APL-101 Study of Subjects With NSCLC With c-Met EXON 14 Skip Mutations and c-Met Dysregulation Advanced Solid Tumors (SPARTA)

  • STATUS
    Recruiting
  • End date
    Nov 30, 2026
  • participants needed
    344
  • sponsor
    Apollomics Inc.
Updated on 11 August 2022
cancer
measurable disease
growth factor
lung cancer
major surgery
epidermal growth factor receptor
EGFR
solid tumors
c-MET
cancer chemotherapy
solid tumour
epidermal growth factor
solid neoplasm
lung carcinoma

Summary

The primary Phase 1 purpose of this study was to assess overall safety, 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; individuals with cancers associated with c-Met amplifications; individuals with cancers associated with c-Met fusion

Description

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, seven 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 except primary CNS tumors with c-Met high-level amplifications (MET inhibitor naive)
  • Cohort C-1:NSCLC harboring MET amplification and wild-type EGFR (MET inhibitor naive)
  • Cohort D: basket of tumor types except primary CNS tumors harboring c-Met fusions (MET inhibitor naive)
  • Cohort E: Primary CNS tumors with MET alterations (MET inhibitor naive)

Details
Condition Solid Tumor, Advanced Cancer, Renal Cancer, Gastric Cancer, Gastroesophageal Junction Adenocarcinoma, NSCLC, Lung Cancer, Brain Tumor, Glioblastoma Multiforme
Treatment CBT-101 Oral Capsules, APL-101 Oral Capsules (formerly CBT-101), APL-101 Oral Capsules
Clinical Study IdentifierNCT03175224
SponsorApollomics Inc.
Last Modified on11 August 2022

Eligibility

Yes No Not Sure

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 (Completed)
For Phase 2, seven 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 (except Primary CNS tumors), Cohort C-1: NSCLC harboring MET
No planned major surgery within 4 weeks of first dose of APL-101
amplification and wild-type epidermal growth factor receptor (EGFR) with no more than 3
lines of prior therapy (MET Naive), Cohort D: basket of tumor types except for primary CNS
tumors harboring MET gene fusions (e.g., NSCLC, upper GI, colorectal, hepatobiliary
cancer). Previously treated; or previously untreated but refused standard treatment, or if
treatment was unavailable or unfeasible (≤ 3 prior lines in unresectable or metastatic
setting). Met naive, Cohort E: Primary CNS tumors with MET alterations (single or
co-occurred MET fusion including PTPRZ1-MET [ZM] fusion, MET Exon 14 skipping mutation, or
MET amplification).Previously treated or previously untreated but refused standard
treatment, or if treatment was unavailable or unfeasible (≤ 3 prior lines), Met naive
Local/archival result (tissue and/or plasma) of a positive c-Met dysregulation is
required (except in Cohort A-1 in the US and Cohort C-1)
In Phase 2, provision of either archival or a fresh tumor biopsy sample (if safe and
feasible) either from the primary or a metastatic site is required for study entry for
Cohorts A-1, A-2, C, C-1, and D
Measurable disease according to relevant criteria (RECIST v1.1, RANO for CNS tumors
or other relevant criteria per tumor type)
Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 and/or Karnofsky
Performance Scale (KPS) score
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. Palliative radiotherapy to non-target lesions should be
completed within 2 weeks prior to APL-101 administration
Expected survival (life expectancy) ≥ 3 months from C1D1

Exclusion Criteria

Unable to swallow orally administered medication whole
Women who are breastfeeding
Hypersensitivity to APL-101, excipients of the drug product, or other components of
the study treatment regimen
Known actionable 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
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)
Symptomatic and/or neurologically unstable CNS metastases, or who require an increase in
steroid dose to control CNS disease. Subjects who have been receiving a stable steroid dose
for at least 2 weeks prior to C1D1 may be allowed
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