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Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT03175224
Other study ID # APL-101-01
Secondary ID
Status Recruiting
Phase Phase 2
First received
Last updated
Start date September 27, 2017
Est. completion date November 30, 2026

Study information

Verified date October 2023
Source Apollomics Inc.
Contact Emma (Xiaoning) Cai
Phone 6502094055
Email clinops@apollomicsinc.com
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

To assess: - efficacy of APL-101 as monotherapy for the treatment of NSCLC harboring MET Exon 14 skipping mutations, NSCLC harboring MET amplification, solid tumors harboring MET amplification, solid tumors harboring MET fusion, primary CNS tumors harboring MET alterations, solid tumors harboring wild-type MET with overexpression of HGF and MET - efficacy of APL-101 as an add-on therapy to EGFR inhibitor for the treatment of NSCLC harboring EGFR activating mutations and developed acquired resistance with MET amplification and disease progression after documented CR or PR with 1st line EGFR inhibitors (EGFR-I)


Description:

Phase 1 (lead-in stage of this study) enrollment has been completed. In this Phase 2 study, efficacy, safety, and tolerability will be assessed in the following cohorts: - Cohort A-1: NSCLC EXON 14 skip mutation, previously untreated, MET inhibitor naive (c-Met naïve, 1L) - Cohort A-2: NSCLC EXON 14 skip mutation, previously treated with ≤ 3 prior lines in unresectable or metastatic setting, MET inhibitor naive (c-Met naïve, 2/3L) - Cohort B: NSCLC EXON 14 skip mutation, previously treated with ≤ 3 prior lines in unresectable or metastatic setting, MET inhibitor experienced (c-Met experienced; progressed on prior c-Met inhibitor) - Cohort C: basket of tumor types (e.g., NSCLC, upper gastrointestinal [GI], colorectal, hepatobiliary cancer) harboring MET amplification except for primary CNS tumors, 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 inhibitor naïve - Cohort C-1: NSCLC harboring MET amplification and wild-type epidermal growth factor receptor (EGFR), previously treated; or untreated but refused standard treatment, or if treatment was unavailable or unfeasible (≤ 3 prior lines in unresectable or metastatic setting), MET inhibitor naïve - Cohort C-2: EGFR positive NSCLC harboring MET amplification as an acquired resistance, documented response with first-line EGFR-Inhibitor (PR or CR per RECIST ≥ 12 weeks), radiological documentation of disease progression per RECIST on first-line EGFR inhibitor therapy, MET inhibitor naïve - 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 inhibitor naïve - 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 inhibitor naïve - Cohort F: basket of tumor types harboring wild-type MET with over-expression of HGF and MET (e.g., NSCLC, upper GI, colorectal, hepatobiliary cancer or primary CNS tumors), 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 inhibitor naïve


