, 550 mg). |
| 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 Advance Solid Tumors |
| Actual Study Start Date : | September 27, 2017 |
| Estimated Primary Completion Date : | September 30, 2021 |
| Estimated Study Completion Date : | December 30, 2021 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: Single-Arm
APL-101 Oral Capsules
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Drug: APL-101 Oral Capsules (formerly CBT-101)
Subjects will be assigned to a dose level of APL-101 in the order of study entry. Treatment includes 28-day cycles at five planned dose levels (100 mg, 200 mg, 300 mg, 400 mg, 550 mg). Each treatment cycle is administered by oral capsules consecutively every 12 hours.
Other Names:
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- Determine the recommended phase 2 dose [ 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 (each cycle is 28 days) ]Anti-tumor activity per RECISTv1.1
- 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
- Correlation of CBT-101 and hepatocyte growth factor at baseline and after study treatment. [ Time Frame: Approximately 24 months ]Blood samples
- Correlation of CBT-101 and soluble c-MET at baseline and after study treatment. [ Time Frame: Approximately 24 months ]Blood samples
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 locally advanced, recurrent or relapsed or metastatic incurable solid malignancy
- For Phase 2, three cohorts will be enrolled: Cohort A: EXON 14 NSCLC (c-Met naïve), Cohort B: EXON 14 NSCLC (c-Met experienced; progressed on prior c-Met inhibitor), Cohort C: basket of tumor types with c-Met dysregulation (amplification or mutation or fusions).
- Measurable disease according to RECIST v1.1. 7.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
- No planned major surgery within 4 weeks of first dose of APL-101
Major Exclusion Criteria:
- Hypersensitivity to CBT-101, excipients of the drug product, or other components of the study treatment regimen.
- Known mutation of EGFR, ALK or ROS1 or have received a kinase inhibitor for these mutations
- History of, or at risk for, cardiac disease (e.g., long QTc syndrome [> 450 msec] or concurrent treatment with any medication that prolongs QT interval).
- Symptomatic primary tumors or metastasis of brain and/or central nervous system, uncontrolled with antiepileptic and requiring high doses of steroids.
- 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 | 650-209-4055 | Lenilyn.Espiritu@apollomicsinc.com | |
| Contact: Gavin Choy, PharmD, MBA | (925) 272-4090 | gavin.choy@cbtpharma.com |
| United States, Arizona | |
| Mayo Clinic | Recruiting |
| Phoenix, Arizona, United States, 85054 | |
| Contact: Pamela McClure Study Coordinator 480-342-6076 Mcclure.pamela@mayo.edu | |
| Principal Investigator: Mahesh K Seetharam, MD | |
| United States, California | |
| University of Southern California / Norris Comprehensive Cancer Center | Recruiting |
| Los Angeles, California, United States, 90033 | |
| Contact: Chi Nguyen Study Coordinator 949-764-6763 chi.nguyen@hoag.org | |
| Principal Investigator: Anthony El-Khoueiry, MD | |
| Univeristy of California San Francisco | Recruiting |
| San Francisco, California, United States, 94115 | |
| Contact: Melissa Lopez Study Coordinator 415-885-7810 melissa.lopez@ucsf.edu | |
| Contact: Kathleen Comerford Study Coordinator Supervisor +1-415-514-6674 Kathleen.Comerford@ucsf.edu | |
| Principal Investigator: Pamela Munster, MD | |
| United States, Florida | |
| Mayo Clinic | Recruiting |
| Jacksonville, Florida, United States, 32224 | |
| Contact: Torsak Vimoktayon Study Coordinator 904-953-2000 Vimoktayon.torsak@mayo.edu | |
| Principal Investigator: Kabir Mody, MD | |
| United States, Minnesota | |
| Mayo Clinic | Recruiting |
| Rochester, Minnesota, United States, 55905 | |
| Contact: Ann Birgin Study Coordinator 507-266-7093 Birgin.ann@mayo.edu | |
| Principal Investigator: Sani H Kizilbash, MD, MPH | |
| United States, Virginia | |
| West Virginia University Cancer Institute | Recruiting |
| Morgantown, Virginia, United States, 26506 | |
| Contact: Sylvia McEwuen Study Coordinator, BSN 304-293-1683 smcewuen@hsc.wvu.edu | |
| Principal Investigator: Patrick Ma, MD | |
| Study Director: | Lynn Manlapaz-Espiritu | Senior Director, Clinical Operations |
Additional Information:
| Responsible Party: | Apollomics Inc. |
| ClinicalTrials.gov Identifier: | NCT03175224 History of Changes |
| Other Study ID Numbers: |
APL-101-01 (CBT-101-01) |
| First Posted: | June 5, 2017 Key Record Dates |
| Last Update Posted: | April 8, 2019 |
| Last Verified: | April 2019 |
| 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 | |
Keywords provided by Apollomics Inc.:
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Advanced Solid Tumor Relapsed Solid Tumor Recurrent Solid Tumor |
Additional relevant MeSH terms:
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Lung Neoplasms Adenocarcinoma Esophageal Neoplasms Kidney Neoplasms Carcinoma, Renal Cell Neoplasms Respiratory Tract Neoplasms Thoracic Neoplasms Neoplasms by Site Lung Diseases Respiratory Tract Diseases Carcinoma |
Neoplasms, Glandular and Epithelial Neoplasms by Histologic Type Gastrointestinal Neoplasms Digestive System Neoplasms Digestive System Diseases Gastrointestinal Diseases Head and Neck Neoplasms Esophageal Diseases Urologic Neoplasms Urogenital Neoplasms Kidney Diseases Urologic Diseases |