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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03175224




Registration number
NCT03175224
Ethics application status
Date submitted
1/06/2017
Date registered
5/06/2017

Titles & IDs
Public title
APL-101 Study of Subjects With NSCLC With c-Met EXON 14 Skip Mutations and c-Met Dysregulation Advanced Solid Tumors
Scientific 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
Secondary ID [1] 0 0
APL-101-01
Universal Trial Number (UTN)
Trial acronym
SPARTA
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Solid Tumors 0 0
Advanced Cancer 0 0
Renal Cancer 0 0
Gastric Cancer 0 0
Gastroesophageal Junction Adenocarcinoma 0 0
NSCLC 0 0
Lung Cancer 0 0
Brain Tumor 0 0
Glioblastoma Multiforme 0 0
EGFR Gene Mutation 0 0
MET Amplification 0 0
HGF 0 0
Thyroid Cancer 0 0
Pancreatic Cancer 0 0
Colon Cancer 0 0
MET Alteration 0 0
MET Fusion 0 0
Exon 14 Skipping 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lung - Mesothelioma
Cancer 0 0 0 0
Lung - Non small cell
Cancer 0 0 0 0
Lung - Small cell
Cancer 0 0 0 0
Brain
Cancer 0 0 0 0
Kidney

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - APL-101 Oral Capsules

Experimental: NSCLC Exon 14 Skip Treatment Naive - Cohort A-1: APL-101 Oral Capsules

Experimental: NSCLC Exon 14 Skip Previously Treated - Cohort A-2: APL-101 Oral Capsules

Experimental: NSCLC Exon 14 MET Inhibitor Experienced - Cohort B: APL-101 Oral Capsules

Experimental: Basket of tumor types MET amplification except for primary CNS tumors - Cohort C: APL-101 Oral Capsules

Experimental: NSCLC MET amplification and EGFR wild-type - Cohort C-1: APL-101 Oral Capsules

Experimental: EGFR positive NSCLC MET amplification as an acquired resistance - Cohort C-2: APL-101 Oral Capsules + Standard of Care EGFR Inhibitor

Experimental: Basket of solid tumor with MET gene fusions except for primary CNS tumors - Cohort D: APL-101 Oral Capsules

Experimental: Primary CNS tumors with MET alterations - Cohort E: APL-101 Oral Capsules

Experimental: Basket of tumor types wild-type MET with over-expression of HGF and MET - Cohort F: APL-101 Oral Capsules


Treatment: Drugs: APL-101 Oral Capsules
Subjects will receive APL-101 capsules BID for oral administration.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Objective response rate (ORR = CR + PR) per IRC committee (BIRC) based on RECIST v1.1 (or relevant criteria per tumor type)
Timepoint [1] 0 0
From time of informed consent signature through completion of treatment (1 cycle = 28 days) or progression
Secondary outcome [1] 0 0
Median duration of response (DOR) per IRC.
Timepoint [1] 0 0
Approximately 2 years
Secondary outcome [2] 0 0
ORR per investigator assessment based on RECIST v1.1.
Timepoint [2] 0 0
Approximately 2 years
Secondary outcome [3] 0 0
Median DOR per investigator assessment.
Timepoint [3] 0 0
Approximately 2 years
Secondary outcome [4] 0 0
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).
Timepoint [4] 0 0
Approximately 2 years
Secondary outcome [5] 0 0
Median time to progression (TTP).
Timepoint [5] 0 0
Approximately 2 years
Secondary outcome [6] 0 0
Progression Free Survival (PFS) and overall survival (OS) at 6, 12, 18 and 24 months
Timepoint [6] 0 0
Approximately 3 years

Eligibility
Key inclusion criteria
Major

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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
27/09/2017
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
30/11/2026
Actual
Sample size
Target
497
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 0 0
Flinders Medical Centre - Bedford Park
Recruitment hospital [2] 0 0
Border Medical Oncology - Albury
Recruitment hospital [3] 0 0
Peninsula and Southeast Oncology - Frankston
Recruitment hospital [4] 0 0
St Vincents Hospital Melbourne - Melbourne
Recruitment hospital [5] 0 0
Sir Charles Gairdner Hospital - Nedlands
Recruitment hospital [6] 0 0
Calvary Central Districts Hospita - North Adelaide
Recruitment postcode(s) [1] 0 0
- Bedford Park
Recruitment postcode(s) [2] 0 0
- Albury
Recruitment postcode(s) [3] 0 0
- Frankston
Recruitment postcode(s) [4] 0 0
- Melbourne
Recruitment postcode(s) [5] 0 0
- Nedlands
Recruitment postcode(s) [6] 0 0
- North Adelaide
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
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United States of America
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Delaware
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United States of America
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Florida
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United States of America
State/province [4] 0 0
Maryland
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United States of America
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Massachusetts
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United States of America
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Minnesota
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United States of America
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Missouri
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United States of America
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North Carolina
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Ohio
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United States of America
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Pennsylvania
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South Carolina
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United States of America
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Tennessee
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Texas
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West Virginia
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United States of America
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Wisconsin
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Canada
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Quebec
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Canada
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Edmonton
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Canada
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Montréal
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Canada
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Toronto
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Canada
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Winnipeg
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Finland
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Tampere
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France
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Brest
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France
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Lille
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France
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Lyon
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France
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Marseille
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France
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Paris
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France
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Rennes
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France
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Villejuif
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Hungary
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Budapest
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Hungary
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Tatabanya
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Hungary
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Torokbalint
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Italy
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Ancona
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Italy
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Bologna
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Italy
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Catania
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Italy
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Meldola
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Italy
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Milano
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Italy
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Milan
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Italy
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Padova
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Italy
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Torino
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Puerto Rico
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Rio Piedras
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Russian Federation
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Arkhangelsk
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Russian Federation
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Otradnoye
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Russian Federation
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Saint Petersburg
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Russian Federation
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Saransk
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Russian Federation
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St. Petersburg
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Russian Federation
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Volgograd
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Singapore
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Singapore
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Spain
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Badalona
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Spain
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Barcelona
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Spain
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Madrid
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Spain
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Oviedo
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Spain
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Sevilla
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Spain
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Valencia
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Taiwan
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Taichung
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Taiwan
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Tainan
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Taiwan
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Taipei City
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Taiwan
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Taoyuan City
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United Kingdom
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London
Country [59] 0 0
United Kingdom
State/province [59] 0 0
Manchester
Country [60] 0 0
United Kingdom
State/province [60] 0 0
Surrey Quays

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Apollomics Inc.
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Peony Yu
Address 0 0
Apollomics Inc.
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Emma (Xiaoning) Cai
Address 0 0
Country 0 0
Phone 0 0
6502094055
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT03175224