Phase
Condition
Thyroid Cancer
Gastric Cancer
Pancreatic Cancer
Treatment
APL-101 Oral Capsules
Clinical Study ID
Ages > 18 All Genders
Study Summary
Eligibility Criteria
Inclusion
Major Inclusion Criteria:
Men and women 18 years of age or older.
9 cohorts will be enrolled:
Cohort A1 / Exon 14 NSCLC MET inhibitor naive in first line: Histologically orcytologically confirmed NSCLC with Exon 14 skipping mutations; all histologies;unresectable or metastatic disease (Stage 3b/4); treatment-naive subjects infirst line; not received any MET inhibitor and no known MET kinase inhibitorresistance mutations
Cohort A2 / Exon 14 NSCLC - MET inhibitor naïve: Histologically orcytologically confirmed NSCLC with Exon 14 skipping mutations; all histologies;unresectable or metastatic disease (Stage 3b/4); pretreated subjects refractoryto or intolerant of standard therapies with no more than three lines of priortherapy in the unresectable or metastatic setting; not received any METinhibitor and no known MET kinase inhibitor resistance mutations
Cohort B / Exon 14 NSCLC MET inhibitor experienced: ENROLLMENT COMPLETED
Cohort C / MET amplification basket tumor types excluding primary CNS tumors:Any solid tumor type regardless of histology excluding primary CNS tumors, withMET amplification; unresectable or metastatic disease, refractory to orintolerant of standard therapies, or refused standard therapies, or if therapywas unavailable or unfeasible, with no more than 3 prior lines of therapy inthe unresectable or metastatic setting; not received any MET inhibitor and noknown MET kinase inhibitor resistance mutations
Cohort C1 / MET amplification and wild-type EGFR NSCLC: NSCLC regardless ofhistology, harboring MET amplification and wild-type EGFR; unresectable ormetastatic disease, previously untreated or treated with no more than 3 priorlines of therapy in the unresectable or metastatic setting; not received anyMET inhibitor and no known MET kinase inhibitor resistance mutations
Cohort C2 / EGFR positive NSCLC with acquired MET amplification (APL-101 Add-onTherapy): Unresectable or metastatic NSCLC regardless of histology, harboringEGFR activating mutations with acquired MET-Amplification as resistancemechanism to the EGFR-I; developed resistance to first-line EGFR-inhibitortherapy after an initial response (documented PR for at least 12 weeks);radiological documentation of disease progression per RECIST on first-line EGFRinhibitor therapy; currently on an EGFR-inhibitor therapy and agrees to receiveAPL-101 as an add-on therapy during the study; no history of interstitial lungdisease (ILD)/pneumonitis, Grade ≥3 liver toxicity or QT prolongation withEGFR-I therapy; not received any MET inhibitor and no known MET kinaseinhibitor resistance mutations
Cohort D / MET fusion basket tumor types excluding primary CNS tumors: anysolid tumor type regardless of histology excluding primary CNS tumors;unresectable or metastatic disease, refractory to or intolerant of standardtherapies, or refused standard therapies, or if therapy was unavailable orunfeasible, with no more than 3 prior lines of therapy in the unresectable ormetastatic setting; not received any MET inhibitor and no known MET kinaseinhibitor resistance mutations
Cohort E / Primary CNS tumors with MET alterations: subjects with primary CNStumors who meet inclusion criteria of MET dysregulations defined as single orco-occurred MET fusion including PTPRZ1-MET (ZM) fusion, MET Exon 14 skippingmutations, or MET amplification; refractory to or intolerant of standardtherapies, or refused standard therapies, or if therapy was unavailable orunfeasible, with no more than 3 prior lines of therapy in the unresectable ormetastatic setting; not received any MET inhibitor and no known MET kinaseinhibitor resistance mutations; neurological symptoms controlled on astable/decreasing dose of steroids for at least 2 weeks before C1D1
Cohort F / Basket tumor types harboring wild-type MET with over-expression ofHGF and MET: any solid tumor type regardless of histology harboring wild-typeMET with overexpression of HGF and MET; Unresectable or metastatic disease,refractory to or intolerant of standard therapies, or refused standardtherapies, or if therapy was unavailable or unfeasible, with no more than 3prior lines of therapy in the unresectable or metastatic setting; not receivedany MET inhibitor and no known MET kinase inhibitor resistance mutations
Treated or untreated asymptomatic parenchymal CNS disease or leptomeningeal diseaseis allowed.
