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METalmark - Investigation-specific Appendix 1 to Master Protocol PLATFORMPANSC2001 (KALEIDOSCOPE) A Phase 1/2 Study Evaluating the Safety and Efficacy of Amivantamab and Capmatinib Combination Therapy in Unresectable Metastatic Non-small Cell Lung Cancer - 61186372PANSC2001

Studio Clinico

Patologia: Neoplasie del polmone

Osservazionale-Sperimentale: Sperimentale

Monocentrico-Multicentrico: Multicentrico

Randomizzato: No

Fase di studio: 1, II

Richiesta mandatoria di tessuto: 

Linee di trattamento: Prima linea, Seconda linea, Terza/N linea

Criteri di inclusione: 

1. ≥18 years of age (or the legal age of consent in the jurisdiction in which the study is taking place) at the time of informed consent.
2. Previously diagnosed with histologically or cytologically confirmed unresectable Stage IV (metastatic) NSCLC (any histology).
3.1. For Phase 1 – Combination Dose Selection:
Metastatic NSCLC progressed on or after standard of care systemic anti-cancer therapy and is declining other systemic treatment options, if any:
    - Participants must have had disease progression on or have intolerance to prior platinum based chemotherapy and an anti-PD-(L)1 antibody given concurrently or sequentially
OR
   - Participants with targetable genomic aberrations must have had prior disease progression on or have intolerance to appropriate targeted therapies as per local standard of care
Participants who may have received prior therapy with amivantamab and/or capmatinib as long as discontinuation was not due to toxicity.
4.1. For Phase 2 – Expansion:
    - Cohort 1A: MET exon 14 skipping mutation (without prior therapy for metastatic disease)
    - Metastatic NSCLC previously characterized as MET exon 14 skipping mutation positive AND lacking EGFR and ALK mutation, by a local test using a CLIA certified laboratory or an accredited laboratorya
    - Participant must not have received systemic anti-cancer therapy for metastatic NSCLC. Neo-adjuvant and adjuvant therapies for earlier stage disease are allowed if relapse occurred >12 months from end of neoadjuvant or adjuvant systemic therapy
    - Adequate tumor tissue sample must be submitted to the sponsor
    - Cohort 1B: MET exon 14 skipping mutation (prior therapy)
    - Metastatic NSCLC previously characterized as MET exon 14 skipping mutation positive AND lacking EGFR and ALK mutation, by a local test using a CLIA certified laboratory or an accredited laboratorya
    - Progression of metastatic disease on at least 1 but no more than 3 lines of prior systemic anti-cancer therapy, which may include MET TKI or chemotherapy as per local standard of care, but may not include prior amivantamab
    - Participants who have received prior amivantamab will be excluded
    - Adequate tumor tissue sample must be submitted to the sponsor
    - Cohort 1C: MET amplification (prior therapy)
    - Metastatic NSCLC previously characterized as having MET amplification (≥5 copy number of MET) AND lacking EGFR and ALK mutation, by a local test using a CLIA certified laboratory or an accredited laboratorya
    - Progression of metastatic disease on at least 1 but no more than 3 prior lines of standard of care therapy for metastatic disease
    - Participants who have received prior amivantamab will be excluded
    - Submission of adequate archival or fresh tumor tissue, obtained following metastatic NSCLC diagnosis and after disease progression on the last systemic therapy is required as specified in Section 8.5
    a. Molecular testing for EGFR mutation, ALK rearrangement-negative, and MET exon 14 skipping mutation must be performed in accordance with local guidelines using an FDA-approved or other validated test in a CLIA certified laboratory (sites in US) or an accredited laboratory (sites outside the US) in accordance with site standard of care. In the EU, the test must be CE Marked or an in-house test from health institutions in the EU in accordance with Article 5(5) of the In vitro Diagnostic Regulation
(IVDR 2071/746), as amended. Note that a copy of the test report documenting the molecular testing result must be included in the patient records and must be submitted to the sponsor during the screening Phase.
5. At least 1 measurable lesion, according to RECIST v1.1. Must not have been previously irradiated. May be used for the screening biopsy provided baseline tumor assessment scans are performed ≥7 days after the biopsy.
Brain and Central Nervous System Metastases
6. May have: definitively, locally treated brain metastases that are clinically stable and asymptomatic for >2 weeks and who are off or receiving low-dose corticosteroid treatment (≤10 mg prednisone or equivalent) for at least 2 weeks prior to start of study treatment.
Prior Malignancies
7. May have a prior malignancy (other than the disease under study) the natural history or treatment of which is unlikely to interfere with any study endpoints of safety or the efficacy of the study treatment(s) (see Appendix 7). Must be reviewed and agreed to with medical monitor.