Recruitment information / eligibility

Status Recruiting
Enrollment 497
Est. completion date November 30, 2026
Est. primary completion date March 30, 2026
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility Major Inclusion Criteria: 1. Men and women 18 years of age or older. 2. 9 cohorts will be enrolled: - Cohort A1 / Exon 14 NSCLC MET inhibitor naive in first line: Histologically or cytologically confirmed NSCLC with Exon 14 skipping mutations; all histologies; unresectable or metastatic disease (Stage 3b/4); treatment-naive subjects in first line; not received any MET inhibitor and no known MET kinase inhibitor resistance mutations - Cohort A2 / Exon 14 NSCLC - MET inhibitor naïve: Histologically or cytologically confirmed NSCLC with Exon 14 skipping mutations; all histologies; unresectable or metastatic disease (Stage 3b/4); pretreated subjects refractory to or intolerant of standard therapies with no more than three lines of prior therapy in the unresectable or metastatic setting; not received any MET inhibitor 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, with MET amplification; unresectable or metastatic disease, refractory to or intolerant of standard therapies, or refused standard therapies, or if therapy was unavailable or unfeasible, with no more than 3 prior lines of therapy in the unresectable or metastatic setting; not received any MET inhibitor and no known MET kinase inhibitor resistance mutations - Cohort C1 / MET amplification and wild-type EGFR NSCLC: NSCLC regardless of histology, harboring MET amplification and wild-type EGFR; unresectable or metastatic disease, previously untreated or treated with no more than 3 prior lines of therapy in the unresectable or metastatic setting; not received any MET inhibitor and no known MET kinase inhibitor resistance mutations - Cohort C2 / EGFR positive NSCLC with acquired MET amplification (APL-101 Add-on Therapy): Unresectable or metastatic NSCLC regardless of histology, harboring EGFR activating mutations with acquired MET-Amplification as resistance mechanism to the EGFR-I; developed resistance to first-line EGFR-inhibitor therapy after an initial response (documented PR for at least 12 weeks); radiological documentation of disease progression per RECIST on first-line EGFR inhibitor therapy; currently on an EGFR-inhibitor therapy and agrees to receive APL-101 as an add-on therapy during the study; no history of interstitial lung disease (ILD)/pneumonitis, Grade =3 liver toxicity or QT prolongation with EGFR-I therapy; not received any MET inhibitor and no known MET kinase inhibitor resistance mutations - Cohort D / MET fusion basket tumor types excluding primary CNS tumors: any solid tumor type regardless of histology excluding primary CNS tumors; unresectable or metastatic disease, refractory to or intolerant of standard therapies, or refused standard therapies, or if therapy was unavailable or unfeasible, with no more than 3 prior lines of therapy in the unresectable or metastatic setting; not received any MET inhibitor and no known MET kinase inhibitor resistance mutations - Cohort E / Primary CNS tumors with MET alterations: subjects with primary CNS tumors who meet inclusion criteria of MET dysregulations defined as single or co-occurred MET fusion including PTPRZ1-MET (ZM) fusion, MET Exon 14 skipping mutations, or MET amplification; refractory to or intolerant of standard therapies, or refused standard therapies, or if therapy was unavailable or unfeasible, with no more than 3 prior lines of therapy in the unresectable or metastatic setting; not received any MET inhibitor and no known MET kinase inhibitor resistance mutations; neurological symptoms controlled on a stable/decreasing dose of steroids for at least 2 weeks before C1D1 - Cohort F / Basket tumor types harboring wild-type MET with over-expression of HGF and MET: any solid tumor type regardless of histology harboring wild-type MET with overexpression of HGF and MET; Unresectable or metastatic disease, refractory to or intolerant of standard therapies, or refused standard therapies, or if therapy was unavailable or unfeasible, with no more than 3 prior lines of therapy in the unresectable or metastatic setting; not received any MET inhibitor and no known MET kinase inhibitor resistance mutations 3. Treated or untreated asymptomatic parenchymal CNS disease or leptomeningeal disease is allowed. 4. Presence of =1 measurable lesion (scan done =28 days of C1D1) to serve as target lesion according to relevant criteria 5. ECOG performance status of 0-1. For subjects with primary CNS tumors, KPS score =70. 6. Acceptable organ function 7. For all prior anticancer treatment, a duration of 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. 8. Adequate cardiac function 9. Women of child-bearing potential must have a negative serum or Beta-hCG at screening or evidence of surgical sterility or evidence of post-menopausal status 10. No planned major surgery within 4 weeks of first dose of APL-101 11. Expected survival (life expectancy) = 3 months from C1D1 12. Provision of sample; e.g. archival or a fresh tumor biopsy sample (if safe and feasible) either from the primary or a metastatic site) or liquid biopsy sample (if tumor tissue is insufficient or lacking, and approved by the sponsor) is required for prospective central lab confirmation for study entry (subjects with previously confirmed molecular status by the Sponsor designated central lab or FDA approved NGS based MET testing may be exempted, subjected to Sponsor approval. Major Exclusion Criteria: 1. Hypersensitivity to APL-101, excipients of the drug product, or other components of the study treatment regimen. 2. Known actionable mutation/gene rearrangement of EGFR (except for NSCLC subjects in Cohort C and C-2), ALK, ROS1, RET, NTRK, KRAS, and BRAF. 3. Use or intended use of any other investigational product, including herbal medications, through Study Treatment Termination. 4. Active uncontrolled systemic bacterial, viral, or fungal infection or clinically significant, active disease process, which in the opinion of the investigator makes the risk: benefit unfavorable for the participation of the trial. 5. Life-threatening illness, significant organ system dysfunction or comorbid conditions, or other reasons that, in the investigator's opinion, could compromise the subject's safety or the integrity of the study outcomes, or interfere with the absorption or metabolism of APL-101. 6. 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, or concurrent treatment with a medication that is a known risk for prolonging the QT interval. Chronic controlled atrial fibrillation is not excluded. 7. Historical seropositive results consistent with active infection for hepatitis C virus (HCV) or hepatitis B virus (HBV) with high viral loads not actively managed with antiviral therapy and human immunodeficiency virus (HIV) positive subjects who are not clinically stable or controlled on their medication (asymptomatic subjects with CD4+ T-cell (CD4+) counts = 350 cells/µL and have not had an opportunistic infection within the past 12 months prior to first dose of APL-101 would be eligible for study entry. If history is unclear, relevant test(s) at Screening will be required to confirm eligibility. 8. Known significant mental illness or other conditions such as active alcohol or other substance abuse that, in the opinion of the investigator, predisposes the subject to high risk of noncompliance with the protocol treatment or assessments. 9. Unable to swallow orally administered medication whole. 10. Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter drug absorption 11. Women who are breastfeeding 12. History of another malignancy within 3 years prior to C1D1. A subject with the following malignancies is allowed if considered cured or unlikely to recur within 3 years: 1. Carcinoma of the skin without melanomatous features. 2. Curatively treated cervical carcinoma in situ. 3. Bladder tumors considered superficial such as noninvasive (T1a) and carcinoma in situ (T1s), thyroid papillary cancer with prior treatment, prostate cancer which has been surgically or medically treated and not likely to recur within 3 years. 13. Subjects who are unable or unwilling to discontinue excluded medications (drugs with known QTc risk and known strong cytochrome P450 [CYP]3A4 inducer and/or strong inhibitors) for at least 5 half-lives prior to first dose of study drug. Subjects may qualify if such medication(s) can be safely replaced with alternate medications with less risk of drug-drug interaction. 14. Subjects with active COVID-19 infection. 15. 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.

