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

NCT03175224 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: APL-101-01
• Study Type: interventional
• Target: 497
• Locations: 11 countries
• Sites: 35

Brief 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)

Conditions

Solid Tumors; Advanced Cancer; Renal Cancer; Gastric Cancer; Gastroesophageal Junction Adenocarcinoma; NSCLC; Lung Cancer; Brain Tumor; Glioblastoma Multiforme; EGFR Gene Mutation; MET Amplification; HGF; Thyroid Cancer; Pancreatic Cancer; Colon Cancer; MET Alteration; MET Fusion; Exon 14 Skipping

Keywords

Advanced Solid Tumor; Relapsed Solid Tumor; Recurrent Solid Tumor; cMet exon 14 skipping; cMet fusion; GBM; HGF; EGFR positive

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (6)

• Median duration of response (DOR) per IRC.

  Approximately 2 years

• ORR per investigator assessment based on RECIST v1.1.

  Approximately 2 years

• Median DOR per investigator assessment.

  Approximately 2 years

• 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).

  Approximately 2 years

• Median time to progression (TTP).

  Approximately 2 years

Study Arms (9)

NSCLC Exon 14 Skip Treatment Naive

EXPERIMENTAL

Cohort A-1: APL-101 Oral Capsules

Drug: APL-101 Oral Capsules

NSCLC Exon 14 Skip Previously Treated

EXPERIMENTAL

Cohort A-2: APL-101 Oral Capsules

Drug: APL-101 Oral Capsules

NSCLC Exon 14 MET Inhibitor Experienced

EXPERIMENTAL

Cohort B: APL-101 Oral Capsules

Drug: APL-101 Oral Capsules

Basket of tumor types MET amplification except for primary CNS tumors

EXPERIMENTAL

Cohort C: APL-101 Oral Capsules

Drug: APL-101 Oral Capsules

NSCLC MET amplification and EGFR wild-type

EXPERIMENTAL

Cohort C-1: APL-101 Oral Capsules

Drug: APL-101 Oral Capsules

EGFR positive NSCLC MET amplification as an acquired resistance

EXPERIMENTAL

Cohort C-2: APL-101 Oral Capsules + Standard of Care EGFR Inhibitor

Drug: APL-101 Oral Capsules

Basket of solid tumor with MET gene fusions except for primary CNS tumors

EXPERIMENTAL

Cohort D: APL-101 Oral Capsules

Drug: APL-101 Oral Capsules

Primary CNS tumors with MET alterations

EXPERIMENTAL

Cohort E: APL-101 Oral Capsules

Drug: APL-101 Oral Capsules

Basket of tumor types wild-type MET with over-expression of HGF and MET

EXPERIMENTAL

Cohort F: APL-101 Oral Capsules

Drug: APL-101 Oral Capsules

Interventions

APL-101 Oral Capsules DRUG

Subjects will receive APL-101 capsules BID for oral administration.

Also known as: PLB-1001, CBI-3103, Bozitinib, CBT-101, Vebreltinib

Basket of solid tumor with MET gene fusions except for primary CNS tumors; Basket of tumor types MET amplification except for primary CNS tumors; Basket of tumor types wild-type MET with over-expression of HGF and MET; EGFR positive NSCLC MET amplification as an acquired resistance; NSCLC Exon 14 MET Inhibitor Experienced; NSCLC Exon 14 Skip Previously Treated; NSCLC Exon 14 Skip Treatment Naive; NSCLC MET amplification and EGFR wild-type; Primary CNS tumors with MET alterations

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men and women 18 years of age or older.
• 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 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Apollomics Inc.: lead

Study Sites (35)