Performance Status
8. Have an ECOG performance status of 0 or 1 (see Appendix 6 in Master protocol PLATFORMPANCS2001).
9. Have an estimated glomerular filtration rate (eGFR) >30 mL/min as measured or calculated by Modification of Diet in Renal Disease (MDRD) 4-variable formula (see Appendix 10).
Hepatic Function
10. Participants with no underlying hepatic metastases are eligible if they have:
    - Albumin >3 g/dL, AST <3 x ULN, Total bilirubin <1.5 x ULN (isolated total bilirubin ≥1.5 x ULN with conjugated [direct]
    - bilirubin <1.5 x ULN is allowed for those participants with known Gilbert’s syndrome).
11. Participants with known hepatic metastases are eligible if they have:
    - Albumin >3 g/dL, AST <5 x ULN, ALT <5 x ULN, Total bilirubin <3 x ULN (isolated total bilirubin ≥3 x ULN with conjugated [direct] bilirubin <1.5 x ULN is allowed for those participants with known Gilbert’s syndrome)
12. Participant must have adequate organ and bone marrow function as follows, without history of red blood cell transfusion, platelet transfusion, or use of granulocyte colony-stimulating factor (G-CSF) within 7 days prior to the date of the laboratory test.
    - Hemoglobin ≥8 g/dL
    - Absolute neutrophil count (ANC) ≥1.0x109/L
    - Platelets ≥50x109 13. Human immunodeficiency virus (HIV)-positive participants are eligible if they meet all of the following:
    a. No detectable viral load (ie, <50 copies/mL) at screening
    b. CD4+ count >300 cells/mm3 at screening
    c. No acquired immunodeficiency syndrome (AIDS)-defining opportunistic infection within 6 months of screening
    d. Receiving highly active antiretroviral therapy (HAART). Any changes in HAART due to resistance/progression should occur at least 3 months prior to screening.
A change in HAART due to toxicity is allowed up to 4 weeks prior to screening.
Note: HAART that could interfere with study treatment is excluded (consult the sponsor for a review of medications prior to enrollment).
14. A female participant of childbearing potential must have a negative serum pregnancy test at screening and within 72 hours of the first dose of study treatment and must agree to further serum or urine pregnancy tests during the study.
15. A female participant must be either of the following (as defined in Appendix 5)
    a. Not of childbearing potential, or
    b. Of childbearing potential and practicing at least 1 highly effective method of contraception contraception throughout the study and through 3 months after the last dose of study treatment.
Note: If a female participant becomes of childbearing potential after the start of the study, the female participant must comply with (b.).
16. A female participant must agree not to be pregnant, or breast-feeding, or planning to become pregnant while enrolled in this study or within 3 months after the last dose of study treatment.
17. A female participant must agree not to donate eggs (ova, oocytes) or freeze for future use for the purposes of assisted reproduction during the study and for a period of 3 months after receiving the last dose of study treatment. Female participants should consider preservation of eggs prior to study treatment as anti-cancer treatments may impair fertility.
18. A male participant must wear a condom with or without spermicide when engaging in any activity that allows for passage of ejaculate to another person during the study and for 3 months after receiving the last dose of study treatment.
If the male participant’s partner is a female of childbearing potential, the male participant must use condom with or without spermicide (as required per local regulations) and the female partner of the male participant must also be practicing a highly effective method of contraception (see Appendix 5). A male participant who is vasectomized must still use a condom (with or without spermicide), but the partner is not required to use contraception.
19. A male participant must agree not to donate sperm for the purposes of reproduction during the study and for 3 months after receiving the last dose of study treatment. Male participants should consider preservation of sperm prior to study treatment as anti-cancer treatments may impair fertility.
20. A male participant must agree not to plan to father a child while enrolled in this study or within 3 months after the last dose of study treatment.
21. Must sign the Master ICF and an ICF specific for this ISA (or their legally acceptable representative must sign) indicating that the participant understands the purpose of, and procedures required for, the study and is willing to participate in the study.
22. Must sign a separate ICF (or their legally acceptable representative must sign) if the participant agrees to provide an optional samples for research (where local regulations permit). Refusal to give consent for the optional research samples does not exclude a participant from participation in the study.
23. Be willing and able to adhere to the lifestyle restrictions specified in this protocol.

