Neoplasms

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All Conditions

Neoplasm Metastasis

Antineoplastic Agents

Antirheumatic Agents

Dermatologic Agents

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All Drugs and Chemicals

Methotrexate

Tepotinib

Tepotinib 500mg (2 tablets of 250mg) per day D1-21 orally, once daily

Ki Hyeong Lee, M.D.

Eun Joo Kang, M.D.

Soon Il Lee

Yu Jeong Kim

Yun Ji Choe

The aim of this study is to understand efficacy of tepotinib in patients with solid cancers harbouring c-MET amplification or exon 14 mutation who progressed after standard treatment for metastatic disease.

This study is a basket trial with two strata(NSCLC and other cancer). If MET exon 14 skipping mutation or MET amplification(copy number gain ≥6.0 ) is detected by NGS method, then confirmation of genetic findings by Molecular Steering Committee will be followed. Patient can participate in this trial after confirmation of genetic analysis and reviewing other inclusion/exclusion criteria.

Experimental: Arm 1_NSCLC Patients with non-small cell lung cancer (NSCLC) harboring MET alteration Experimental: Arm 2_Other solid tumors Solid tumors excluding NSCLC harboring MET alteration

Tepotinib in Solid Tumors Harboring MET Alterations

A Phase II Study of Tepotinib in Patients With Solid Cancers Harboring c-MET Amplification or Exon 14 Mutation Who Progressed After Standard Treatment for Advanced/Metastatic Disease

Objective response will be determined according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as assessed by investigator.

Objective response is defined as either a confirmed complete response (CR) or partial response (PR) from first administration of trial treatment to first observation of progressive disease (PD). CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30 percent (%) reduction from baseline in the sum of the longest diameter (SLD) of all lesions. PD is defined as at least a 20% increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.

Progression free survival as assessed by investigators is defined as the time (in months) from the first administration of trial treatment to the date of the first documentation of PD (based on independent review) or death due to any cause within 84 days of the last tumor assessment, whichever occurs first

Objective disease control is defined as either a confirmed CR or PR, or stable disease (SD) lasting at least 12 weeks (84 days) as assessed by investigator. CR: Disappearance of all evidence of target and non-target lesions.

Overall survival is defined as the time (in months) from first trial treatment administration to the date of death.

This outcome measure will be presented as the percentage of subjects with any adverse event (AE). Percentages are calculated using total number of subjects per treatment cohort as the denominator.

Merck KGaA, Darmstadt, Germany

Chungbuk National University Hospital

Respiratory Tract (Lung and Bronchial) Diseases

Rare Diseases

Lung Neoplasms

Carcinoma, Non-Small-Cell Lung

Carcinoma

Adenocarcinoma

Adenocarcinoma of Lung

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Lung Adenocarcinoma

Tablet for oral use, dose Up to 400mg, twice daily

Capmatinib

MAP requests are initiated by a licensed physician.https:// www.novart is.com/healthcare-professionals/managed-access-programs

Novartis Pharmaceuticals

The purpose of this Managed Access Program (MAP) Cohort Treatment Plan is to provide guidance to the Physician for the treatment and monitoring of patients in the Cohort MAP.

The Physician should follow the suggested treatment guidelines. Furthermore, the Physician must comply with the MAP Agreement Letter and applicable local laws and regulations.

Prior to inclusion of a patient in the Cohort, the requesting Physician must submit a request for access to the product in GEMS (Grants, External Requests and Managed Access System) accessible through https://www.novartis.com/our-focus/healthcare-professionals/managedaccess- programs providing the rationale for the request and relevant medical history of the patient. The request is then assessed against the MAP and Cohort inclusion/exclusion criteria by the medical team experienced with the product and indication. Upon the required approvals, the patient is included in the Cohort.

Treatment Plan CINC280A02001M to Provide Access to Capmatinib, for MET Exon 14 Skipping Non-Small Cell Lung Cancer (NSCLC)

Managed Access Program (MAP) Cohort Treatment Plan CINC280A02001M to Provide Access to Capmatinib, for MET Exon 14 Skipping Non-Small Cell Lung Cancer (NSCLC)

Patients who fulfill eligibility criteria will be entered into the trial to receive capmatinib.

