APL-101 (Bozitinib) for Non-small cell lung cancer | Central nervous system neoplasm | Advanced solid tumour

Inclusion criteria

• {"criterion_text":"- 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.\n- 10. For all prior anticancer treatment, including radiotherapy, chemotherapy or targeted agents (except EGFR-I for Cohort C2) 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. Palliative radiotherapy to non-target lesions should be completed within 2 weeks prior to APL-101 administration. Subjects with glioblastoma (GBM) on Optune therapy may be allowed if the following criteria are met: • Must agree to switch off Optune at least 3 days prior to C1D1 and during the study. • All AEs associated with Optune use must be resolved to Grade ≤ 1 at least 3 days prior to C1D1. • An MRI/CT scan is performed after discontinuation of Optune.\n- 11. Adequate cardiac function (≤ New York Heart Association [NYHA] class II) or normal cardiac function with left ventricular ejection fraction (LVEF) ≥ 50% at screening.\n- 12. Women of child-bearing potential (WOCBP) must have a negative serum or B-human chorionic gonadotropin (B-hCG) at screening or evidence of surgical sterility or evidence of post-menopausal 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.\n- 13. 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.\n- 14. Resolution of all chemotherapy, radiotherapy or surgery-related AEs to Grade ≤ 1, except for alopecia. Subjects who experienced significant complications with prior immuno-oncology (IO) therapy or EGFR-Inhibitor therapy during or after treatment; e.g., pneumonitis/interstitial lung disease [ILD], Grade 3 or higher LFT abnormalities, or QT abnormalities will not qualify to participate.\n- 15. No planned major surgery within 4 weeks of first dose of APL-101.\n- 16. Willing and able to participate in all required evaluations and procedures in this study.\n- 17. Expected survival (life expectancy) ≥ 3 months from C1D1.\n- 2. Men and women 18 years of age or older.\n- 3. For Phase 1, histologically and / or cytologically confirmed unresectable or metastatic solid malignancy, refractory to standard therapies with no more than three prior lines of therapy.\n- 4. For Phase 2, nine (9) cohorts will be enrolled: 4a. Cohort A-1 (all countries except Finland): Exon 14 NSCLC – MET inhibitor naïve (1L). 4b. Cohort A-2: Exon 14 NSCLC – MET inhibitor naïve 4c. Cohort B: Exon 14 NSCLC – MET inhibitor experienced (Enrolment Completed) 4d. Cohort C: MET amplification basket tumor types excluding primary CNS tumors 4e. Cohort C-1: MET amplification and wild-type EGFR NSCLC 4f. Cohort C-2: EGFR positive NSCLC with acquired MET amplification (APL-101 Add-on Therapy Cohort) 4g. Cohort D: MET fusion basket tumor types excluding primary CNS tumors 4h. Cohort E: Primary CNS tumors with MET alterations 4i. Cohort F: Basket tumor types harboring wild-type MET with over-expression of HGF and MET For further details, please refer to the protocol.\n- 5. In Phase 2, 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 further details, please refer to the protocol.\n- 6. Treated or untreated asymptomatic parenchymal CNS disease or leptomeningeal disease is allowed.\n- 7. Presence of ≥1 measurable lesion (scan done ≤28 days of C1D1) to serve as target lesion according to relevant criteria (RECIST v1.1, RANO for CNS tumors, or other relevant criteria per tumor type) prospectively confirmed by the Independent Review Committee (IRC)\n- 8. ECOG performance status of 0–1. For subjects with primary CNS tumors, KPS score ≥70.\n- 9. 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."}

Exclusion criteria

• {"criterion_text":"- 1. Hypersensitivity to APL-101, excipients of the drug product, or other components of the study treatment regimen.\n- 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).\n- 11. Women who are breastfeeding.\n- 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: a. Carcinoma of the skin without melanomatous features. b. Curatively treated cervical carcinoma in situ. c. 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.\n- 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.\n- 14. Subjects with active COVID-19 infection.\n- 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.\n- 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.\n- 3. Use or intended use of any other investigational product, including herbal medications, through Study Treatment Termination.\n- 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.\n- 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.\n- 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. Chronic controlled atrial fibrillation is not excluded.\n- 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.\n- 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.\n- 9. Unable to swallow orally administered medication whole."}