Presence of ≥1 measurable lesion (scan done ≤28 days of C1D1) to serve as targetlesion according to relevant criteria
ECOG performance status of 0-1. For subjects with primary CNS tumors, KPS score ≥70.
Acceptable organ function
For all prior anticancer treatment, a duration of 30 days or 5 half-lives of theagents used, whichever is shorter, must have elapsed, and any encountered toxicitymust have resolved to levels meeting all the other eligibility criteria prior to thefirst dose of study treatment. Palliative radiotherapy to non-target lesions shouldbe completed within 2 weeks prior to APL-101 administration.
Adequate cardiac function
Women of child-bearing potential must have a negative serum or Beta-hCG at screeningor evidence of surgical sterility or evidence of post-menopausal status
No planned major surgery within 4 weeks of first dose of APL-101
Expected survival (life expectancy) ≥ 3 months from C1D1
Provision of sample; e.g. archival or a fresh tumor biopsy sample (if safe andfeasible) either from the primary or a metastatic site) or liquid biopsy sample (iftumor tissue is insufficient or lacking, and approved by the sponsor) is requiredfor prospective central lab confirmation for study entry (subjects with previouslyconfirmed molecular status by the Sponsor designated central lab or FDA approved NGSbased MET testing may be exempted, subjected to Sponsor approval.
Exclusion
Major Exclusion Criteria:
Hypersensitivity to APL-101, excipients of the drug product, or other components ofthe study treatment regimen.
Known actionable mutation/gene rearrangement of EGFR (except for NSCLC subjects inCohort C and C-2), ALK, ROS1, RET, NTRK, KRAS, and BRAF.
Use or intended use of any other investigational product, including herbalmedications, through Study Treatment Termination.
Active uncontrolled systemic bacterial, viral, or fungal infection or clinicallysignificant, active disease process, which in the opinion of the investigator makesthe risk: benefit unfavorable for the participation of the trial.
Life-threatening illness, significant organ system dysfunction or comorbidconditions, or other reasons that, in the investigator's opinion, could compromisethe subject's safety or the integrity of the study outcomes, or interfere with theabsorption or metabolism of APL-101.
Unstable angina or myocardial infarction within 1 year prior to first dose ofAPL-101, symptomatic or unstable arrhythmia requiring medical therapy, history ofcongenital prolonged QT syndrome, prolonged QT interval corrected by Fridericiaformula (QTcF) at screening, or concurrent treatment with a medication that is aknown risk for prolonging the QT interval. Chronic controlled atrial fibrillation isnot excluded.
Historical seropositive results consistent with active infection for hepatitis Cvirus (HCV) or hepatitis B virus (HBV) with high viral loads not actively managedwith antiviral therapy and human immunodeficiency virus (HIV) positive subjects whoare not clinically stable or controlled on their medication (asymptomatic subjectswith CD4+ T-cell (CD4+) counts ≥ 350 cells/μL and have not had an opportunisticinfection within the past 12 months prior to first dose of APL-101 would be eligiblefor study entry. If history is unclear, relevant test(s) at Screening will berequired to confirm eligibility.
Known significant mental illness or other conditions such as active alcohol or othersubstance abuse that, in the opinion of the investigator, predisposes the subject tohigh risk of noncompliance with the protocol treatment or assessments.
Unable to swallow orally administered medication whole.
Impairment of gastrointestinal function or gastrointestinal disease that maysignificantly alter drug absorption
Women who are breastfeeding
History of another malignancy within 3 years prior to C1D1. A subject with thefollowing malignancies is allowed if considered cured or unlikely to recur within 3years:
Carcinoma of the skin without melanomatous features.
Curatively treated cervical carcinoma in situ.
