Phase 2 study of lenvatinib plus pembrolizumab for advanced melanoma in anti-PD-1/L1-exposed participants
- Conditions
- Advanced melanomaMedDRA version: 20.0 Level: LLT Classification code 10053571 Term: Melanoma System Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2018-002518-10-ES
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- Not specified
- Target Recruitment
- 100
1. Have histologically or cytologically confirmed melanoma
2. Have unresectable Stage III or Stage IV melanoma, per American Joint Committee on Cancer (AJCC) staging system version 8, not amenable to local therapy
3. Have the presence of at least 1 measurable lesion by CT or MRI per RECIST 1.1 as confirmed by BICR. Cutaneous lesions and other superficial lesions are not considered measurable lesions for the purposes of this protocol, but may be considered as non-target lesions
4. Patients must have progressed on treatment with an anti-PD-1/L1 mAb administered either as monotherapy, or in combination with other checkpoint inhibitors or other therapies. PD-1 treatment progression is defined by meeting all of the following criteria:
a. Received at least 2 doses of an approved anti-PD-1/L1 mAb
b. Has demonstrated disease progression after PD-1/L1 as defined by RECIST 1.1. The initial evidence of disease progression is to be confirmed by a second assessment no less than 4 weeks from the date of the first documented progressive disease, in the absence of rapid clinical progression
c. Progressive disease has been documented within 12 weeks from the last dose of anti-PD-1/L1 mAb
5. Have submitted pre-trial imaging
6. Have an ECOG performance status 0 to 1
7. Have provided a baseline tumor biopsy
8. Have resolution of toxic effect(s) of the most recent prior therapy to Grade 1 or less (except alopecia). If participant received major surgery or radiation therapy of >30 Gy, they must have recovered from the toxicity and/or complications from the intervention
9. Be Male or Female and is at least 18 years of age at the time of signing the informed consent
10. A male participant must agree to use a contraception during the treatment period and for at least 120 days after the last dose of study intervention and refrain from donating sperm during this period
11. A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least 1 of the following conditions applies:
a. Not a woman of childbearing potential (WOCBP)
OR
b. A WOCBP who agrees to follow the contraceptive guidance during the treatment period and for at least 120 days after the last dose of study intervention
12. Have provided written informed consent for the study
13. Have adequately controlled BP, with or without antihypertensive medications, defined as BP =150/90 mm Hg at Screening and no change in antihypertensive medications within 1 week before Cycle 1 Day 1
14. Have adequate organ function
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 60
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 40
1. 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 before the first dose of study treatment
2. Has a known additional malignancy that is progressing or requires active treatment. Exceptions include early stage cancers (carcinoma in situ or Stage 1, non-ulcerated primary melanoma <1 mm in depth with no nodal involvement) treated with curative intent, basal cell carcinoma of the skin, squamous cell carcinoma of the skin, in situ cervical cancer, or in situ breast cancer that has undergone potentially curative therapy
3. Has known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated CNS metastases may participate provided they are stable (without evidence of progression by imaging for at least 4 weeks before the first dose of study treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases confirmed by repeat imaging, and have not required steroids for at least 14 days before study treatment
4. Has ocular melanoma
5. Has known hypersensitivity to active substances or any of their excipients including previous clinically significant hypersensitivity reaction to treatment with another monoclonal antibody
6. Has an active autoimmune disease that has required systemic treatment in past 2 years (ie, 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
7. Has an active infection requiring systemic therapy
8. Has known history of HIV (HIV 1/2 antibodies). No testing of HIV is required unless mandated by local health authority
9. Has known history of or is positive for hepatitis B (hepatitis B surface antigen [HBsAg] reactive) or hepatitis C (HCV RNA [qualitative] is detected). No testing of hepatitis B or C is required unless mandated by local health authority
10. Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis
11. Has a history of active tuberculosis (Bacillus tuberculosis)
12. Has presence of a gastrointestinal condition including malabsorption, gastrointestinal anastomosis, or any other condition that might affect the absorption of lenvatinib
13. Has a pre-existing Grade =3 gastrointestinal or non-gastrointestinal fistula
14. Has radiographic evidence of major blood vessel invasion/infiltration. The degree of tumor invasion/infiltration of major blood vessels should be considered because of the potential risk of severe hemorrhage associated with tumor shrinkage/necrosis following lenvatinib therapy
15. Has clinically significant hemoptysis or tumor bleeding within 2 weeks prior to the first dose of study drug
16. Has clinically significant cardiovascular disease within 12 months from first dose of study drug, including New York Heart Association Class III or IV congestive heart failure, unstable angina, myocardial infarction, cerebral vascular accident, or cardiac arrhythmia associa
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method