PALOMA-2 - Studio di fase 2, in aperto, di coorte parallela su amivantamab per via sottocutanea in regimi multipli in pazienti con tumori solidi in stadio avanzato o metastatico, compreso il tumore polmonare non a piccole cellule con mutazioni di EGFR - 61186372NSC2002

Studio Clinico

Patologia: Neoplasie del polmone

Osservazionale-Sperimentale: Sperimentale

Monocentrico-Multicentrico: Multicentrico

Randomizzato: No

Fase di studio: II

Linee di trattamento: Prima linea, Seconda linea

Criteri di inclusione: 

- Be ≥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.
- Participant must have histologically or cytologically confirmed, locally advanced or metastatic, NSCLC that is not amenable to curative therapy including surgical resection or chemoradiation;
Cohorts 1, 3, 3b, 5, 6, and 7: EGFR Exon19del or Exon 21 L858R mutation
Cohort 2, 3, 3b, and 7 only: Squamous NSCLC are excluded.
All cohorts except Cohort 4:
Participants must have at least 1 measurable lesion, according to RECIST v1.1. If the only target lesion has been previously irradiated, it must show signs of disease progression since radiation was completed. If only 1 non-irradiated measurable lesion exists, which undergoes a biopsy and is acceptable as a target lesion, the baseline tumor assessment scans should be performed at least 14 days after the biopsy.
Prior Malignancies
May have a prior or concurrent second malignancy (other than the disease under study) which natural history or treatment is unlikely to interfere with any study endpoints of safety or the efficacy of the study treatment(s) (see Appendix 12 on Allowed Recent Second or Prior Malignancies for details).
Prior Therapy Restrictions or Requirements
5.3. Cohort-specific requirements with regards to prior therapy are as follows:
Cohort 4:
Participants need to currently be on an amivantamab IV Q2W regimen (1,050 mg or 1,400 mg depending on weight) for at least 8 weeks, as part of standard of care, an expanded access program, or as a rollover from a long-term extension, without any amivantamab dose reduction. The participant must not have evidence of progressive disease during treatment on amivantamab IV or at the time of study enrollment. No washout is required between IV and SC-CF administration.
Cohort 7:
Participants must have progressed on or after the combination of amivantamab and lazertinib as the most recent line of treatment. The combination of amivantamab and lazertinib must have been administered as the first-line treatment for locally advanced or metastatic disease. No washout is required for amivantamab and lazertinib. Participants who received neoadjuvant or adjuvant treatment of any type are eligible if progression occurred at least 12 months after the last dose of such therapy and then the participant progressed on or after amivantamab and lazertinib in the locally advanced or
metastatic setting.
6.1 Toxicities from prior anticancer therapy, if any, must have resolved to CTCAE Version 5.0 Grade 1 or baseline level (except for other toxicities as indicated in inclusion criteria 8, alopecia [any grade], Grade ≤2 peripheral neuropathy, and Grade <2 hypothyroidism stable on hormone replacement).
For Cohorts 4 and 7 only:
Toxicities related to amivantamab monotherapy or in combination with lazertinib that are stable and deemed tolerable by the investigator and participant are not exclusionary.
Performance Status
7. Participant must have ECOG status of 0 or 1.
Renal, Hepatic and Hematological Function
8.3. Participant must demonstrate adequate organ and bone marrow function required for safe administration of the cohort-specific regimen, without history of red blood cell transfusion or platelet transfusion within 7 days prior to the date of the laboratory test, as follows:
Cohorts 1, 4, 5, and 6 (chemotherapy-free regimens):
a. Hemoglobin ≥9 g/dL
b. Absolute neutrophil count ≥1.5x109/L, without use of granulocyte colony stimulating factor (G-CSF) within 10 days prior to the date of the test
c. Platelets ≥75x109/L
d. ALT and AST ≤3xULN if no demonstrable liver metastases or ≤5xULN in the presence of liver metastases.
e. Total bilirubin ≤1.5xULN (participants with Gilbert’s syndrome can enroll if conjugated bilirubin is within normal limits)
f. eGFR ≥45 mL/min as measured or calculated by MDRD (Appendix 11: Formulas for Estimating Glomerular Filtration Rate Using Modified Diet in Renal Disease Formula [in mL/min])
Cohorts 2, 3, 3b and 7 (chemotherapy regimens):
a. Hemoglobin ≥10 g/dL
b. Absolute neutrophil count ≥1.5x109/L, without use of G-CSF within 10 days prior to the date of the test
c. Platelets ≥100x109/L
d. ALT and AST ≤3 xULN if no demonstrable liver metastases or ≤5xULN in the presence of liver metastases.
e. Total bilirubin ≤1.5xULN (participants with Gilbert’s syndrome can enroll if conjugated bilirubin is within normal limits)
HIV Status
9. Human immunodeficiency virus-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 AIDS-defining opportunistic infection within 6 months of screening
    d. Receiving 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).
Sex and Contraceptive/Barrier Requirements
10.1 A 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 and for 6 months after the last dose of study treatment.
11.1 A participant must be either of the following (as defined in Appendix 5: Contraceptive and Barrier Guidance)
a. Not of childbearing potential, or b. Of childbearing potential and practicing at least 1 highly effective method of contraception (details in Appendix 5: Contraceptive and Barrier Guidance) contraception throughout the study and through 6 months after the last dose of study treatment.
Note: If a participant becomes of childbearing potential after the start of the study, the participant must comply with (b).
12.1 A 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 6 months after receiving the last dose of study treatment. Participants should consider preservation of eggs prior to study treatment as anti-cancer treatments may impair fertility.
13.1 A participant must agree not to be pregnant, breast feeding, or planning to become pregnant while enrolled in this study or within 6 months after the last dose of study treatment.
14.1 A participant must wear a condom when engaging in any activity that allows for passage of ejaculate to another person during the study and for 6 months after receiving the last dose of study treatment. If the participant’s partner is a person of childbearing potential, the participant must use condoms and the partner of the participant must also be practicing a highly effective method of contraception (see Appendix 5: Contraceptive and Barrier Guidance). A vasectomized participant must still use a condom, but the partner is not required to use contraception.
15.1 A participant must agree not to donate sperm for the purposes of reproduction during the study and for 6 months after receiving the last dose of study treatment. Participants should consider preservation of sperm prior to study treatment as anti-cancer treatments may impair fertility.
Informed Consent
16.1 Must sign an ICF (or their legally acceptable representative must sign if allowed per local regulation) indicating that the participant understands the purpose of, and procedures required for, the study and is willing to participate in the study.
Note: Participants for Cohort 7, who come from Cohort 1, 5 or 6 within the PALOMA-2 study upon disease progression, must be re-consented.
17.1. Be willing and able to adhere to the lifestyle restrictions specified in this protocol.

