APL-101 Study of Subjects With NSCLC With c-Met EXON 14 Skip Mutations and c-Met Dysregulation Advanced Solid Tumors (SPARTA)

• ClinicalTrials.gov Identifier: NCT03175224
• Recruitment Status: Recruiting
• First Posted: June 5, 2017
• Last Update Posted: May 10, 2024
• Sponsor: Apollomics Inc.
• Information provided by (Responsible Party): Apollomics Inc.

Tracking Information

• First Submitted Date: June 1, 2017
• First Posted Date: June 5, 2017
• Last Update Posted Date: May 10, 2024
• Actual Study Start Date: September 27, 2017
• Estimated Primary Completion Date: March 30, 2026 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 19, 2023)

Objective response rate (ORR = CR + PR) per IRC committee (BIRC) based on RECIST v1.1 (or relevant criteria per tumor type) [ Time Frame: From time of informed consent signature through completion of treatment (1 cycle = 28 days) or progression ]

Anti-tumor activity per RECIST v1.1, RANO criteria for CNS tumors, or relevant evaluation criteria per tumor type.

Original Primary Outcome Measures (submitted: June 1, 2017)

Number of participants with treatment related adverse events as assessed by Common Terminology Criteria for Adverse Events (CTCAE v4.03) [ Time Frame: From the time of informed consent signature to 30 days after discontinuation of study drug. ]

Adverse events, serious adverse events, and dose limiting toxicities according to the National Cancer Institute (NCI) Terminology Criteria for Adverse Events (CTCAE v4.03)

Current Secondary Outcome Measures (submitted: October 19, 2023)

• Median duration of response (DOR) per IRC. [ Time Frame: Approximately 2 years ]
  DOR per RECIST v1.1 criteria, RANO criteria for CNS tumors, or relevant evaluation criteria per tumor type.
• ORR per investigator assessment based on RECIST v1.1. [ Time Frame: Approximately 2 years ]
  ORR per RECIST v1.1 or relevant evaluation criteria per tumor type.
• Median DOR per investigator assessment. [ Time Frame: Approximately 2 years ]
  DOR per RECIST v1.1, RANO criteria for CNS tumors, or relevant evaluation criteria per tumor type.
• 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). [ Time Frame: Approximately 2 years ]
  Benefit rate per RECIST v1.1, RANO criteria for CNS tumors, or relevant evaluation criteria per tumor type.
• Median time to progression (TTP). [ Time Frame: Approximately 2 years ]
  TTP per RECIST v1.1 or relevant evaluation criteria per tumor type.
• Progression Free Survival (PFS) and overall survival (OS) at 6, 12, 18 and 24 months [ Time Frame: Approximately 3 years ]
  PFS and OS per RECIST v1.1 or relevant evaluation criteria per tumor type.

Original Secondary Outcome Measures (submitted: June 1, 2017)

• Determine the recommended Phase 2 dose and schedule [ Time Frame: Approximately 1 year ]
  Adverse events, serious adverse events, and dose limiting toxicities according to the National Cancer Institute (NCI) Terminology Criteria for Adverse Events (CTCAE v4.03)
• Area under the plasma concentration versus time curve (AUC) [ Time Frame: Up to 2 months (1 cycle = 28 days) ]
  AUC, 0 - infinity
• Maximum plasma concentration [ Time Frame: Up to 2 months (1 cycle = 28 days) ]
  Cmax
• Time to reach Cmax [ Time Frame: Up to 2 months (1 cycle = 28 days) ]
  Tmax
• Overall Response Rate [ Time Frame: Approximately 12 months ]
  Anti-tumor activity per RECIST v1.1
• Duration of Response [ Time Frame: Approximately 24 months ]
  Anti-tumor activity per RECIST v1.1
• Progression Free Survival [ Time Frame: Approximately 24 months ]
  Anti-tumor activity per RECIST v1.1

• Current Other Pre-specified Outcome Measures: Not Provided

Original Other Pre-specified Outcome Measures (submitted: June 1, 2017)

• Correlation of CBT-101 and c-MET at baseline and after study treatment. [ Time Frame: Approximately 24 months ]
• Correlation of CBT-101 and hepatocyte growth factor at baseline and after study treatment. [ Time Frame: Approximately 24 months ]
• Correlation of CBT-101 and soluble c-MET at baseline and after study treatment. [ Time Frame: Approximately 24 months ]

Descriptive Information

• Brief Title: APL-101 Study of Subjects With NSCLC With c-Met EXON 14 Skip Mutations and c-Met Dysregulation Advanced Solid Tumors
• Official 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

Brief Summary

To assess:

• efficacy of APL-101 as monotherapy for the treatment of NSCLC harboring MET Exon 14 skipping mutations, NSCLC harboring MET amplification, solid tumors harboring MET amplification, solid tumors harboring MET fusion, primary CNS tumors harboring MET alterations, solid tumors harboring wild-type MET with overexpression of HGF and MET
• efficacy of APL-101 as an add-on therapy to EGFR inhibitor for the treatment of NSCLC harboring EGFR activating mutations and developed acquired resistance with MET amplification and disease progression after documented CR or PR with 1st line EGFR inhibitors (EGFR-I)

Detailed Description

Phase 1 (lead-in stage of this study) enrollment has been completed.