After the screening procedures confirm participation in the research study. Participants will receive capmatinib PO BID, 21-day cycles

Capmatinib (INC280)

Rebecca S. Heist, MD

This research study is studying capmatinib as a treatment for advanced non-small cell lung cancer with MET exon 14 skipping, where the participant has already received prior therapy with a MET inhibitor.

This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational intervention to learn whether the intervention works in treating a specific disease. "Investigational" means that the intervention is being studied.

The FDA (the U.S. Food and Drug Administration) has not approved Capmatinib as a treatment for any disease.

In this research study, the investigators are using the study drug called Capmatinib. Capmatinib is a specific blocker of the cMET protein. This protein acts as a trigger to start a series of events in your cells in what is known as the C-Met pathway. Patients with MET exon 14 skipping have activation of the MET pathway. By blocking MET, Capmatinib may slow or stop the growth and/or survival of cancer cells. Capmatinib is not yet FDA approved for the treatment of people with this type of cancer. It is not known if capmatinib will be effective in people who have previously had other drugs that block the cMET pathway. This study will help us understand how capmatinib works in the body and what capmatinib does to cancer. Any potential harmful effects of capmatinib will also be studied.

A Study of Capmatinib (INC280) in NSCLC Patients With MET Exon 14 Alterations Who Have Received Prior MET Inhibitor

A Phase 2 Study of Capmatinib (INC280) in NSCLC Patients With MET Exon 14 Alterations Who Have Received Prior MET Inhibitor

Objective response rate (ORR) is defined as the percentage of patients with a complete response or partial response to treatment according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Complete response (CR) is the disappearance of all target lesions. Partial response (PR) is a greater than or equal to 30% decrease in the sum of the longest diameter of target lesions. ORR = CR + PR.

Progression-Free Survival (PFS) is defined as the time from registration to the earlier of progression or death due to any cause. Participants alive without disease progression are censored at date of last disease evaluation. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

Disease control rate (DCR) will be defined as the percentage of participants with complete response, partial response, and stable disease at 12 weeks by Response Evaluation Criteria In Solid Tumors (RECIST) v1.1. Complete Response (CR) is the disappearance of all target lesions. Partial Response (PR) is a greater than or equal to 30% decrease in the sum of the longest diameter of target lesions. Stable Disease (SD) is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for Progressive Disease, taking as reference the smallest sum diameters while on study. Progressive Disease (PD) is a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. DCR = CR + PR + SD.

Intracranial response rate (IRR) will be calculated based on response assessments in the brain for patients with measurable CNS disease at baseline by RECIST v 1.1 criteria. IRR is defined as the percentage of patients with a confirmed intracranial complete response (CR) or partial response (CR) at week 12. CR is the disappearance of all target lesions and PR is a greater than or equal to 30% decrease in the sum of the longest diameter of target lesions. IRR = CR + PR.

Duration of response (DOR) will be calculated from the time of first assessment of complete response (CR) or partial response (PR) per RECIST 1.1 until the first occurrence of progressive disease (PD) or death. CR is the disappearance of all target lesions. PR is a greater than or equal to 30% decrease in the sum of the longest diameter of target lesions. PD is a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

Overall Survival (OS) is defined as the time from registration to death due to any cause, or censored at date last known alive. OS time for patients who are alive at the end of the study or are lost to follow up will be censored at the time of last contact. OS will be estimated using the Kaplan-Meier method.

Novartis

Massachusetts General Hospital

Principal Investigator

Patients who fulfill eligibility criteria will be entered into the trial to receive capmatinib.

After the screening procedures confirm participation in the research study. Participants will receive capmatinib PO BID, 21-day cycles

Capmatinib (INC280): treatment with Capmatinib (INC280)

Age, Customized

Sex: Female, Male

Race (NIH/OMB)

Never

Former

Current

Smoking History

Squamous

Sarcomatoid or poorly differentiated carcinoma

Tumor Histology

Amplification

Exon 14 skipping

MET alteration

Previous Chemotherapy

Previous Immunotherapy

3 or more

Number of previous lines of therapy

Number of previous MET-targeted therapies

Rebecca Suk Heist, MD

Objective Response Rate

Progression Free Survival

Disease Control Rate

Only 4 out of 20 participants had measurable brain metastases.