Criteri di esclusione: 

Any potential participant who meets any of the following criteria will be excluded from participating in the study: participating in the study:
Medical Conditions
1. Participant has an 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).
    c. Active bleeding diathesis
    d. Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product, or previous significant bowel resection that
would preclude adequate absorption of study treatment
    e. Psychiatric illness or any other circumstances (including social circumstances) that would limit compliance with study requirements
    f. Any ophthalmologic condition that is clinically unstable
2. Participant has a medical history of ILD, including drug induced ILD or radiation pneumonitis
3. Participant has a history of hypersensitivity to any excipients of the investigational products to be used in their enrollment cohort
4.3. Participant has a history of clinically significant cardiovascular disease including, but not limited to:
    a. All cohorts: Diagnosis of deep vein thrombosis or pulmonary embolism within 1 month prior to the first dose of study treatment(s), or any of the following
within 6 months prior to the first dose of study treatment(s): 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 catheterassociated clots, are not exclusionary.
    b. All cohorts with regimens potentially including lazertinib: Participant has a significant genetic predisposition to venous thromboembolic events (VTE; such as Factor V Leiden).
    c. All cohorts with regimens potentially including lazertinib: Participant has a rior history of VTE and is not on appropriate therapeutic anticoagulation as per NCCN or local guidelines.
    d. Prolonged QTcF interval >480 msec or clinically significant cardiac arrhythmia or electrophysiologic disease (eg, placement of implantable cardioverter defibrillator or atrial fibrillation with uncontrolled rate).
    e. Uncontrolled (persistent) hypertension: systolic blood pressure >160 mmHg; diastolic blood pressure >100 mmHg
    f. Congestive heart failure defined as NYHA class III-IV or hospitalization for CHF (any NYHA class) [Appendix 8] within 6 months of treatment initiation at C1D1
    g. Pericarditis/clinically significant pericardial effusion
    h. Myocarditis
    i. Baseline LVEF below the institution’s lower limit of normal at screening, as assessed by echocardiogram or MUGA scan.
5. Participant had major surgery (eg, requiring general anesthesia), excluding placement of vascular access or tumor biopsy, or had significant traumatic injury within 4 weeks before signing the ICF, or will not have fully recovered from surgery, or has surgery planned during the time the participant is expected to participate in the study.
Note: Participants with planned surgical procedures to be conducted under local anesthesia may participate.
6. Participant has uncontrolled tumor-related pain:
Symptomatic lesions amenable to palliative radiotherapy (eg, bone metastases, or metastases causing nerve impingement) should be treated more than 7 days prior to the treatment initiation at C1D1.
Disease Characteristics
7. Participant has received radiotherapy for palliative purposes less than 7 days prior to treatment initiation at C1D1.
8. Participant has symptomatic brain metastases. A participant with asymptomatic or previously treated and stable brain metastases may participate in this study. Participants who have received definitive radiation or surgical treatment for symptomatic or unstable brain metastases and have been clinically stable and asymptomatic for at least 2 weeks
before Screening are eligible, provided they have been either off corticosteroid treatment or are receiving low-dose corticosteroid treatment (≤10 mg/day prednisone or equivalent) for at least 2 weeks prior to treatment allocation.
9. Participant has a history of leptomeningeal disease, or participant has spinal cord compression not definitively treated with surgery or radiation.
Prior/Concomitant Therapy or Clinical Study Experience
10. Taken any disallowed therapies as noted in Section 6.8, Concomitant Therapy before the planned first dose of study treatment.
11. Participant has received a live or live attenuated vaccine within 3 months before Cycle 1 Day 1. The seasonal influenza vaccine and non-live vaccines against COVID 19 are not
exclusionary.
12.2. For all cohorts with regimens potentially including lazertinib: Participant is currently receiving medications or herbal supplements known to be potent CYP3A4/5 inducers
and is unable to stop use for an appropriate washout period prior to Cycle 1 Day 1.
Other Exclusions
13. Any condition for which, in the opinion of the investigator, participation would not be in the best interest of the participant (eg, compromise well-being) or that could prevent,
limit, or confound the protocol-specified assessments.
14.1. Participant previously enrolled in the Sponsor’s studies 73841937NSC3003 (NCT04487080, MARIPOSA), 61186372NSC3001 (NCT04538664, PAPILLON) or 61186372NSC3002 (NCT04988295, MARIPOSA-2), or 61186372NSC3004 (NCT05388669, PALOMA-3).
Viral Hepatitis Assessments
15. Participant has at Screening any of the following:
    - Seropositive for hepatitis B: defined by a positive test for HBsAg. Participants with resolved infection (ie, participants who are HBsAg negative with antibodies to total anti-HBc with or without the presence of anti-HBs) must be screened using RT-PCR measurement of 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 (Appendix 10).
    - 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.
16. Other clinically active liver disease of infectious origin.
NOTE: Investigators must ensure that all study enrollment criteria have been met at screening. If a participant's clinical status changes (including any available laboratory results or receipt of additional medical records) after screening but before the first dose of study treatment is given such that the participant no longer meets all eligibility criteria, then the participant must be excluded from participation in the study. Section 5.5, Screen Failures, describes options for rescreening. The required source documentation to support meeting the enrollment criteria are noted in Appendix 3: Regulatory, Ethical, and Study Oversight Considerations.