Bladder tumors considered superficial such as noninvasive (T1a) and carcinomain situ (T1s), thyroid papillary cancer with prior treatment, prostate cancerwhich has been surgically or medically treated and not likely to recur within 3years.
Subjects who are unable or unwilling to discontinue excluded medications (drugs withknown QTc risk and known strong cytochrome P450 [CYP]3A4 inducer and/or stronginhibitors) for at least 5 half-lives prior to first dose of study drug. Subjectsmay qualify if such medication(s) can be safely replaced with alternate medicationswith less risk of drug-drug interaction.
Subjects with active COVID-19 infection.
Symptomatic and/or neurologically unstable CNS metastases, or who require anincrease in steroid dose to control CNS disease. Subjects who have been receiving astable steroid dose for at least 2 weeks prior to C1D1 may be allowed.
Study Design
Study Description
Connect with a study center
Flinders Medical Centre
Bedford Park, South Australia
AustraliaSite Not Available
Border Medical Oncology
Albury,
AustraliaSite Not Available
Peninsula and Southeast Oncology
Frankston,
AustraliaSite Not Available
St Vincents Hospital Melbourne
Melbourne,
AustraliaActive - Recruiting
Sir Charles Gairdner Hospital
Nedlands,
AustraliaSite Not Available
Calvary Central Districts Hospita
North Adelaide,
AustraliaSite Not Available
Lady Davis Institute for Medical Research Jewish General Hospital
Montreal, Quebec
CanadaSite Not Available
Cross Cancer Institute
Edmonton,
CanadaActive - Recruiting
McGill University Health Center - Research Institute
Montréal,
CanadaActive - Recruiting
Princess Margaret Hospital
Toronto,
CanadaActive - Recruiting
Cancer Care Manitoba
Winnipeg,
CanadaActive - Recruiting
Helsinki University Central Hospita
Helsinki,
FinlandSite Not Available
Tampere University Hospital
Tampere,
FinlandSite Not Available
CHRU de Brest - Hôpital Morvan
Brest,
FranceActive - Recruiting
CHRU de Lille
Lille,
FranceSite Not Available
Centre Leon Berard
Lyon,
FranceActive - Recruiting
Centre d'Essais Precoces en Cancerologie de Marseille
Marseille,
FranceActive - Recruiting
Hopital Bichat - Claude Bernard - AP-HP
Paris,
FranceActive - Recruiting
CHU Rennes - Hopital Pontchaillou
Rennes,
FranceSite Not Available
Gustave Roussy
Villejuif,
FranceActive - Recruiting
Hong Kong United Oncology Centre
Hong Kong,
Hong KongSite Not Available
Orszagos Koranyi Pulmonologiai Intezet
Budapest,
HungaryActive - Recruiting
Komarom-Esztergom Varmegyei Szent Borbala Korhaz
Tatabanya,
HungaryActive - Recruiting
Szent Borbala Korhaz
Tatabanya,
HungaryActive - Recruiting
Torokbalinti Tudogyogyintezet
Torokbalint,
HungarySite Not Available
Azienda Ospedaliero-Universitaria delle Marche
Ancona, 60126
ItalySite Not Available
IRCCS Azienda Ospedaliero-Universitaria di Bologna - Policlinico di Sant'Orsola
Bologna,
ItalyActive - Recruiting
Azienda Ospedaliero Universitaria Policlinico G. Rodolico-San Marco - Presidio Ospedaliero G. Rodolico
Catania,
ItalySite Not Available
Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori
Meldola,
ItalyActive - Recruiting
IRCCS Ospedale San Raffaele
Milan,
ItalyActive - Recruiting
Istituto Europeo di Oncologia
Milano,
ItalyActive - Recruiting
Istituto Oncologico Veneto-I.R.C.C.S. - Ospedale Busonera
Padova,
ItalyActive - Recruiting
AOU Citta della Salute e della Scienza di Torino - Ospedale le Molinette
Torino,
ItalySite Not Available
PanOncology Trials, LLC
Rio Piedras,
Puerto RicoSite Not Available
Arkhangelsk Clinical Oncological Dispensary
Arkhangelsk,
Russian FederationSite Not Available
JSC Group of companies Medsi
Otradnoye,
Russian FederationSite Not Available