Criteri di esclusione: 

1. History of uncontrolled illness, including but not limited to:
    a. Uncontrolled diabetes
    b. Ongoing or active infection (includes infection requiring treatment with antimicrobial therapy [participants will be required to complete antibiotics 1 week prior to starting study treatment] or diagnosed or suspected viral infection). See also inclusion criterion 13 and exclusion criterion 14 for considerations with respect to HIV and hepatitis infection, respectively.
    c. Active bleeding diathesis
    d. Impaired oxygenation requiring continuous oxygen supplementation
    e. Psychiatric illness or any other circumstances (including social circumstances) that would limit compliance with study requirements
2. Medical history of (non-infectious) ILD/pneumonitis, or has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening.
3. Known allergies, hypersensitivity, or intolerance to
    a. amivantamab excipients (refer to the IB).
    b. capmatinib or its excipients (refer to the package insert or local labeling
4. Participant has, or will have, any of the following:
    a. An invasive operative procedure with entry into a body cavity, within 4 weeks or without complete recovery before administration of the first study treatment. Thoracentesis, if needed, and percutaneous biopsy for baseline tumor tissue sample may be done less than 4 weeks prior to administration of the first study treatment, as long as the participant has adequately recovered from the procedure prior to the first dose of study treatment in the clinical judgement of the investigator.
    b. Significant traumatic injury within 3 weeks before the start of administration of the first study treatment (all wounds must be fully healed prior to Day 1). Expected major surgery while the investigational agent is being administered or within 6 months after the last dose of study treatment.
Note: Participants with planned surgical procedures to be conducted under local anesthesia may participate.
5. The participant has impairment of the gastrointestinal function that could affect absorption of capmatinib or is unable or unwilling to swallow tablets.
6. Participant has a history of clinically significant cardiovascular disease including, but not limited to the following:
    a. Diagnosis of deep vein thrombosis or pulmonary embolism within 1 month prior to administration of the first dose of study treatment, or any of the following within 6 months prior to administration of the first dose of study treatment: myocardial infarction, unstable angina, stroke, transient ischemic attack, coronary/peripheral artery bypass graft, or any acute coronary syndrome. Clinically non-significant thrombosis, such as non-obstructive catheter-associated clots, are not exclusionary.
    b. Prolonged QTc interval >480 msec or clinically significant cardiac arrhythmia or electrophysiologic disease (eg, placement of implantable cardioverter defibrillator or atrial fibrillation with uncontrolled rate).
    c. Note: Participants with cardiac pacemakers who are clinically stable are eligible
    d. Uncontrolled (persistent) hypertension: systolic blood pressure >160 mmHg; diastolic blood pressure >100 mmHg.
    e. Congestive heart failure (CHF) defined as New York Heart Association (NYHA) class III-IV or hospitalization for CHF (any NYHA class) within 6 months of administration of the first study treatment.
    f. Pericarditis/clinically significant pericardial effusion within 1 month prior to administration of the first dose of study treatment.
    g. Myocarditis.
7. Participant received thoracic radiotherapy to lung fields ≤4 weeks prior to Cycle 1 Day 1 or patients who have not recovered from radiotherapy-related toxicities. For all other anatomic sites (including radiotherapy to thoracic vertebrae and ribs), radiotherapy ≤2 weeks prior to Cycle 1 Day 1 or patients who have not recovered from radiotherapy-related toxicities.
8. Participant has
    a. (or has a history of) leptomeningeal disease (carcinomatous meningitis).
    b. spinal cord compression not definitively treated with surgery or radiation.
9. Participant has symptomatic central nervous system (CNS) metastases which are neurologically unstable or have required increasing doses of steroids >10 mg prednisone or equivalent within the 2 weeks prior to study entry to manage CNS symptoms.
10. Participant has uncontrolled tumor-related pain: Symptomatic lesions amenable topalliative radiotherapy (eg, bone metastases, or metastases causing nerve impingement)
should be treated more than 7 days prior to the administration of the first studytreatment.
11. Participant received live or live attenuated vaccine(s) within 3 months prior to screening or plans to receive such vaccines during the study. Vaccines approved or authorized for emergency use (eg, COVID-19) and non-live vaccines (eg, influenza) are allowed.
12. Participant has had prior chemotherapy, targeted cancer therapy, or treatment with an investigational anticancer agent within 2 weeks or 4 half-lives, whichever is longer, before administration of the first study treatment. For agents with long half-lives such as immunotherapy, the maximum required time since last dose is 28 days. Toxicities from previous anticancer therapies should have resolved to baseline levels or to Grade 1 or less prior to the first dose of study treatment (except for alopecia or post-radiation skin changes [any grade], Grade ≤2 peripheral neuropathy, and Grade ≤2 hypothyroidism stable on hormone replacement).
13. Participant is receiving the following medications that cannot be discontinued for at least 4 elimination half-lives as mentioned in Section 6.8.3 prior to start of treatment with capmatinib + amivantamab:
Strong/moderate inducers of CYP3A
14. Active hepatitis B or C virus infection according to local laboratory range, on all available tests for the past 6 months or other clinically active liver disease.Seropositive for hepatitis B: defined by a positive test for hepatitis B surface antigen [HbsAg]. Participants with resolved infection (ie, participants who are HbsAg negative with antibodies to total hepatitis B core antigen [anti-HBc] with or without the presence of hepatitis B surface antibody [anti-HBs]) must be screened using RT-PCR measurement of hepatitis B virus (HBV) DNA levels. Those who are RT-PCR positive will be excluded. Participants with serologic findings suggestive of HBV vaccination (anti-HBs positivity as the only serologic marker) AND a known history of prior HBV vaccination, do not need to be tested for HBV DNA by RT-PCR. (see Appendix 11).Known hepatitis C infection or positive serologic testing for hepatitis C virus (anti-HCV antibody.Positive hepatitis C antibody test result at screening or within 3 months prior to starting study treatment. NOTE: Participants with positive hepatitis C antibody due to prior resolved disease can be enrolled only if a confirmatory negative hepatitis C RNA test is obtained.
Positive hepatitis C RNA test result at screening or within 3 months prior to first dose of study treatment. NOTE: Test is optional and participants with negative hepatitis C
antibody test are not required to also undergo hepatitis C RNA testing.
15. Other clinically active liver disease of infectious origin.
16. Any condition for which, in the opinion of the investigator, participation would not be in the best interest of the participant (eg, compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments. 

