Summary

Eligibility
for people ages 18 years and up (full criteria)
Location
at UCSF
Dates
study started
estimated completion

Description

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 Advanced Solid Tumors

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

Details

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)

Keywords

Solid Tumor Advanced Cancer Renal Cancer Gastric Cancer Gastroesophageal Junction Adenocarcinoma NSCLC Lung Cancer Brain Tumor Glioblastoma Multiforme Advanced Solid Tumor Relapsed Solid Tumor Recurrent Solid Tumor Neoplasms Lung Neoplasms Glioblastoma Kidney Neoplasms APL-101 Oral Capsules

Eligibility

For people ages 18 years and up

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.

Locations

  • University of Southern California / Norris Comprehensive Cancer Center accepting new patients
    Los Angeles California 90033 United States
  • Kaiser Permanente - Vallejo accepting new patients
    Vallejo California 94589 United States

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Apollomics Inc.
Links
Company website for Apollomics, Inc.
ID
NCT03175224
Phase
Phase 1/2
Study Type
Interventional
Last Updated