Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

APL-101 Study for NSCLC With c-Met EXON 14 Skip Mutations and c-Met Dysregulation Advance Solid Tumors

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
Recruitment Status : Recruiting
First Posted : June 5, 2017
Last Update Posted : April 8, 2019
Sponsor:
Information provided by (Responsible Party):
Apollomics Inc.

Brief Summary:

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

Detailed Description:

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)


Layout table for study information
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
Experimental: Single-Arm
APL-101 Oral Capsules
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:
  • PLB-1001
  • CBI-3103
  • Bozitinib




Primary Outcome Measures :
  1. 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

  2. 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


Secondary Outcome Measures :
  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)

  2. Area under the plasma concentration versus time curve (AUC) [ Time Frame: Up to 2 months (1 cycle = 28 days) ]
    AUC, 0 - infinity

  3. Maximum plasma concentration [ Time Frame: Up to 2 months (1 cycle = 28 days) ]
    Cmax

  4. Time to reach Cmax [ Time Frame: Up to 2 months (1 cycle = 28 days) ]
    Tmax

  5. Duration of Response [ Time Frame: Approximately 24 months ]
    Anti-tumor activity per RECIST v1.1

  6. Progression Free Survival [ Time Frame: Approximately 24 months ]
    Anti-tumor activity per RECIST v1.1


Other Outcome Measures:
  1. Correlation of CBT-101 and hepatocyte growth factor at baseline and after study treatment. [ Time Frame: Approximately 24 months ]
    Blood samples

  2. Correlation of CBT-101 and soluble c-MET at baseline and after study treatment. [ Time Frame: Approximately 24 months ]
    Blood samples



Information from the National Library of Medicine

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.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

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


Contacts
Layout table for location contacts
Contact: Lynn Manlapaz-Espiritu 650-209-4055 Lenilyn.Espiritu@apollomicsinc.com
Contact: Gavin Choy, PharmD, MBA (925) 272-4090 gavin.choy@cbtpharma.com

Locations
Layout table for location information
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         
Sponsors and Collaborators
Apollomics Inc.
Investigators
Layout table for investigator information
Study Director: Lynn Manlapaz-Espiritu Senior Director, Clinical Operations

Additional Information:
Layout table for additonal 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

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Apollomics Inc.:
Advanced Solid Tumor
Relapsed Solid Tumor
Recurrent Solid Tumor

Additional relevant MeSH terms:
Layout table for MeSH terms
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