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

PHASE2RECRUITING

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).

Study details:

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.

Eligibility criteria

Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.

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
  3. 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
  4. Cohort B / Exon 14 NSCLC MET inhibitor experienced: ENROLLMENT COMPLETED
  5. 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
  6. 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
  7. 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
  8. 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
  9. 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
  10. 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
  11. Treated or untreated asymptomatic parenchymal CNS disease or leptomeningeal disease is allowed.
  12. Presence of ≥1 measurable lesion (scan done ≤28 days of C1D1) to serve as target lesion according to relevant criteria
  13. ECOG performance status of 0-1. For subjects with primary CNS tumors, KPS score ≥70.
  14. Acceptable organ function
  15. 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.
  16. Adequate cardiac function
  17. 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
  18. No planned major surgery within 4 weeks of first dose of APL-101
  19. Expected survival (life expectancy) ≥ 3 months from C1D1
  20. 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.

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: Carcinoma of the skin without melanomatous features, Curatively treated cervical carcinoma in situ, 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.

Eligibility

Age eligible for study : NA

Healthy volunteers accepted : No

Gender eligible for study: ALL

Things to know

Study dates

Study start:

Primary completion:

Study completion finish:

study type

Study type

TREATMENT

phase

Phase

    PHASE2

trial

Study ID

NCT03175224

Intervention or treatment

DRUG: APL-101 Oral Capsules

Conditions

  • 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

  • Condition: Solid Tumors, Advanced Cancer and more

  • DRUG: APL-101 Oral Capsules

  • Melbourne, Australia

  • Sponsor: Apollomics Inc.

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Are you running this trial?

If you're a clinic or sponsor, you can claim this study

Research sites nearby

Closest Location:

St Vincents Hospital Melbourne

Select from list below to view details:

  • St Vincents Hospital Melbourne

    Melbourne, Australia

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Who is running the clinical trial?

AI

Apollomics Inc.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Participant Group/ArmIntervention/Treatment
EXPERIMENTAL: NSCLC Exon 14 Skip Treatment Naive
  • Cohort A-1: APL-101 Oral Capsules
Drug: APL-101 Oral Capsules
    EXPERIMENTAL: NSCLC Exon 14 Skip Previously Treated
    • Cohort A-2: APL-101 Oral Capsules
    Drug: APL-101 Oral Capsules
      EXPERIMENTAL: NSCLC Exon 14 MET Inhibitor Experienced
      • Cohort B: APL-101 Oral Capsules
      Drug: APL-101 Oral Capsules
        EXPERIMENTAL: Basket of tumor types MET amplification except for primary CNS tumors
        • Cohort C: APL-101 Oral Capsules
        Drug: APL-101 Oral Capsules
          EXPERIMENTAL: NSCLC MET amplification and EGFR wild-type
          • Cohort C-1: APL-101 Oral Capsules
          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
            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
              Drug: APL-101 Oral Capsules
                EXPERIMENTAL: Primary CNS tumors with MET alterations
                • Cohort E: APL-101 Oral Capsules
                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
                  Drug: APL-101 Oral Capsules

                    What is the study measuring?

                    Primary Outcome

                    MeasureDescriptionTime Frame
                    Objective response rate (ORR = CR + PR) per IRC committee (BIRC) based on RECIST v1.1 (or relevant criteria per tumor type)Anti-tumor activity per RECIST v1.1, RANO criteria for CNS tumors, or relevant evaluation criteria per tumor type.From time of informed consent signature through completion of treatment (1 cycle = 28 days) or progression

                    Secondary Outcome

                    MeasureDescriptionTime Frame
                    Median duration of response (DOR) per IRC.DOR per RECIST v1.1 criteria, RANO criteria for CNS tumors, or relevant evaluation criteria per tumor type.Approximately 2 years
                    ORR per investigator assessment based on RECIST v1.1.ORR per RECIST v1.1 or relevant evaluation criteria per tumor type.Approximately 2 years
                    Median DOR per investigator assessment.DOR per RECIST v1.1, RANO criteria for CNS tumors, or relevant evaluation criteria per tumor type.Approximately 2 years
                    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).Benefit rate per RECIST v1.1, RANO criteria for CNS tumors, or relevant evaluation criteria per tumor type.Approximately 2 years
                    Median time to progression (TTP).TTP per RECIST v1.1 or relevant evaluation criteria per tumor type.Approximately 2 years
                    Progression Free Survival (PFS) and overall survival (OS) at 6, 12, 18 and 24 monthsPFS and OS per RECIST v1.1 or relevant evaluation criteria per tumor type.Approximately 3 years
                    Are you running this trial?If you're a clinic or sponsor, you can claim this study.
                    Claim this trial

                    References

                    Clinical Trials Gov: APL-101 Study of Subjects With NSCLC With c-Met EXON 14 Skip Mutations and c-Met Dysregulation Advanced Solid Tumors

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