Intracranial Response Rate

Only 2 of 22 participants had complete response (CR) or partial response (PR) per RECIST 1.1, thus they were the only ones analyzed for DOR.

Duration of Response

Overall Survival

Grade 3

Grade 4

Grade 5

Number of Participants With Treatment-related Adverse Events by Grade

Overall Study

Micronutrients

Hematinics

Vitamins

Amino Acids

Carboplatin

Etoposide

Osimertinib

Pemetrexed

Cisplatin

Durvalumab

Etoposide phosphate

Alectinib

Gefitinib

Necitumumab

Enzyme Inhibitors

Folic Acid

Vitamin B Complex

Folic Acid Antagonists

Antineoplastic Agents, Immunological

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Folinic Acid

Folate

Vitamin B9

Tyrosine

The patients in this group will receive osimertinib taken in combination with savolitinib

The patients in this group will receive osimertinib taken in combination with gefitinib

The patients in this group will receive osimertinib taken in combination with necitumumab

The patients in this group will receive platinum-containing doublet (carboplatin + pemetrexed) taken in combination with durvalumab.

Patients in this group will not receive study treatment but receive further anticancer care (Standard of Care therapy or other experimental therapies) or supportive care, as clinically indicated, in accordance with local practice.

With Group C, the aim is to understand the clinical course and/or outcome for the overall clinical population after progression on first-line monotherapy with osimertinib.

The patients in this group will receive osimertinib taken in combination with alectinib

The patients in this group will receive osimertinib taken in combination with selpercatinib

The patients in this group will receive platinum-containing doublet (etoposide + carboplatin or cisplatin) taken in combination with durvalumab.

The patients in this group will receive Osimertinib plus platinum-containing doublet (pemetrexed + carboplatin or cisplatin).

The patients in this group will receive osimertinib taken in combination with selumetinib

The patients in this group will receive osimertinib taken in combination with datopotamab deruxtecan.

Osimertinib given orally at 80 mg once daily

Savolitinib will be given orally at 300 mg or 600mg once daily

Savolitinib

Gefitinib given orally at 250 mg once daily

Necitumumab given IV at 800 mg on Day 1 and Day 8 of every 3-week cycle

Durvalumab given IV at 1500 mg on Day 1 of every cycle

Carboplatin given IV on Day 1 of every 21-day cycle for up to 6 cycles

Pemetrexed given IV at 500 mg/m2 body BSA on Day 1 of every cycle

Alectinib given orally at 600mg twice daily and for Japanese patients at 300mg twice daily.

Selpercatinib given orally at 160mg twice daily

Selpercatinib

Selumetinib given orally at 75 mg twice daily for 4 days, followed by 3 days off treatment

Selumetinib

Etoposide 80-100 mg/m2 given IV on day 1, 2 and 3 of every 21-day cycle for up to 4 cycles.

Cisplatin 75-80 mg/m2 given IV on days 1 of each cycle

Datopotamab deruxtecan given IV at 4 or 6 mg/kg on Day 1 of every 3-week cycle.

Datopotamab deruxtecan

Helena A Yu, MD

Phase 2 Platform Study in Patients with Advanced Non-Small Lung Cancer who progressed on First-Line Osimertinib Therapy. This study is modular in design, allowing evaluation of the efficacy, safety and tolerability of multiple study treatments.

This is an open-label, multicentre, multi-drug, biomarker-directed Phase 2 platform study in patients with advanced non-small cell lung cancer (NSCLC) harbouring an epidermal growth factor receptor (EGFR)-sensitizing mutation whose disease has progressed on first-line monotherapy with osimertinib.Treatment options for these patients are limited. Novel treatments for these patients are urgently required.

This study is modular in design, allowing evaluation of the efficacy, safety and tolerability of multiple study treatments.

