Non-Small Cell Lung Cancer with c-Met EXON 14 Skip Mutations and c-Met Dysregulation Advanced Solid Tumors MedDRA version: 21.1 Level: LLT Classification code 10065252 Term: Solid tumor System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 21.1 Level: PT Classification code 10061873 Term: Non-small cell lung cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Sponsors
Apollomics, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Men/women = 18 years of age or older able to understand and sign ICF before study. 3. For Ph 1, histologically and/or cytological confirmed unresectable or metastatic solid malignancy, refractory to standard therapies with no more than three prior lines of therapy. 4.For Ph 2, five cohorts will be enrolled: 4a. Cohort A-1: EXON 14 NSCL Cancer – c-Met inhibitor naïve (1L) a.Histologically or cytologically confirmed NSCLC with EXON 14 skip mutations; All histologies (pulmonary sarcomatoid carcinoma and squamous) b.Unresectable or metastatic disease (Stage 3b/4) d.Treatment naïve subjects in first-line e.Not received any c-Met inhibitor Cohort A-2: EXON 14 NSCL Cancer – c-Met inhibitor naïve (= 2L) a.Histologically or cytologically confirmed NSCLC with EXON 14 skip mutations b.All histologies, including pulmonary sarcomatoid carcinoma and squamous c.Unresectable or metastatic disease (Stage 3b/4) d.Pretreated subjects refractory to or intolerable to standard therapies with no more than three lines of prior therapy e.Not received any c-Met inhibitor 4b. Cohort B: EXON 14 NSCL Cancer – c-Met inhibitor experienced a.Histologically or cytologically confirmed NSCLC with EXON 14 skip mutations b.All histologies, including pulmonary sarcomatoid carcinoma and squamous c.Unresectable or metastatic disease (Stage 3b/4) d.Refractory to standard therapies with no more than three prior lines of therapy e.Radiographic progression on any c-Met inhibitor at any point in the past 4c. Cohort C: Basket Tumor Types (c-Met high-level amplifications) a.Any tumor type regardless of histology, including osimertinib relapsed/refractory NSCLC, excluding NSCLC EXON 14 skip mutation, that meets inclusion criteria c-Met high-level amplification b.Unresectable or metastatic disease, refractory to standard therapies with no more than three prior lines of therapy c.Not received any c-Met inhibitor 4d. Cohort D: Basket Tumor Types (c-Met fusions) a.Any other tumor type histology that meets inclusion criteria c-Met fusions b.Unresectable or metastatic disease, refractory to standard therapies with no more than three prior lines of therapy c.Not received any c-Met inhibitor 5.Abnormal c-Met dysregulation, by tissue and/or plasma, defined as the following from local/archival molecular pre-screening evaluations. Phase 1 (100, 200, and 300 mg Cohorts) a.c-Met overexpression by IHC 2+ = 50% of tumor cells b.or c-Met amplification (c-Met/Cep-7 ratio = 2.2 or GCN = 6 gene copy) c.or c-Met EXON 14 skip mutation per NGS or RT-PCR d.or c-Met fusions including the following, but not limited to: BAIAP2L1-MET; C8orf34-MET; CAPZA2-MET; DCTN1-MET; EPS15-MET; LRRFIP1-MET; MET-MET; OXR1-MET; PPFIBP1-MET; PTPRZ1-MET; TFG-MET; TPR-MET; TRIM4-MET; ZKSCAN1-MET; KIF5B-MET and any other known c-Met activating mutations Phase 1 (400 mg Cohort) and Phase 2 RP2D a.c-Met high-level amplification (c-Met/Cep-7 ratio of = 2.2 or GCN of = 6 copy). A minimum of five subjects of the high-level amplification (c-Met/Cep-7 ratio of = 5 or GCN = 10 gene copy) for the Stage 1 of the Simon 2 stage design is required) b.or c-Met EXON 14 skip mutation per NGS c.or c-Met fusions including the following, but not limited to: BAIAP2L1-MET; C8orf34-MET; CAPZA2-MET; DCTN1-MET; EPS15-MET; LRRFIP1-MET; MET-MET; OXR1-MET; PPFIBP1-MET; PTPRZ1-MET; TFG-MET; TPR-MET; TRIM4-MET; ZKSCAN1-MET; KIF5B-MET d. or other c-Met mutations in Dose Escalation (400 mg Cohort) 6. Local/archival