Numero di pazienti previsti: 

11

Schema di trattamento: 

Amivantamab IV + Capmatinib

Trattamento sperimentale: 

Amivantamab and Capmatinib

Trattamento di controllo: 

NAP

Obiettivi primari dello studio: 

L’obiettivo primario della Fase 1 è identificare la/e dose/i di combinazione raccomandata/e della Fase 2 (Recommended Phase 2 Combination Dose, RP2CD) della terapia di combinazione con amivantamab e capmatinib nei partecipanti con NSCLC. L’obiettivo primario della Fase 2, di Espansione è valutare l’effetto antitumorale della terapia di combinazione con amivantamab e capmatinib nella mutazione di skipping dell’esone 14 di MET e nell’NSCLC con amplificazione di MET, quando somministrato alla/e RP2CD selezionata/e.

Obiettivi secondari dello studio: 

L’obiettivo secondario per entrambe le fasi è valutare ulteriormente la sicurezza e la tollerabilità della terapia di combinazione con amivantamab e capmatinib. Altri obiettivi secondari per l’Espansione della Fase 2 sono valutare ulteriormente il beneficio clinico ottenuto dalla terapia di combinazione con amivantamab e capmatinib e, solo per la Coorte 1A, valutare la qualità della vita correlata alla salute.

Note generali: 

In Italia è attiva solo la Fase II.

Data inizio arruolamento (Fase II): 22-11-2023.

 

Data di fine dell'arruolamento: 22.05.2025

Centri partecipanti

Nord Italia

Grande Ospedale Metropolitano Niguarda
Piazza Ospedale Maggiore 3 - 20162 Milano - MI

 

IRCCS Istituto Nazionale dei Tumori
Via Venezian 1 - 20133 Milano - MI

 

Istituto Oncologico Veneto IRCCS
Via Gattamelata 64 - 35128 Padova - PD

 

Ospedale S. Maria delle Croci, Ravenna
Viale Randi 5 - 48121 Ravenna - RA

 

Centro Italia

Istituto Nazionale Tumori “Regina Elena”
Via Elio Chianesi 53 - 00144 Roma - RM
NB: Arruolamento pazienti non ancora attivo

 

Sud Italia e isole

Istituto Nazionale Tumori IRCCS Fondazione Pascale
Via Mariano Semmola - 80131 Napoli - NA
NB: Arruolamento pazienti non ancora attivo

Informazioni Generali

Protocollo

Numero di iscrizione a registro: 2022-000485-18 - 2022-500729-34-00

Data di inserimento: 04.01.2024

Promotore

Janssen Research & Development, LLC

Principal Investigator ITALIA

Riferimento: Dr. Info non disponibile

Telefono: 00000

Email: nd@nd.it

Localita: nd

 

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