Informations générales (source: ClinicalTrials.gov)
A Phase II, Monocentric, Single Arm Trial Evaluating the Efficacy and Safety of Pembrolizumab in Combination With Lenvatinib in Metastatic Uveal MElanoma Patients (PLUME)
Interventional
Phase 2
Institut Curie (Voir sur ClinicalTrials)
juillet 2022
septembre 2028
09 juillet 2024
Because we suspect that the benefit of anti-PD-1 in metastatic UM patients could vary
according to previous exposure to Tebentafusp (better efficacy of anti-PD-1 after
Tebentafusp), the combination of pembrolizumab and lenvatinib will be assessed in two
independent cohorts: cohort 1 with Tebentafusp-naive patients, and cohort 2 with patients
previously treated by Tebentafusp.
The study is a monocentric, phase II trial with a single-arm of treatment in each cohort.
Liver MRI and chest-abdomen-pelvis CT will be performed every 9 weeks until progressive
disease (PD), followed by a Follow-up visit within 28 days after last treatment intake.
Survival status will be registered after patient discontinuation.
Etablissements
| Les établissements d'Île-de-France ayant mis à jour leurs données Origine et niveau de fiabilité des données | |||||
|---|---|---|---|---|---|
| CLCC INSTITUT CURIE | 04/09/2024 13:49:42 | Contacter | |||
Critères
Tous
Inclusion Criteria:
1. Male/female participants who are at least 18 years of age on the day of signing
informed consent with histologically confirmed diagnosis of metastatic uveal
melanoma (UM).
2. (i) Not having been treated with Tebentafusp for cohort 1 (Tebentafusp-naive
patients) OR (ii) Having been previously treated with Tebentafusp for cohort 2.
3. Life expectancy > 3 months.
4. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
Evaluation of ECOG has to be performed at inclusion.
5. Male participants must agree to use contraception
6. A female participant is eligible to participate if she is not pregnant, not
breastfeeding, and at least one of the following conditions applies:
1. Not a woman of childbearing potential (WOCBP) OR
2. A WOCBP who agrees to follow the contraceptive guidance
7. Measurable disease based on RECIST 1.1. lesions situated in a previously irradiated
area are considered measurable if progression has been demonstrated in such lesions.
8. The participant (or legally acceptable representative if applicable) provides
written informed consent for the trial.
9. Have provided a newly obtained (or archival if no systemic treatment since the
sampling) core or excisional biopsy of a tumor lesion not previously irradiated.
10. Patients with French Social Security in compliance with the French law relating to
biomedical research
11. All other relevant medical conditions must be well-managed and stable, in the
opinion of the investigator, for at least 28 days prior to first administration of
study drug.
12. Have adequate organ function as defined in the protocol.
1. Male/female participants who are at least 18 years of age on the day of signing
informed consent with histologically confirmed diagnosis of metastatic uveal
melanoma (UM).
2. (i) Not having been treated with Tebentafusp for cohort 1 (Tebentafusp-naive
patients) OR (ii) Having been previously treated with Tebentafusp for cohort 2.
3. Life expectancy > 3 months.
4. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
Evaluation of ECOG has to be performed at inclusion.
5. Male participants must agree to use contraception
6. A female participant is eligible to participate if she is not pregnant, not
breastfeeding, and at least one of the following conditions applies:
1. Not a woman of childbearing potential (WOCBP) OR
2. A WOCBP who agrees to follow the contraceptive guidance
7. Measurable disease based on RECIST 1.1. lesions situated in a previously irradiated
area are considered measurable if progression has been demonstrated in such lesions.
8. The participant (or legally acceptable representative if applicable) provides
written informed consent for the trial.
9. Have provided a newly obtained (or archival if no systemic treatment since the
sampling) core or excisional biopsy of a tumor lesion not previously irradiated.
10. Patients with French Social Security in compliance with the French law relating to
biomedical research
11. All other relevant medical conditions must be well-managed and stable, in the
opinion of the investigator, for at least 28 days prior to first administration of
study drug.
12. Have adequate organ function as defined in the protocol.
1. A WOCBP who has a positive urine pregnancy test within 72 hours prior to allocation.
2. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or
with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg,
CTLA-4, OX 40, and CD137) for metastatic UM.
In contrast, prior therapy with Tebentafusp is permitted.
3. Has recently received prior systemic anti-cancer therapy including investigational
agents or biological agents [eg cytokines, antibodies or small molecules kinase
inhibitors within 3 weeks or nitrosoureas/mitomycin C within 6 weeks] prior to
allocation. Prior liver surgery or local treatment of metastases is allowed if there
is an unequivocal progression.
Note: Participants must have recovered from all AEs due to previous therapies to
≤Grade 1 or baseline. Participants with ≤Grade 2 neuropathy may be eligible.
Note: Do not administer for at least 2 weeks following major surgery and until
adequate wound healing.
4. Has received prior radiotherapy within 2 weeks of start of study intervention.
Participants must have recovered from all radiation-related toxicities, not require
corticosteroids, and not have had radiation pneumonitis. A 1-week washout is
permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease.