Primary endpoints

• {"endpoint_text":"- 1. Phase 1 (Completed): Estimate the MTD and the incidence of DLTs in Cycle 1, sustained Grade 2 AEs, dose reductions, dose interruptions and any occurrences of delayed toxicities and other AEs to determine the RP2D dosing of APL-101","definition_or_measurement_approach":"Estimate MTD and incidence of DLTs in Cycle 1; capture sustained Grade 2 adverse events, dose reductions, dose interruptions, delayed toxicities and other adverse events to determine RP2D."}
• {"endpoint_text":"- 2. Phase 2: Objective response rate (ORR; defined as complete response [CR] + partial response [PR]) per independent review committee (IRC) based on RECIST v1.1 criteria, RANO criteria for CNS tumors, or other relevant criteria per tumor type.","definition_or_measurement_approach":"ORR defined as CR + PR determined by an Independent Review Committee using RECIST v1.1 for systemic tumors, RANO for CNS tumours, or other tumor-type relevant criteria."}

Secondary endpoints

• {"endpoint_text":"- 1. Median duration of response (DOR) per IRC.","definition_or_measurement_approach":"Median DOR as assessed by IRC."}
• {"endpoint_text":"- 2. ORR per investigator assessment based on RECIST v1.1 criteria, RANO criteria for CNS tumors, or other relevant criteria per tumor type.","definition_or_measurement_approach":"ORR (CR+PR) by investigator assessment using RECIST v1.1, RANO for CNS tumours, or other relevant tumor-specific criteria."}
• {"endpoint_text":"- 3. Median DOR per investigator assessment.","definition_or_measurement_approach":"Median DOR as assessed by investigator."}
• {"endpoint_text":"- 4. Antitumor activity by clinical benefit rate (CR + PR + SD ≥ 4 cycles) based on RECIST v1.1 criteria, RANO criteria for CNS tumors, or other relevant criteria per tumor type.","definition_or_measurement_approach":"Clinical benefit rate defined as CR + PR + stable disease for ≥4 cycles assessed per RECIST v1.1, RANO or other tumor-specific criteria."}
• {"endpoint_text":"- 5. Median time to progression (TTP).","definition_or_measurement_approach":"Median time from baseline to disease progression (TTP)."}
• {"endpoint_text":"- 6. Progression-free survival (PFS) and overall survival (OS) at 6, 12, 18, and 24 months.","definition_or_measurement_approach":"PFS and OS rates evaluated at 6, 12, 18 and 24 months."}

France

Earliest CTIS Part Ii Submission Date

16-07-2024

Latest Decision Or Authorization Date

10-09-2024

Processing Time Days

56

Number Of Sites

8

Number Of Participants

100

Hungary

Earliest CTIS Part Ii Submission Date

16-07-2024

Latest Decision Or Authorization Date

23-07-2024

Processing Time Days

7

Number Of Sites

2

Number Of Participants

6

Italy

Earliest CTIS Part Ii Submission Date

16-07-2024

Latest Decision Or Authorization Date

29-07-2024

Processing Time Days

13

Number Of Sites

8

Number Of Participants

50

Spain

Earliest CTIS Part Ii Submission Date

16-07-2024

Latest Decision Or Authorization Date

22-07-2024

Processing Time Days

6

Number Of Sites

8

Number Of Participants

115

Primary sponsor

Full Name

Apollomics Inc.

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Contract research organisations

Name

Medidata Solutions Inc.

Responsibilities

sponsorDuties codes: 7

Name

Labcorp Central Laboratory Services SARL

Responsibilities

central laboratory services (code 4)

Name

Caris Mpi Inc.

Responsibilities

laboratory/biomarker support (code 4)

Name

Andersonbrecon Inc.

Responsibilities

IP labeling/packaging/storage/distribution

Name

Q Square Business Intelligence Corp.

Responsibilities

data/biostatistics or business intelligence (code 6)

Third parties

• {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"sponsorDuties codes: 7","organisation_type":"Non-Pharmaceutical company"}
• {"country":"France","full_name":"Novasco","duties_or_roles":"patient stipend/travel (code 15)","organisation_type":"Pharmaceutical company"}
• {"country":"Spain","full_name":"Taxi Travel Ticket S.L.","duties_or_roles":"patient stipend/travel (code 15)","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Q Square Business Intelligence Corp.","duties_or_roles":"sponsorDuties code: 6","organisation_type":"Pharmaceutical company"}
• {"country":"Switzerland","full_name":"Labcorp Central Laboratory Services SARL","duties_or_roles":"central laboratory services (code 4)","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Caris Mpi Inc.","duties_or_roles":"laboratory/biomarker support (code 4)","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Andersonbrecon Inc.","duties_or_roles":"IP labeling/packaging/storage/distribution (code 15)","organisation_type":"Pharmaceutical company"}
• {"country":"Hungary","full_name":"Trialbooster Kft.","duties_or_roles":"patient stipend/travel (code 15)","organisation_type":"Pharmaceutical company"}
• {"country":"Spain","full_name":"Sofpromed Investigacion Clinica S.L.","duties_or_roles":"multiple site duties/codes: 1,12,2,5","organisation_type":"Hospital/Clinic/Other health care facility"}