APL-101 Study of Subjects With NSCLC With c-Met EXON 14 Skip Mutations and c-Met Dysregulation Advanced Solid Tumors (SPARTA)
Solid Tumors, Advanced Cancer, Renal Cancer
About this trial
This is an interventional treatment trial for Solid Tumors focused on measuring Advanced Solid Tumor, Relapsed Solid Tumor, Recurrent Solid Tumor, cMet exon 14 skipping, cMet fusion, GBM, HGF, EGFR positive
Eligibility 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 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.
Sites / Locations
- Loma Linda University Medical Center
- University of Southern California / Norris Comprehensive Cancer Center
- Cedars-Sinai Medical Center - Samuel Oschin Comprehensive Cancer InstituteRecruiting
- Kaiser Permanente - CARecruiting
- UCSF - Helen Diller Family Comprehensive Cancer Center
- Providence Medical FoundationRecruiting
- Providence St. Joseph HealthRecruiting
- Kaiser Permanente - VallejoRecruiting
- Christiana HospitalRecruiting
- Florida Cancer Specialists - SouthRecruiting
- Miami Cancer InstituteRecruiting
- Florida Cancer Specialists - NorthRecruiting
- Florida Cancer SpecialistsRecruiting
- Moffitt
- Florida Cancer SpecialistsRecruiting
- Maryland Oncology HematologyRecruiting
- Beth Israel Deaconess Medical CenterRecruiting
- Dana Farber Cancer Institute
- Mayo Clinic
- HealthPartners Cancer Research CenterRecruiting
- Washington University School of MedicineRecruiting
- University of North CarolinaRecruiting
- Wake Forest University Health SciencesRecruiting
- The Ohio State University (OSU)Recruiting
- Ohio Health Research InstituteRecruiting
- Penn State Milton S. Hershey Medical CenterRecruiting
- St. Francis Cancer CenterRecruiting
- Sarah Cannon and HCA Research InstituteRecruiting
- The Don & Sybil Harrington Cancer CenterRecruiting
- West Virginia University Cancer InstituteRecruiting
- University of WisconsinRecruiting
- Flinders Medical CentreRecruiting
- Border Medical OncologyRecruiting
- Peninsula and Southeast OncologyRecruiting
- St Vincents Hospital MelbourneRecruiting
- Sir Charles Gairdner HospitalRecruiting
- Calvary Central Districts Hospita
- Lady Davis Institute for Medical Research Jewish General HospitalRecruiting
- Cross Cancer InstituteRecruiting
- McGill University Health Center - Research InstituteRecruiting
- Princess Margaret HospitalRecruiting
- Cancer Care ManitobaRecruiting
- Tampere University HospitalRecruiting
- CHRU de Brest - Hôpital MorvanRecruiting
- CHRU de LilleRecruiting
- Centre Leon BerardRecruiting
- Centre d'Essais Precoces en Cancerologie de MarseilleRecruiting
- Hopital Bichat - Claude Bernard - AP-HPRecruiting
- CHU Rennes - Hopital PontchaillouRecruiting
- Gustave RoussyRecruiting
- Orszagos Koranyi Pulmonologiai IntezetRecruiting
- Szent Borbala KorhazRecruiting
- Torokbalinti TudogyogyintezetRecruiting
- Azienda Ospedaliero-Universitaria delle MarcheRecruiting
- IRCCS Azienda Ospedaliero-Universitaria di Bologna - Policlinico di Sant'OrsolaRecruiting
- Azienda Ospedaliero Universitaria Policlinico G. Rodolico-San Marco - Presidio Ospedaliero G. RodolicoRecruiting
- Istituto Scientifico Romagnolo per lo Studio e la Cura dei TumoriRecruiting
- Istituto Europeo di OncologiaRecruiting
- IRCCS Ospedale San RaffaeleRecruiting
- Istituto Oncologico Veneto-I.R.C.C.S. - Ospedale BusoneraRecruiting
- AOU Citta della Salute e della Scienza di Torino - Ospedale le MolinetteRecruiting
- PanOncology Trials, LLCRecruiting
- Arkhangelsk Clinical Oncological Dispensary
- JSC Group of companies Medsi
- Private Medical Institution Euromedservice
- Saint-Petersburg Clinical Research Center of Specialized Types of Medical Care (Oncology)
- Ogarev Mordovia State University
- JSC Current Medical Technologies
- Volgograd Regional Clinical Oncology Dispensary
- National Cancer Centre SingaporeRecruiting
- Oncocare Cancer CentreRecruiting
- Tan Tock Seng HospitalRecruiting
- Hospital Germans Trias i PujolRecruiting
- Hospital Clinic BarcelonaRecruiting
- Hospital del MarRecruiting
- Institut Catala d'Oncologia - L'HospitaletRecruiting
- Hospital General Universitario Gregorio MaranonRecruiting
- Hospital Universitario 12 de OctubreRecruiting
- Hospital Universitario Puerta de Hierro MajadahondaRecruiting
- Hospital Universitario Ramon y CajalRecruiting
- Hospital Universitario Central de AsturiasRecruiting
- Hospital Universitario Virgen del RocioRecruiting
- Instituto Valenciano de OncologiaRecruiting
- Taichung Veterans General HospitalRecruiting
- Chi-Mei Hospital - Liouying BranchRecruiting
- National Taiwan University HospitalRecruiting
- Linkou Chang Gung Memorial Hospital (CGMHLK)Recruiting
- Imperial College Healthcare NHS Trust
- University College London HospitalRecruiting
- The Christie NHS Foundation TrustRecruiting
- Royal Marsden Hospital - SurreyRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm 7
Arm 8
Arm 9
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
NSCLC Exon 14 Skip Treatment Naive
NSCLC Exon 14 Skip Previously Treated
NSCLC Exon 14 MET Inhibitor Experienced
Basket of tumor types MET amplification except for primary CNS tumors
NSCLC MET amplification and EGFR wild-type
EGFR positive NSCLC MET amplification as an acquired resistance
Basket of solid tumor with MET gene fusions except for primary CNS tumors
Primary CNS tumors with MET alterations
Basket of tumor types wild-type MET with over-expression of HGF and MET
Cohort A-1: APL-101 Oral Capsules
Cohort A-2: APL-101 Oral Capsules
Cohort B: APL-101 Oral Capsules
Cohort C: APL-101 Oral Capsules
Cohort C-1: APL-101 Oral Capsules
Cohort C-2: APL-101 Oral Capsules + Standard of Care EGFR Inhibitor
Cohort D: APL-101 Oral Capsules
Cohort E: APL-101 Oral Capsules
Cohort F: APL-101 Oral Capsules