Cedars-Sinai Medical Center - Samuel Oschin Comprehensive Cancer Institute

Los Angeles, California, 90048, United States

RECRUITING

Moffitt

Tampa, Florida, 33612, United States

ACTIVE NOT RECRUITING

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

ACTIVE NOT RECRUITING

University of North Carolina

Chapel Hill, North Carolina, 27599, United States

RECRUITING

Penn State Milton S. Hershey Medical Center

Hershey, Pennsylvania, 17033, United States

RECRUITING

University of Wisconsin

Madison, Wisconsin, 53792, United States

RECRUITING

St Vincents Hospital Melbourne

Melbourne, Australia

RECRUITING

Cross Cancer Institute

Edmonton, Canada

RECRUITING

McGill University Health Center - Research Institute

Montreal, Canada

RECRUITING

Princess Margaret Hospital

Toronto, Canada

RECRUITING

Cancer Care Manitoba

Winnipeg, Canada

RECRUITING

CHRU de Brest - Hôpital Morvan

Brest, France

RECRUITING

Centre Leon Berard

Lyon, France

RECRUITING

Centre d'Essais Precoces en Cancerologie de Marseille

Marseille, France

RECRUITING

Hopital Bichat - Claude Bernard - AP-HP

Paris, France

RECRUITING

Gustave Roussy

Villejuif, France

RECRUITING

Orszagos Koranyi Pulmonologiai Intezet

Budapest, Hungary

RECRUITING

Komarom-Esztergom Varmegyei Szent Borbala Korhaz

Tatabánya, Hungary

RECRUITING

IRCCS Azienda Ospedaliero-Universitaria di Bologna - Policlinico di Sant'Orsola

Bologna, Italy

RECRUITING

Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori

Meldola, Italy

RECRUITING

IRCCS Ospedale San Raffaele

Milan, Italy

RECRUITING

Istituto Europeo di Oncologia

Milan, Italy

RECRUITING

Istituto Oncologico Veneto-I.R.C.C.S. - Ospedale Busonera

Padua, Italy

RECRUITING

Private Medical Institution Euromedservice

Saint Petersburg, Russia

ACTIVE NOT RECRUITING

National Cancer Centre Singapore

Singapore, Singapore

RECRUITING

Hospital Germans Trias i Pujol

Badalona, Spain

RECRUITING

Hospital Clinic Barcelona

Barcelona, Spain

RECRUITING

Hospital del Mar

Barcelona, Spain

RECRUITING

Institut Catala d'Oncologia - L'Hospitalet

Barcelona, Spain

RECRUITING

Hospital Universitario 12 de Octubre

Madrid, Spain

RECRUITING

Instituto Valenciano de Oncologia

Valencia, Spain

RECRUITING

National Taiwan University Hospital

Taipei, Taiwan

RECRUITING

University College London Hospital

London, United Kingdom

RECRUITING

The Christie NHS Foundation Trust

Manchester, United Kingdom

RECRUITING

Royal Marsden Hospital - Surrey

Surrey Quays, United Kingdom

RECRUITING

Related Links

• Apollomics, Inc. website

MeSH Terms

Conditions

Kidney Neoplasms; Stomach Neoplasms; Lung Neoplasms; Brain Neoplasms; Glioblastoma; Thyroid Neoplasms; Pancreatic Neoplasms; Colonic Neoplasms

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Central Nervous System Neoplasms; Nervous System Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Endocrine Gland Neoplasms; Head and Neck Neoplasms; Endocrine System Diseases; Thyroid Diseases; Pancreatic Diseases; Colorectal Neoplasms; Intestinal Neoplasms; Colonic Diseases; Intestinal Diseases

Study Officials

• Mythili Sangem

  Apollomics Inc.

  STUDY DIRECTOR

Central Study Contacts

Emma (Xiaoning) Cai

CONTACT

+1 6502094055; clinops@apollomicsinc.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 1, 2017
• First Posted: June 5, 2017
• Study Start: September 27, 2017
• Primary Completion: March 30, 2026
• Study Completion (Estimated): November 30, 2026
• Last Updated: June 27, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

SG (1); AU (1); GB (3); ES (6); FR (5); IT (5); RU (1); TW (1); US (6); CA (4); HU (2)