In this Phase 2 study, efficacy, safety, and tolerability will be assessed in the following cohorts:

• Cohort A-1: NSCLC EXON 14 skip mutation, previously untreated, MET inhibitor naive (c-Met naïve, 1L)
• Cohort A-2: NSCLC EXON 14 skip mutation, previously treated with ≤ 3 prior lines in unresectable or metastatic setting, MET inhibitor naive (c-Met naïve, 2/3L)
• Cohort B: NSCLC EXON 14 skip mutation, previously treated with ≤ 3 prior lines in unresectable or metastatic setting, MET inhibitor experienced (c-Met experienced; progressed on prior c-Met inhibitor)
• Cohort C: basket of tumor types (e.g., NSCLC, upper gastrointestinal [GI], colorectal, hepatobiliary cancer) harboring MET amplification except for primary CNS tumors, previously treated or previously untreated but refused standard treatment, or if treatment was unavailable or unfeasible (≤ 3 prior lines in unresectable or metastatic setting), MET inhibitor naïve
• Cohort C-1: NSCLC harboring MET amplification and wild-type epidermal growth factor receptor (EGFR), previously treated; or untreated but refused standard treatment, or if treatment was unavailable or unfeasible (≤ 3 prior lines in unresectable or metastatic setting), MET inhibitor naïve
• Cohort C-2: EGFR positive NSCLC harboring MET amplification as an acquired resistance, documented response with first-line EGFR-Inhibitor (PR or CR per RECIST ≥ 12 weeks), radiological documentation of disease progression per RECIST on first-line EGFR inhibitor therapy, MET inhibitor naïve
• Cohort D: basket of tumor types except for primary CNS tumors harboring MET gene fusions (e.g., NSCLC, upper GI, colorectal, hepatobiliary cancer), previously treated; or previously untreated but refused standard treatment, or if treatment was unavailable or unfeasible (≤ 3 prior lines in unresectable or metastatic setting), MET inhibitor naïve
• Cohort E: primary CNS tumors with MET alterations (single or co-occurred MET fusion including PTPRZ1-MET [ZM] fusion, MET Exon 14 skipping mutation, or MET amplification), previously treated or previously untreated but refused standard treatment, or if treatment was unavailable or unfeasible (≤ 3 prior lines), MET inhibitor naïve
• Cohort F: basket of tumor types harboring wild-type MET with over-expression of HGF and MET (e.g., NSCLC, upper GI, colorectal, hepatobiliary cancer or primary CNS tumors), previously treated; or previously untreated but refused standard treatment, or if treatment was unavailable or unfeasible (≤ 3 prior lines in unresectable or metastatic setting), MET inhibitor naïve

• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Non-Randomized; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Solid Tumors
• Advanced Cancer
• Renal Cancer
• Gastric Cancer
• Gastroesophageal Junction Adenocarcinoma
• NSCLC
• Lung Cancer
• Brain Tumor
• Glioblastoma Multiforme
• EGFR Gene Mutation
• MET Amplification
• HGF
• Thyroid Cancer
• Pancreatic Cancer
• Colon Cancer
• MET Alteration
• MET Fusion
• Exon 14 Skipping

Intervention

Drug: APL-101 Oral Capsules

Subjects will receive APL-101 capsules BID for oral administration.

Other Names:

• PLB-1001
• CBI-3103
• Bozitinib
• CBT-101
• Vebreltinib

Study Arms

• Experimental: NSCLC Exon 14 Skip Treatment Naive
  Cohort A-1: APL-101 Oral Capsules
  Intervention: Drug: APL-101 Oral Capsules
• Experimental: NSCLC Exon 14 Skip Previously Treated
  Cohort A-2: APL-101 Oral Capsules
  Intervention: Drug: APL-101 Oral Capsules
• Experimental: NSCLC Exon 14 MET Inhibitor Experienced
  Cohort B: APL-101 Oral Capsules
  Intervention: Drug: APL-101 Oral Capsules
• Experimental: Basket of tumor types MET amplification except for primary CNS tumors
  Cohort C: APL-101 Oral Capsules
  Intervention: Drug: APL-101 Oral Capsules
• Experimental: NSCLC MET amplification and EGFR wild-type
  Cohort C-1: APL-101 Oral Capsules
  Intervention: Drug: 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
  Intervention: Drug: APL-101 Oral Capsules
• Experimental: Basket of solid tumor with MET gene fusions except for primary CNS tumors
  Cohort D: APL-101 Oral Capsules
  Intervention: Drug: APL-101 Oral Capsules
• Experimental: Primary CNS tumors with MET alterations
  Cohort E: APL-101 Oral Capsules
  Intervention: Drug: 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
  Intervention: Drug: APL-101 Oral Capsules

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: October 19, 2023): 497
• Original Estimated Enrollment (submitted: June 1, 2017): 68
• Estimated Study Completion Date: November 30, 2026
• Estimated Primary Completion Date: March 30, 2026 (Final data collection date for primary outcome measure)

Eligibility Criteria

Major Inclusion Criteria:

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 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Emma (Xiaoning) Cai; 6502094055; clinops@apollomicsinc.com

• Listed Location Countries: Australia, Canada, Finland, France, Hungary, Italy, Puerto Rico, Russian Federation, Singapore, Spain, Taiwan, United Kingdom, United States
• Removed Location Countries: Hong Kong, Ukraine

Administrative Information

• NCT Number: NCT03175224
• Other Study ID Numbers: APL-101-01
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Apollomics Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Apollomics Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Chair: Peony Yu; Apollomics Inc.

• PRS Account: Apollomics Inc.
• Verification Date: October 2023