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    Summary
    EudraCT Number:2019-001757-54
    Sponsor's Protocol Code Number:APL-101-01
    National Competent Authority:UK - MHRA
    Clinical Trial Type:EEA CTA
    Trial Status:GB - no longer in EU/EEA
    Date on which this record was first entered in the EudraCT database:2020-03-02
    Trial results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedUK - MHRA
    A.2EudraCT number2019-001757-54
    A.3Full title of the trial
    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
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    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
    A.3.2Name or abbreviated title of the trial where available
    SPARTA
    A.4.1Sponsor's protocol code numberAPL-101-01
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT03175224
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorApollomics, Inc.
    B.1.3.4CountryUnited States
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportApollomics, Inc.
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationMedpace
    B.5.2Functional name of contact pointClinical Trial Manager
    B.5.3 Address:
    B.5.3.1Street Address5375 Medpace Way
    B.5.3.2Town/ cityCincinnati
    B.5.3.3Post code45227
    B.5.3.4CountryUnited States
    B.5.4Telephone number+1513579991112160
    B.5.6E-maile.lefkovitz@medpace.com
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameAPL-101
    D.3.2Product code APL-101
    D.3.4Pharmaceutical form Capsule
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNCBT-101, Bozitinib
    D.3.9.1CAS number 1440964-89-5
    D.3.9.2Current sponsor codeAPL-101
    D.3.9.3Other descriptive nameAPL-101
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number100
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Non-Small Cell Lung Cancer with c-Met EXON 14 Skip Mutations and c-Met Dysregulation Advanced Solid Tumors
    E.1.1.1Medical condition in easily understood language
    a solid tumor carrying c-Met dysregulated genetic alterations or Non-Small Cell Lung Cancer (NSCLC) carrying MET EXON 14 skip mutations
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.1
    E.1.2Level LLT
    E.1.2Classification code 10065252
    E.1.2Term Solid tumor
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.1
    E.1.2Level PT
    E.1.2Classification code 10061873
    E.1.2Term Non-small cell lung cancer
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    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.
    E.2.2Secondary objectives of the trial
    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).
    E.2.3Trial contains a sub-study No
    E.3Principal 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-MET; KIF5B-MET
    d. or other c-Met mutations in Dose Escalation (400 mg Cohort)
    6. Local/archival result of a positive c-Met dysregulation is required. In Ph 2, Cohorts A and D require provision of tumor tissue samples. For Cohorts B and C, provision of tumor tissue or plasma sample for entry is acceptable.
    7. Across Ph 2 five cohorts, treated or untreated asymptomatic parenchymal CNS disease or leptomeningeal disease is allowed.
    8. Measurable disease according to RECIST v1.1. (or relevant criteria per tumor type).
    9. ECOG performance status of 0–1.
    10. Acceptable organ function, as evidenced by the following laboratory data during Screening period:
    a.AST and alanine aminotransferase (ALT) ≤ 2.5 x ULN
    b.Total serum bilirubin ≤ 1.5 x ULN
    c.For subjects with liver metastases: Total bilirubin ≤ 3.0 x ULN, AST/ ALT ≤ 5 x ULN
    d.Absolute neutrophil count (ANC) ≥ 1500 cells/mm3 (1.5 x 109/L)
    e.Platelet count ≥ 100,000 cells/mm3 (100 x 109/L)
    f.Serum creatinine levels ≤ 1.5 ULN or CrCl ≥ 60 mL/min
    g.Hemoglobin ≥ 9 g/dL
    11.For all prior anticancer treatment, including radiotherapy,chemotherapy or targeted agents or hormonal therapy, 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.
    12.Adequate cardiac function or normal cardiac function with LVEF ≥ 50% at screening.
    E.4Principal 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.
    E.5 End points
    E.5.1Primary 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).
    E.5.1.1Timepoint(s) of evaluation of this end point
    Timepoints are described within the text in section E.5.1
    E.5.2Secondary 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.
    E.5.2.1Timepoint(s) of evaluation of this end point
    Timepoints are described within the text in section E.5.2
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy No
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic Yes
    E.6.8Bioequivalence No
    E.6.9Dose response Yes
    E.6.10Pharmacogenetic Yes
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) Yes
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other Yes
    E.7.1.3.1Other trial type description
    Phase 1/2 study with Phase 1 clinical experience
    E.7.2Therapeutic exploratory (Phase II) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled No
    E.8.1.1Randomised No
    E.8.1.2Open Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    E.8.1.5Parallel group No
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) Information not present in EudraCT
    E.8.2.2Placebo Information not present in EudraCT
    E.8.2.3Other Information not present in EudraCT
    E.8.3 The trial involves single site in the Member State concerned No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned3
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA47
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Australia
    Belgium
    Canada
    Finland
    France
    Germany
    Hong Kong
    Hungary
    Italy
    Russian Federation
    Singapore
    Spain
    Taiwan
    Ukraine
    United Kingdom
    United States
    E.8.7Trial has a data monitoring committee Yes
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    6-months post last subject treatment
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years5
    E.8.9.1In the Member State concerned months6
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years5
    E.8.9.2In all countries concerned by the trial months6
    E.8.9.2In all countries concerned by the trial days0
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 121
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 80
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception Yes
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state9
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 80
    F.4.2.2In the whole clinical trial 201
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    None (SOC)
    G. Investigator Networks to be involved in the Trial
    G.4 Investigator Network to be involved in the Trial: 1
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2020-04-28
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2020-06-01
    P. End of Trial
    P.End of Trial StatusGB - no longer in EU/EEA
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