Study Design


Intervention

Drug:
APL-101 Oral Capsules
Subjects will receive APL-101 capsules BID for oral administration.

Locations

Country Name City State
Australia Border Medical Oncology Albury
Australia Flinders Medical Centre Bedford Park South Australia
Australia Peninsula and Southeast Oncology Frankston
Australia St Vincents Hospital Melbourne Melbourne
Australia Sir Charles Gairdner Hospital Nedlands
Australia Calvary Central Districts Hospita North Adelaide
Canada Cross Cancer Institute Edmonton
Canada Lady Davis Institute for Medical Research Jewish General Hospital Montreal Quebec
Canada McGill University Health Center - Research Institute Montréal
Canada Princess Margaret Hospital Toronto
Canada Cancer Care Manitoba Winnipeg
Finland Tampere University Hospital Tampere
France CHRU de Brest - Hôpital Morvan Brest
France CHRU de Lille Lille
France Centre Leon Berard Lyon
France Centre d'Essais Precoces en Cancerologie de Marseille Marseille
France Hopital Bichat - Claude Bernard - AP-HP Paris
France CHU Rennes - Hopital Pontchaillou Rennes
France Gustave Roussy Villejuif
Hungary Orszagos Koranyi Pulmonologiai Intezet Budapest
Hungary Szent Borbala Korhaz Tatabanya
Hungary Torokbalinti Tudogyogyintezet Torokbalint
Italy Azienda Ospedaliero-Universitaria delle Marche Ancona
Italy IRCCS Azienda Ospedaliero-Universitaria di Bologna - Policlinico di Sant'Orsola Bologna
Italy Azienda Ospedaliero Universitaria Policlinico G. Rodolico-San Marco - Presidio Ospedaliero G. Rodolico Catania
Italy Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori Meldola
Italy IRCCS Ospedale San Raffaele Milan
Italy Istituto Europeo di Oncologia Milano
Italy Istituto Oncologico Veneto-I.R.C.C.S. - Ospedale Busonera Padova
Italy AOU Citta della Salute e della Scienza di Torino - Ospedale le Molinette Torino
Puerto Rico PanOncology Trials, LLC Rio Piedras
Russian Federation Arkhangelsk Clinical Oncological Dispensary Arkhangelsk
Russian Federation JSC Group of companies Medsi Otradnoye
Russian Federation Private Medical Institution Euromedservice Saint Petersburg
Russian Federation Saint-Petersburg Clinical Research Center of Specialized Types of Medical Care (Oncology) Saint Petersburg
Russian Federation Ogarev Mordovia State University Saransk
Russian Federation JSC Current Medical Technologies St. Petersburg
Russian Federation Volgograd Regional Clinical Oncology Dispensary Volgograd
Singapore National Cancer Centre Singapore Singapore
Singapore Oncocare Cancer Centre Singapore
Singapore Tan Tock Seng Hospital Singapore
Spain Hospital Germans Trias i Pujol Badalona
Spain Hospital Clinic Barcelona Barcelona
Spain Hospital del Mar Barcelona
Spain Institut Catala d'Oncologia - L'Hospitalet Barcelona
Spain Hospital General Universitario Gregorio Maranon Madrid
Spain Hospital Universitario 12 de Octubre Madrid
Spain Hospital Universitario Puerta de Hierro Majadahonda Madrid
Spain Hospital Universitario Ramon y Cajal Madrid
Spain Hospital Universitario Central de Asturias Oviedo
Spain Hospital Universitario Virgen del Rocio Sevilla
Spain Instituto Valenciano de Oncologia Valencia
Taiwan Taichung Veterans General Hospital Taichung
Taiwan Chi-Mei Hospital - Liouying Branch Tainan
Taiwan National Taiwan University Hospital Taipei City
Taiwan Linkou Chang Gung Memorial Hospital (CGMHLK) Taoyuan City
United Kingdom Imperial College Healthcare NHS Trust London
United Kingdom University College London Hospital London
United Kingdom The Christie NHS Foundation Trust Manchester
United Kingdom Royal Marsden Hospital - Surrey Surrey Quays
United States The Don & Sybil Harrington Cancer Center Amarillo Texas
United States Beth Israel Deaconess Medical Center Boston Massachusetts
United States Dana Farber Cancer Institute Boston Massachusetts
United States University of North Carolina Chapel Hill North Carolina
United States Ohio Health Research Institute Columbus Ohio
United States The Ohio State University (OSU) Columbus Ohio
United States Florida Cancer Specialists - South Fort Myers Florida
United States St. Francis Cancer Center Greenville South Carolina
United States Penn State Milton S. Hershey Medical Center Hershey Pennsylvania
United States Loma Linda University Medical Center Loma Linda California
United States Cedars-Sinai Medical Center - Samuel Oschin Comprehensive Cancer Institute Los Angeles California
United States University of Southern California / Norris Comprehensive Cancer Center Los Angeles California
United States University of Wisconsin Madison Wisconsin
United States Miami Cancer Institute Miami Florida
United States West Virginia University Cancer Institute Morgantown West Virginia
United States Sarah Cannon and HCA Research Institute Nashville Tennessee
United States Christiana Hospital Newark Delaware
United States Kaiser Permanente - CA Riverside California
United States Mayo Clinic Rochester Minnesota
United States Washington University School of Medicine Saint Louis Missouri
United States HealthPartners Cancer Research Center Saint Louis Park Minnesota
United States Florida Cancer Specialists - North Saint Petersburg Florida
United States UCSF - Helen Diller Family Comprehensive Cancer Center San Francisco California
United States Providence Medical Foundation Santa Monica California
United States Providence St. Joseph Health Santa Rosa California
United States Maryland Oncology Hematology Silver Spring Maryland
United States Florida Cancer Specialists Tallahassee Florida
United States Moffitt Tampa Florida
United States Kaiser Permanente - Vallejo Vallejo California
United States Florida Cancer Specialists West Palm Beach Florida
United States Wake Forest University Health Sciences Winston-Salem North Carolina