Exclusion criteria
Exclusion criteria: 1.Hypersensitivity to APL-101, excipients of the drug product, or other components of the study treatment regimen. 2.Known mutation/gene rearrangement of EGFR (except for Cohort C), ALK, ROS1, RET, NTRK, KRAS and BRAF. 3.Use or intended use of any other investigational product, including herbal medication 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. Screening for chronic conditions is not required. 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.History of, or currently, or at risk for, cardiac disease (e.g., long QT syndrome [> 450 msec QTcF or concurrent treatment with any medication that prolongs QT interval). 7.History of human immunodeficiency virus (HIV), or 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. If history is unclear, a test at Screening will be required. 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 (e.g., Crohn’s, ulcerative colitis, active inflammatory bowel disease, uncontrolled nausea, vomiting, diarrhea, or malabsorption syndrome). 11.Women who are breastfeeding. 12.Subjects with complications from prior radiation therapy will not be eligible until AEs return to baseline or = Grade 1. 13.Pregnant or breastfeeding woman.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Phase 1 Primary Objective •To assess overall safety and tolerability, determine the dose limiting toxicities (DLTs), and identify the recommended Phase 2 dose (RP2D). Phase 2 Primary Objective •To assess efficacy by overall response rate (ORR) and duration of response (DOR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. or relevant evaluation criteria per tumor type. ;Secondary Objective: Phase 1/2 Secondary Objectives •To assess incidence of serious adverse events (SAEs) and adverse events (AEs) by relationship and severity grade. •To determine the pharmacokinetic (PK) parameters of orally administered APL-101. •To assess efficacy by clinical benefit rate (CBR: CR + PR + SD = 4 cycles), time to progression (TTP), progression free survival (PFS), per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 (or relevant evaluation criteria per tumor type) and overall survival (OS). ;Primary end point(s): Phase 1 Primary Endpoint •Estimate the maximum tolerated dose (MTD) and the incidence of DLTs in Cycle 1, sustained Grade 2 adverse events, dose reductions, dose interruptions and any occurrences of delayed toxicities and other AEs to determine the RP2D dosing of APL-101. Phase 2 Primary Endpoint •Objective response rate (ORR = CR + PR) and median duration of response (DOR) per investigator assessment based on RECIST v1.1. (or relevant criteria per tumor type). ;Timepoint(s) of evaluation of this end point: Timepoints are described within the text in section E.5.1 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Phase 1/2 Secondary Endpoint(s) •Incidence of SAEs and AEs by relationship and severity grade, and incidence of SAEs/AEs leading to dose reduction, interruption or discontinuation of study treatment. •Pharmacokinetic parameters: Cmax, Cmin, AUC0-t, AUC0-?, Tmax, elimination T½, and other secondary PK parameters of APL-101 in all subjects during Cycle 1, and APL-101 metabolites if applicable. •Antitumor activity by clinical benefit rate (CR + PR + SD = 4 cycles) per RECIST v1.1. (or relevant criteria per tumor type). •Median time to progression (TTP). •Progression free survival (PFS) and overall survival (OS) at 6, 12, 18 and 24 months. ;Timepoint(s) of evaluation of this end point: Timepoints are described within the text in section E.5.2 | — |
Countries
Australia, Belgium, Canada, Finland, France, Germany, Hong Kong, Hungary, Italy, Russian Federation, Singapore, Spain, Taiwan, Ukraine, United Kingdom, United States
Contacts
Public ContactClinical Trial Manager
Medpace
Outcome results
None listed