Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.
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 (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
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.
- No planned major surgery within 4 weeks of first dose of APL-101
- Expected survival (life expectancy) ≥ 3 months from C1D1.
Major Exclusion Criteria:
- 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.
- 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).
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.
- Women who are breastfeeding.
Eligibility last updated 5/25/22. Questions regarding updates should be directed to the study team contact.