Sponsors (1)

Lead Sponsor Collaborator
Apollomics Inc.

Countries where clinical trial is conducted

United States,  Australia,  Canada,  Finland,  France,  Hungary,  Italy,  Puerto Rico,  Russian Federation,  Singapore,  Spain,  Taiwan,  United Kingdom, 

Outcome

Type Measure Description Time frame Safety issue
Primary Objective response rate (ORR = CR + PR) per IRC committee (BIRC) based on RECIST v1.1 (or relevant criteria per tumor type) Anti-tumor activity per RECIST v1.1, RANO criteria for CNS tumors, or relevant evaluation criteria per tumor type. From time of informed consent signature through completion of treatment (1 cycle = 28 days) or progression
Secondary Median duration of response (DOR) per IRC. DOR per RECIST v1.1 criteria, RANO criteria for CNS tumors, or relevant evaluation criteria per tumor type. Approximately 2 years
Secondary ORR per investigator assessment based on RECIST v1.1. ORR per RECIST v1.1 or relevant evaluation criteria per tumor type. Approximately 2 years
Secondary Median DOR per investigator assessment. DOR per RECIST v1.1, RANO criteria for CNS tumors, or relevant evaluation criteria per tumor type. Approximately 2 years
Secondary Antitumor activity by clinical benefit rate (CR + PR + SD = 4 cycles) based on RECIST v1.1, RANO criteria for CNS tumors, or other relevant criteria per tumor type Median time to progression (TTP). Benefit rate per RECIST v1.1, RANO criteria for CNS tumors, or relevant evaluation criteria per tumor type. Approximately 2 years
Secondary Median time to progression (TTP). TTP per RECIST v1.1 or relevant evaluation criteria per tumor type. Approximately 2 years
Secondary Progression Free Survival (PFS) and overall survival (OS) at 6, 12, 18 and 24 months PFS and OS per RECIST v1.1 or relevant evaluation criteria per tumor type. Approximately 3 years
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