Schema di trattamento: 

Cohort 4: 1.600 mg (o 2.240 mg se il peso corporeo è ≥80 kg); Amivantamab (SC-CF) sarà somministrato i Giorni 1 e 15 di ciascun ciclo di 28 giorni a partire dal Ciclo 1

Cohort 7: Amivantamab (SC-CF) sarà somministrato alla dose di 1600 mg (o 2240 mg se il peso corporeo del paziente è ≥80 kg) il Giorno 1 del Ciclo 1, e alla dose di 2400 mg (o 3360 mg se il peso corporeo del paziente è ≥80 kg) i Giorni 8 e 15 del Ciclo 1 e il Giorno 1 di ciascun ciclo successivo di 21 giorni.

Trattamento sperimentale: 

Amivantamab SC in monoterapia o con Lazertinib for cohort 4;
Amivantamab SC + carboplatin and pemetrexed for cohort 7

Trattamento di controllo: 

-

Obiettivi primari dello studio: 

Gli obiettivi primari sono valutare l’attività antitumorale (tasso di risposta obiettiva [objective response rate, ORR]) (tutte le Coorti ad eccezione della Coorte 4) e valutare la sicurezza (Coorte 4) di amivantamab SC-CF tramite iniezione manuale.

Obiettivi secondari dello studio: 

Gli obiettivi secondari sono valutare la sicurezza e le misure aggiuntive dell’attività antitumorale (tutte le Coorti ad eccezione della Coorte 4) e caratterizzare la PK di amivantamab-SC-CF (tutte le Coorti ad eccezione della Coorte 4). Solo nella Coorte 4, gli esiti riferiti dal paziente (patient-reported outcomes, PRO) saranno utilizzati per caratterizzare l’esperienza dei partecipanti con entrambe le formulazioni.

Note generali: 

NB: Arruolamento aperto per coorte 4, 7

Centri partecipanti

Nord Italia

Sud Italia e isole

Informazioni Generali

Protocollo

Numero di iscrizione a registro: 2022-000526-21

Data di inserimento: 05.07.2023

Data di aggiornamento: 30.09.2024

Promotore

Janssen Research & Development, LLC

Principal Investigator ITALIA

Riferimento: Dr. Info non disponibile

Telefono: 00000

Email: nd@nd.it

Localita: nd