Lung Cancer Clinical Trial
— SPARTAOfficial title:
Phase 1 / 2 Multicenter Study of the Safety, Pharmacokinetics, and Preliminary Efficacy of APL-101 in Subjects With Non-Small Cell Lung Cancer With c-Met EXON 14 Skip Mutations and c-Met Dysregulation Advanced Solid Tumors
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)
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. |
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 |
Lead Sponsor | Collaborator |
---|---|
Apollomics Inc. |
United States, Australia, Canada, Finland, France, Hungary, Italy, Puerto Rico, Russian Federation, Singapore, Spain, Taiwan, United Kingdom,
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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