5. Has received a live vaccine within 30 days prior to the first dose of study drug.
Examples of live vaccines include, but are not limited to, the following: measles,
mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus
Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for
injection are generally killed virus vaccines and are allowed; however, intranasal
influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed.
Only mRNA vaccines are authorized to prevent SARS-CoV-2 infection (COVID-19) during
the trial.
6. Is currently participating in or has participated in a study of an investigational
agent or has used an investigational device within 4 weeks prior to the first dose
of study intervention.
7. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy
(in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of
immunosuppressive therapy within 7 days prior to the first dose of study drug.
8. Has a history of a second malignancy, unless potentially curative treatment has been
completed with no evidence of malignancy for 2 years.
Note: The time requirement does not apply to participants who underwent successful
definitive resection of basal cell carcinoma of the skin, squamous cell carcinoma of
the skin, superficial bladder cancer, in situ cervical cancer, or other in-situ
cancers
9. Has known active CNS metastases and/or carcinomatous meningitis. Brain imaging is
not required at inclusion if asymptomatic. Participants with previously treated
brain metastases may participate provided they are radiologically stable, i.e.
without evidence of progression for at least 4 weeks by repeat imaging (note that
the repeat imaging should be performed during study screening), clinically stable
and without requirement of steroid treatment for at least 14 days prior to first
dose of study intervention.
10. Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or lenvatinib and/or any
of their excipients.
11. Has active autoimmune disease that has required systemic treatment in the past 2
years (i.e. with use of disease modifying agents, corticosteroids or
immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or
physiologic corticosteroid replacement therapy for adrenal or pituitary
insufficiency, etc.) is not considered a form of systemic treatment and is allowed.
12. Has a history of (non-infectious) pneumonitis that required steroids or has current
pneumonitis.
13. Has an active infection requiring systemic therapy. Patients requiring systemic
antibiotics for infection must have completed therapy at least 1 week prior to the
first dose of study drug.
14. Has a known history of Human Immunodeficiency Virus (HIV) infection. HIV testing is
not required at allocation.
15. Has a known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg]
reactive) or known active Hepatitis C virus (defined as HCV RNA [qualitative] is
detected) infection. Note: no testing for Hepatitis B and Hepatitis C is required
unless mandated by local health authority.
16. Has a known history of active TB (Bacillus Tuberculosis).
17. Has a history or current evidence of any condition, therapy, or laboratory
abnormality that might confound the results of the study, interfere with the
subject's participation for the full duration of the study, or is not in the best
interest of the subject to participate, in the opinion of the treating investigator.
18. Has known psychiatric or substance abuse disorders that would interfere with
cooperation with the requirements of the trial.
19. Is pregnant or breastfeeding or expecting to conceive or father children within the
projected duration of the study, starting with the screening visit through 120 days
after the last dose of trial treatment.
20. Has had an allogenic tissue/solid organ transplant.
21. Concurrent or recent (less than 1 week prior inclusion) immunosuppressive
medications (including corticosteroids exceeding 10 mg daily of prednisone
equivalent, azathioprin); hydrocortisone at physiological doses is allowed;
22. Uncontrolled blood pressure (Systolic BP>150 mmHg and/or diastolic BP >90 mmHg) in
spite of an optimized regimen of antihypertensive medication.
23. Electrolyte abnormalities that have not been corrected as assessed by the
investigator.
24. Significant cardiovascular impairment: history of congestive heart failure from New
York Heart Association (NYHA) Class III or IV, unstable angina, myocardial
infarction or stroke within 12 months of the first dose of study drug, or cardiac
arrhythmia with hemodynamic instability. Note : medically controlled arrhythmia
would be permitted.
25. Bleeding or thrombotic disorders or subjects at risk for severe hemorrhage. The
degree of tumor invasion/infiltration of major blood vessels (e.g. carotid artery)
should be considered because of the potential risk of severe hemorrhage associated
with tumor shrinkage/necrosis following lenvatinib therapy.
26. Subjects having > 1+ proteinuria on urine dipstick testing unless a 24-hour urine
collection for quantitative assessment indicates that the urine protein is <1 g/24
hours.
27. Subjects who have not recovered adequately from any toxicity from other anti-cancer
treatment regimens and/or complications from major surgery prior to starting
therapy.
28. Has had major surgery within 3 weeks prior to first dose of study interventions.
Note: Adequate wound healing after major surgery must be assessed clinically,
independent of time elapsed for eligibility.
29. Has preexisting ≥Grade 3 gastrointestinal or non-gastrointestinal fistula
30. Has a LVEF below the institutional (or local laboratory) normal range, as determined
by multigated acquisition (MUGA) or echocardiogram (ECHO).
31. Prolongation of QTcF interval to >480 ms.
32. Gastrointestinal malabsorption or any other condition that might affect the
absorption of lenvatinib
33. Active hemoptysis (bright red blood of at least 0.5 teaspoon) within 3 weeks prior
to the first dose of study drug.