Phase 2 platform study in patients with advanced Non-Small Lung Cancer harbouring an epidermal growth factor receptor (EGFR)-sensitizing mutation with evidence of radiological progression following first-Line osimertinib therapy. This study is modular in design, allowing evaluation of the efficacy, safety and tolerability of multiple study treatments. The study will be conducted in three groups (Groups A, B and C). Patient allocation to a study treatment within each group will be based on tumour molecular profile. Biomarker positive patients or patients with histologically identifiable neuroendocrine transformation to small cell lung cancer (SCLC) or large cell neuroendocrine carcinoma (NEC) will be allocated to a biomarker-matched study treatment in Group A, patients without a biomarker will be allocated to a study treatment in Group B and patients with a biomarker amenable to therapies not currently available in ORCHARD will be allocated to Group C.

Phase 2 Platform Study in Patients With Advanced Non-Small Lung Cancer Who Progressed on First-Line Osimertinib Therapy (ORCHARD)

A Biomarker-directed Phase 2 Platform Study in Patients With Advanced Non-Small Lung Cancer Whose Disease Has Progressed on First-Line Osimertinib Therapy.

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

The percentage of patients with a confirmed investigator-assessed complete or partial response according to Response Evaluation Criteria In Solid Tumours (RECIST) 1.1. Patients will be followed up every 6 weeks (±1 week) for the first 24 weeks and every 9 weeks thereafter until RECIST 1.1 defined disease progression or cessation of study treatment (if treating beyond progression).

The time from first dose until the date of objective disease progression or death (by any cause in the absence of progression). Patients will be followed up every 6 weeks (±1 week) for the first 24 weeks and every 9 weeks thereafter until RECIST (Response Evaluation Criteria In Solid Tumours)1.1 defined disease progression or cessation of study treatment (if treating beyond progression).

The time from the date of first response until date of disease progression or death in the absence of disease progression. Patients will be followed up every 6 weeks (±1 week) for the first 24 weeks and every 9 weeks thereafter until RECIST 1.1 defined disease progression or cessation of study treatment (if treating beyond progression).

The time from the date of the first dose of study treatment until death due to any cause.

Blood samples will be collected at various timepoints to evaluate the sparse pharmacokinetics of study therapeutic agents.

Blood samples will be collected at various timepoints to evaluate the serial pharmacokinetics of study therapeutic agents

To evaluate safety and tolerability of each study treatment

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Tepotinib in Solid Tumors Harboring MET Alterations	NCT04647838	Solid Tumor MET Exon 14 Ski... MET Amplificati...	Tepotinib	19 Years -	Chungbuk National University Hospital
Treatment Plan CINC280A02001M to Provide Access to Capmatinib, for MET Exon 14 Skipping Non-Small Cell Lung Cancer (NSCLC)	NCT04741789	Carcinoma, Non-... Non-Small Cell ... Non-Small-Cell ... Nonsmall Cell L...	Capmatinib	18 Years - 99 Years	Novartis
Treatment Plan CINC280A02001M to Provide Access to Capmatinib, for MET Exon 14 Skipping Non-Small Cell Lung Cancer (NSCLC)	NCT04741789	Carcinoma, Non-... Non-Small Cell ... Non-Small-Cell ... Nonsmall Cell L...	Capmatinib	18 Years - 99 Years	Novartis
A Study of Capmatinib (INC280) in NSCLC Patients With MET Exon 14 Alterations Who Have Received Prior MET Inhibitor	NCT02750215	Malignant Non-s...	Capmatinib (INC...	18 Years -	Massachusetts General Hospital
Phase 2 Platform Study in Patients With Advanced Non-Small Lung Cancer Who Progressed on First-Line Osimertinib Therapy (ORCHARD)	NCT03944772	Non-Small Cell ...	Osimertinib Savolitinib Gefitinib Necitumumab Durvalumab Carboplatin Pemetrexed Alectinib Selpercatinib Selumetinib Etoposide Cisplatin Datopotamab der...	18 Years - 130 Years	AstraZeneca

Spots Global Cancer Trial Database for met exon 14 skipping