Private Medical Institution Euromedservice
Saint Petersburg,
Russian FederationSite Not Available
Saint-Petersburg Clinical Research Center of Specialized Types of Medical Care (Oncology)
Saint Petersburg,
Russian FederationSite Not Available
Ogarev Mordovia State University
Saransk,
Russian FederationSite Not Available
JSC Current Medical Technologies
St. Petersburg,
Russian FederationSite Not Available
Volgograd Regional Clinical Oncology Dispensary
Volgograd,
Russian FederationSite Not Available
National Cancer Centre Singapore
Singapore,
SingaporeActive - Recruiting
Oncocare Cancer Centre
Singapore,
SingaporeActive - Recruiting
Tan Tock Seng Hospital
Singapore,
SingaporeActive - Recruiting
Hospital Germans Trias i Pujol
Badalona,
SpainActive - Recruiting
Hospital Clinic Barcelona
Barcelona,
SpainActive - Recruiting
Hospital del Mar
Barcelona,
SpainActive - Recruiting
Institut Catala d'Oncologia - L'Hospitalet
Barcelona,
SpainActive - Recruiting
Hospital General Universitario Gregorio Maranon
Madrid,
SpainActive - Recruiting
Hospital Universitario 12 de Octubre
Madrid,
SpainActive - Recruiting
Hospital Universitario Puerta de Hierro Majadahonda
Madrid,
SpainActive - Recruiting
Hospital Universitario Ramon y Cajal
Madrid,
SpainActive - Recruiting
Hospital Universitario Puerta de Hierro Majadahonda
Majadahonda,
SpainSite Not Available
Hospital Universitario Central de Asturias
Oviedo,
SpainSite Not Available
Hospital Universitario Donostia
San Sebastián,
SpainSite Not Available
Hospital Universitario Virgen del Rocio
Sevilla,
SpainSite Not Available
Instituto Valenciano de Oncologia
Valencia,
SpainActive - Recruiting
Taipei Medical University - Shuang Ho Hospital
New Taipei City,
TaiwanSite Not Available
Taichung Veterans General Hospital
Taichung,
TaiwanSite Not Available
Chi-Mei Hospital - Liouying Branch
Tainan,
TaiwanSite Not Available
Taipei Medical University Hospital
Taipei,
TaiwanSite Not Available
National Taiwan University Hospital
Taipei City,
TaiwanActive - Recruiting
Linkou Chang Gung Memorial Hospital (CGMHLK)
Taoyuan City,
TaiwanSite Not Available
City Hematology Center of Municipal Non-Profit Enterprise "City Clinical Hospital #4" DCC
Dnipropetrovs'k,
UkraineSite Not Available
Communal Non-commercial Enterprise of Kharkiv Regional Council Regional Clinical Specialized Dispensary of Radiation Protection of Population, Department of Surger
Kharkiv,
UkraineSite Not Available
State Institution V.T.Zaitsev Institute of General and Urgent Surgery of National Academy of Medical Sciences of Ukraine, Department of Purulent Surgery
Kharkiv,
UkraineSite Not Available
Kyiv Municipal Clinical Oncology Center
Kyiv,
UkraineSite Not Available
Imperial College Healthcare NHS Trust
London,
United KingdomSite Not Available
University College London Hospital
London,
United KingdomActive - Recruiting
The Christie NHS Foundation Trust
Manchester,
United KingdomActive - Recruiting
Royal Marsden Hospital - Surrey
Surrey Quays,
United KingdomActive - Recruiting
Banner MD Anderson
Gilbert, Arizona 85234
United StatesSite Not Available
Mayo Clinic
Phoenix, Arizona 85054
United StatesSite Not Available
Kaiser Permanente - CA
Escondido, California 92025
United StatesSite Not Available
Loma Linda University Medical Center
Loma Linda, California 92354
United StatesSite Not Available
Cedars-Sinai Medical Center - Samuel Oschin Comprehensive Cancer Institute
Los Angeles, California 90048
United StatesActive - Recruiting
University of California, Los Angeles (UCLA) Ronald Reagan Medical Center
Los Angeles, California 90095
United StatesActive - Recruiting
