Lung Cancer Clinical Trial

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

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

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Full 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

View Eligibility Criteria

Eligibility Criteria

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 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
Treated or untreated asymptomatic parenchymal CNS disease or leptomeningeal disease is allowed.
Presence of ≥1 measurable lesion (scan done ≤28 days of C1D1) to serve as target lesion 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 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.
Adequate cardiac function
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
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 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:

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 NSCLC subjects in Cohort C and C-2), ALK, ROS1, RET, NTRK, KRAS, and BRAF.
Use or intended use of any other investigational product, including herbal medications, through Study Treatment Termination.
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.
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.
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.
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.
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.
Unable to swallow orally administered medication whole.
Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter drug absorption
Women who are breastfeeding

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:

Carcinoma of the skin without melanomatous features.
Curatively treated cervical carcinoma in situ.
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.
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.
Subjects with active COVID-19 infection.
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 is for people with:

Lung Cancer

Phase:

Phase 2

Estimated Enrollment:

497

Study ID:

NCT03175224

Recruitment Status:

Recruiting

Sponsor:

Apollomics Inc.

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There are 31 Locations for this study

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Loma Linda University Medical Center
Loma Linda California, 92354, United States
University of Southern California / Norris Comprehensive Cancer Center
Los Angeles California, 90033, United States
Cedars-Sinai Medical Center - Samuel Oschin Comprehensive Cancer Institute
Los Angeles California, 90048, United States
Kaiser Permanente - CA
Riverside California, 92505, United States
UCSF - Helen Diller Family Comprehensive Cancer Center
San Francisco California, 94158, United States
Providence Medical Foundation
Santa Monica California, 90404, United States
Providence St. Joseph Health
Santa Rosa California, 95403, United States
Kaiser Permanente - Vallejo
Vallejo California, 94589, United States
Christiana Hospital
Newark Delaware, 19713, United States
Florida Cancer Specialists - South
Fort Myers Florida, 33908, United States
Miami Cancer Institute
Miami Florida, 33176, United States
Florida Cancer Specialists - North
Saint Petersburg Florida, 33705, United States
Florida Cancer Specialists
Tallahassee Florida, 32308, United States
Moffitt
Tampa Florida, 33612, United States
Florida Cancer Specialists
West Palm Beach Florida, 33401, United States
Maryland Oncology Hematology
Silver Spring Maryland, 20904, United States
Beth Israel Deaconess Medical Center
Boston Massachusetts, 02215, United States
Dana Farber Cancer Institute
Boston Massachusetts, 02215, United States
Mayo Clinic
Rochester Minnesota, 55905, United States
HealthPartners Cancer Research Center
Saint Louis Park Minnesota, 55416, United States
Washington University School of Medicine
Saint Louis Missouri, 63110, United States
University of North Carolina
Chapel Hill North Carolina, 27599, United States
Wake Forest University Health Sciences
Winston-Salem North Carolina, 27157, United States
The Ohio State University (OSU)
Columbus Ohio, 43210, United States
Ohio Health Research Institute
Columbus Ohio, 43214, United States
Penn State Milton S. Hershey Medical Center
Hershey Pennsylvania, 17033, United States
St. Francis Cancer Center
Greenville South Carolina, 29607, United States
Sarah Cannon and HCA Research Institute
Nashville Tennessee, 37203, United States
The Don & Sybil Harrington Cancer Center
Amarillo Texas, 79106, United States
West Virginia University Cancer Institute
Morgantown West Virginia, 26506, United States More Info
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University of Wisconsin
Madison Wisconsin, 53792, United States
Flinders Medical Centre
Bedford Park South Australia, , Australia
Border Medical Oncology
Albury , , 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 , , Australia
Lady Davis Institute for Medical Research Jewish General Hospital
Montreal Quebec, , Canada
Cross Cancer Institute
Edmonton , , Canada
McGill University Health Center - Research Institute
Montréal , , Canada
Princess Margaret Hospital
Toronto , , Canada
Cancer Care Manitoba
Winnipeg , , Canada
Tampere University Hospital
Tampere , , Finland
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 , , France
Orszagos Koranyi Pulmonologiai Intezet
Budapest , , Hungary
Szent Borbala Korhaz
Tatabanya , , Hungary
Torokbalinti Tudogyogyintezet
Torokbalint , , Hungary
Azienda Ospedaliero-Universitaria delle Marche
Ancona , 60126, 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
Istituto Europeo di Oncologia
Milano , , Italy
IRCCS Ospedale San Raffaele
Milan , , 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 , , Italy
PanOncology Trials, LLC
Rio Piedras , , Puerto Rico
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 , , Russian Federation
National Cancer Centre Singapore
Singapore , , Singapore
Oncocare Cancer Centre
Singapore , , Singapore
Tan Tock Seng Hospital
Singapore , , Singapore
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 , , Spain
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 , , Taiwan
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 Kingdom

How clear is this clinincal trial information?

Study is for people with:

Lung Cancer

Phase:

Phase 2

Estimated Enrollment:

497

Study ID:

NCT03175224

Recruitment Status:

Recruiting

Sponsor:


Apollomics Inc.

How clear is this clinincal trial information?

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