Clinical trial to evaluate safety and effectiveness of APL-101 for the treatment of advanced c-Met expressing solid tumors, including NSCLC, and to find the best dose

Phase 1

• Conditions: on-Small Cell Lung Cancer with c-Met EXON 14 Skip Mutations and c-Met Dysregulation Advanced Solid Tumors; MedDRA version: 21.1Level: LLTClassification code 10065252Term: Solid tumorSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 21.1Level: PTClassification code 10061873Term: Non-small cell lung cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2019-001757-54-GB
• Lead Sponsor: Apollomics, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2020-03-02
• Last Update Posted: 3 November 2020

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 201

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 3 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 3 lines of prior therapy in the metastatic setting
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 3 prior lines of therapy in the metastatic setting
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 3 prior lines of therapy in the metastatic setting
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 3 prior lines of therapy in the metastatic setting
c.Not received any c-Met inhibitor
5.Abnormal c-Met dysregulation, by tissue and/or plasma, defined as the following from archival/local results or 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-M

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.Unstable angina or myocardial infarction within 1 year prior to first dose of APL-101, or symptomatic or unstable arrhythmia requiring medical therapy, or history of congenital prolonged QT syndrome or whose corrected QT interval by Fridericia formula (QTcF) at screening is prolonged (> 450 msec based on the average of 3 measurements) or concurrent treatment with any medication that prolongs QT interval.
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 (HIV) positive patients who are not clinically stable or controlled on their medication (i.e. asymptomatic patients 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. Patients on contraindicated medications should be evaluated and replaced with alternate medications with less risk of drug-drug interaction). 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.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified