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Clinical Trials List

Protocol NumberAPL-101-01 (SPARTA)
NCT Number(ClinicalTrials.gov Identfier)NCT03175224

2020-04-01 - 2028-12-31

Phase I/II

Not yet recruiting1

Recruiting5

ICD-10C34.90

Malignant neoplasm of unspecified part of unspecified bronchus or lung

ICD-10C34.91

Malignant neoplasm of unspecified part of right bronchus or lung

ICD-10C34.92

Malignant neoplasm of unspecified part of left bronchus or lung

ICD-10C7A.090

Malignant carcinoid tumor of the bronchus and lung

ICD-10Z51.12

Encounter for antineoplastic immunotherapy

ICD-9162.9

Malignant neoplasm of bronchus and lung, unspecified

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

  • Trial Applicant

    MEDPACE TAIWAN LIMITED

  • Sponsor

  • Trial scale

    Multi-Regional Multi-Center

  • Update

    2025/08/20

Investigators and Locations

Principal Investigator Cheng-Ta Yang 無
Linkou Chang Gung Medical Foundation

Co-Principal Investigator

The Actual Total Number of Participants Enrolled

0 Recruiting

Principal Investigator kang-Yun LEE 無
Taipei Medical University-Shuang Ho Hospital,Ministry of Health and Welfare

Co-Principal Investigator

The Actual Total Number of Participants Enrolled

0 Recruiting

Principal Investigator 曹朝榮 無
Chi Mei Hospital, Liouying

Co-Principal Investigator

The Actual Total Number of Participants Enrolled

0 Recruiting

Principal Investigator Han-Pin Kuo 無
Taipei Medical University Hospital

Co-Principal Investigator

The Actual Total Number of Participants Enrolled

0 Recruiting

Principal Investigator James Chih-Hsin Yang Division of Hematology & Oncology
National Taiwan University Hospital

Co-Principal Investigator

The Actual Total Number of Participants Enrolled

0 Recruiting

Principal Investigator TSUNG -YING YANG Division of Thoracic Medicine
Taichung Veterans General Hospital

Co-Principal Investigator

The Actual Total Number of Participants Enrolled

0 Not yet recruiting

Condition/Disease

c-Met EXON 14 Skip Mutations and c-Met Dysregulation Advanced Solid Tumors

Objectives

Study Objectives: 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. 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). Phase 1/2 Exploratory Objective • To evaluate potential pharmacodynamic (PD) biomarkers of APL-101 and its correlation to the PK profile. • To evaluate relationship of relevant biomarkers, including c-Met protein expression, amplification, and/or mutations to clinical response.

Test Drug

APL-101

Active Ingredient

APL-101

Dosage Form

capsule

Dosage

100 mg

Endpoints

Study Endpoints:
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).

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.

Phase 1/2 Exploratory Endpoint(s)
• Status of MET genetic alterations including MET amplification, EXON 14 skip mutations,
fusions, and other oncogenic mutations.
• c-Met protein expression by IHC.
• Other potential biomarkers of APL-101 activity as they become known.

Inclution Criteria

1. Able to understand and comply with the study procedures, understand the risks involved in the
study, and provide written informed consent before any study-specific procedure is performed.
2. Men and women 18 years of age or older.
3. For Phase 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 Phase 2, five cohorts will be enrolled: Cohort A-1: NSCLC EXON 14 skip mutation (c-Met
naïve) for first line treatment, Cohort A-2: NSCLC EXON 14 skip mutation (c-Met naïve)
pretreated subjects with no more than 3 lines of prior therapy in the metastatic setting, Cohort B:
NSCLC EXON 14 skip mutation (c-Met experienced; radiographic progression on prior c-Met
inhibitor), Cohort C: basket of tumor types with c-Met high level amplification (NSCLC EXON
14 skip mutation excluded), Cohort D: basket of tumor type with c-Met fusions.
4a. Cohort A-1: EXON 14 Non-Small-Cell Lung Cancer – c-Met inhibitor naïve (1L)
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. Treatment naïve subjects in first-line
e. Not received any c-Met inhibitor (e.g., crizotinib, capmatinib, savolitinib, etc.)
4b. Cohort A-2: EXON 14 Non-Small-Cell Lung 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 (if available, must
include anti-PD-1/PD-L1 based systemic therapy) with no more than three lines of prior
therapy in the metastatic setting
e. Not received any c-Met inhibitor (e.g., crizotinib, capmatinib, savolitinib, etc.)
4c. Cohort B: EXON 14 Non-Small-Cell Lung 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 in the
metastatic setting
e. Radiographic progression on any c-Met inhibitor (e.g., crizotinib, capmatinib,
savolitinib, etc.) at any point in the past
4d. 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 in the metastatic setting
c. Not received any c-Met inhibitor (e.g., crizotinib, capmatinib, savolitinib, etc.)
4e. 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 in the metastatic setting
c. Not received any c-Met inhibitor (e.g., crizotinib, capmatinib, savolitinib, etc.)
5. Abnormal c-Met dysregulation, by tissue and/or plasma, defined as the following from
archival/local results or molecular pre-screening evaluations. Refer to Section 4.1 (Table 8) for
further clarification on eligible c-Met dysregulations.
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 Phase 2, Cohorts A and D
require provision of tumor tissue samples (archival or fresh tumor biopsy). For Cohorts B and C,
provision of tumor tissue (archival or fresh tumor biopsy) or plasma sample for entry is
acceptable.
7. Across Phase 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. Eastern Cooperative Oncology Group (ECOG) performance status of 0–1.
10. Acceptable organ function, as evidenced by the following laboratory data during Screening
period:
a. Aspartate aminotransferase (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 Creatinine Clearance (CrCl) ≥ 60 mL/min as
calculated by the Cockcroft-Gault method
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 (≤ NYHA class II) or normal cardiac function with left ventricular
ejection fraction (LVEF) ≥ 50% at screening.
13. Women of child-bearing potential (WOCBP) must have a negative serum or β-human chorionic
gonadotropin (β-hCG) at screening or evidence of surgical sterility or evidence of postmenopausal status. Post-menopausal status is defined as any of the following: natural menopause
with menses > 1 year ago, radiation or chemotherapy induced oophorectomy with menses > 1
year ago and follicle stimulating hormone (FSH) level in the menopausal range.
14. All subjects with reproductive potential must agree, and site must document as such, the use of
effective contraceptive measures (e.g., oral contraceptives, intrauterine device, or double barrier
method of condom and spermicide) during the study and 7 months (WOCBP) or 4 months (men)
following the last dose of study drug.
Notes:
A postmenopausal woman will be defined as having no menses for 12 months without an
alternative medical cause. Male sterility will be defined as only men sterilized surgically. For
male subjects with a pregnant partner, a condom should be used for contraception. For male
subjects with a non-pregnant female partner of child-bearing potential and woman of childbearing potential one of the following birth control methods with a failure rate of less than 1%
per year when used consistently and correctly are recommended:
a. Combined estrogen and progesterone containing hormonal contraception associated with
inhibition of ovulation given orally, intravaginally, or transdermally
b. Progesterone-only hormonal contraception associated with inhibition of ovulation given
orally, by injection, or by implant
c. Intrauterine device (IUD)
d. Intrauterine hormone-releasing system (IUS)
e. Bilateral tubal occlusion
f. Vasectomized partner
g. Sexual abstinence
Birth control methods unacceptable for this clinical trial are:
a. Periodic abstinence (calendar, symptothermal, or post-ovulation methods)
b. Withdrawal (coitus interruptus)
c. Spermicide only
d. Lactational amenorrhea method
15. Resolution of all acute chemotherapy, radiotherapy or surgery-related AEs to Grade ≤ 1, except
for alopecia.
16. No planned major surgery within 4 weeks of first dose of APL-101.
17. Willing and able to participate in all required evaluations and procedures in this study including
swallowing APL-101 in accordance administration schedule outlined.

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 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. 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,
symptomatic or unstable arrhythmia requiring medical therapy, history of congenital prolonged
QT syndrome, prolonged QT interval corrected by Fridericia formula (QTcF) at screening
(> 450 msec based on the average of 3 measurements), or concurrent treatment with a medication
that is a known risk for prolonging the QT interval (refer to Section 5.9, Concomitant Therapy).
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 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.

The Estimated Number of Participants

  • Taiwan

    18 participants

  • Global

    514 participants

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