University of Southern California / Norris Comprehensive Cancer Center
Los Angeles, California 90033
United StatesSite Not Available
Kaiser Permanente - CA
Riverside, California 92505
United StatesSite Not Available
UCSF - Helen Diller Family Comprehensive Cancer Center
San Francisco, California 94158
United StatesSite Not Available
Univeristy of California San Francisco
San Francisco, California 94115
United StatesSite Not Available
Providence Medical Foundation
Santa Monica, California 90404
United StatesSite Not Available
Providence St. Joseph Health
Santa Rosa, California 95403
United StatesSite Not Available
St. Joseph Health
Santa Rosa, California 95403
United StatesActive - Recruiting
Kaiser Permanente - Vallejo
Vallejo, California 94589
United StatesSite Not Available
Christiana Hospital
Newark, Delaware 19713
United StatesSite Not Available
Florida Cancer Specialists - South
Fort Myers, Florida 33908
United StatesSite Not Available
Mayo Clinic
Jacksonville, Florida 32224
United StatesSite Not Available
Miami Cancer Institute
Miami, Florida 33176
United StatesSite Not Available
Florida Hospital Cancer Institute
Orlando, Florida 32803
United StatesSite Not Available
Florida Cancer Specialists - North
Saint Petersburg, Florida 33705
United StatesActive - Recruiting
Florida Cancer Specialists
Tallahassee, Florida 32308
United StatesSite Not Available
Moffitt
Tampa, Florida 33612
United StatesSite Not Available
Florida Cancer Specialists
West Palm Beach, Florida 33401
United StatesSite Not Available
Ochsner Clinic Foundation
New Orleans, Louisiana 70121
United StatesSite Not Available
Maryland Oncology Hematology
Silver Spring, Maryland 20904
United StatesSite Not Available
Beth Israel Deaconess Medical Center
Boston, Massachusetts 02215
United StatesActive - Recruiting
Dana Farber Cancer Institute
Boston, Massachusetts 02215
United StatesSite Not Available
Mayo Clinic
Rochester, Minnesota 55905
United StatesSite Not Available
HealthPartners Cancer Research Center
Saint Louis Park, Minnesota 55416
United StatesSite Not Available
Park Nicollet Institute - Frauenshuh Cancer Center
Saint Louis Park, Minnesota 55416
United StatesActive - Recruiting
HCA Midwest Health
Kansas City, Missouri 66211
United StatesSite Not Available
Washington University School of Medicine
Saint Louis, Missouri 63110
United StatesSite Not Available
University of North Carolina
Chapel Hill, North Carolina 27599
United StatesActive - Recruiting
Wake Forest University Health Sciences
Winston-Salem, North Carolina 27157
United StatesSite Not Available
Cleveland Clinic
Cleveland, Ohio 44195
United StatesSite Not Available
Ohio Health Research Institute
Columbus, Ohio 43214
United StatesSite Not Available
The Ohio State University (OSU)
Columbus, Ohio 43210
United StatesActive - Recruiting
Kettering Health Network
Kettering, Ohio 45429
United StatesSite Not Available
Penn State Milton S. Hershey Medical Center
Hershey, Pennsylvania 17033
United StatesActive - Recruiting
St. Francis Cancer Center
Greenville, South Carolina 29607
United StatesSite Not Available
Sarah Cannon and HCA Research Institute
Nashville, Tennessee 37203
United StatesSite Not Available
The Don & Sybil Harrington Cancer Center
Amarillo, Texas 79106
United StatesSite Not Available
Huntsman cancer Institute
Salt Lake City, Utah 84112
United StatesSite Not Available
MultiCare Health System
Tacoma, Washington 98405
United StatesSite Not Available
West Virginia University Cancer Institute
Morgantown, West Virginia 26506
United StatesSite Not Available
University of Wisconsin
Madison, Wisconsin 53792
United StatesActive - Recruiting
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