Pembrolizumab plus lenvatinib as second-line plus intervention for select solid tumors

Phase 1

• Conditions: Triple negative breast cancer (TNBC), ovarian cancer, gastric cancer, colorectal cancer (CRC), glioblastoma (GBM), biliary tract cancers (BTC) or pancreatic cancer; MedDRA version: 21.1Level: PTClassification code 10028997Term: Neoplasm malignantSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2018-003747-37-IT
• Lead Sponsor: MERCK SHARP & DOHME CORP. UNA SUSSIDIARIA DI MERCK & CO. INC.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-06-15
• Last Update Posted: 30 August 2021

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 760

Inclusion Criteria

1. Have a histologically or cytologically-documented, advanced (metastatic and/or unresectable) solid tumor that is incurable and for which prior standard systemic therapy has failed in one of the following cohorts:
Cohort A Triple-Negative Breast Cancer (TNBC)
Cohort B Ovarian Cancer
Cohort C Gastric Cancer
Cohort D Colorectal Cancer
Cohort E Glioblastoma (GBM)
Cohort F Biliary Tract Cancer (BTC) (intrahepatic, extrahepatic cholangiocarcinoma and gall bladder cancer; excludes Ampulla of Vater)
Cohort G Pancreatic Cancer (ductal adenocarcinoma)
2. Participants must have fulfilled cohort-specific requirements regarding prior (line of therapy) treatments.
3. Participants must have progressed on or since the last treatment
4. Have measurable disease per RECIST 1.1 (RANO for the GBM cohort) as assessed by the local site investigator/radiology and confirmed by BICR. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions
5. Have provided a PD-L1 evaluable archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated. Formalin-fixed, paraffin embedded (FFPE) tissue blocks are preferred to slides. Newly obtained biopsies are preferred to archived tissue
6. Participants are at least 18 years of age; male or female for gastric cancer, GBM, TNBC, CRC, BTC, and pancreatic cancer cohorts; female only for ovarian cancer
7. Life expectancy of 12 weeks or more
8. Male participants are eligible to participate if they agree to the following during the intervention period and for at least 7 days after the last dose of lenvatinib:
a. Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent
OR
b. Must agree to use contraception unless confirmed to be azoospermic (vasectomized or secondary to medical cause) as detailed below:
- Agree to use a male condom plus partner use of an additional contraceptive method when having penile-vaginal intercourse with a WOCBP who is not currently pregnant
- 7 days after lenvatinib is stopped, if the participant is on pembrolizumab only, no male contraception measures are needed
9. A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least 1 of the following conditions applies:
- Is not a woman of childbearing potential (WOCBP)
OR
- Is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of <1% per year), with low user dependency, or be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis), during the intervention period and for at least 120 days post pembrolizumab or 30
days post lenvatinib, whichever occurs last.
The investigator should evaluate the potential for contraceptive method failure (ie, noncompliance, recently initiated) in relationship to the first dose of study intervention
- A WOCBP must have a negative highly sensitive pregnancy test (urine or serum as required by local regulations) within 24 hours before the first dose of study intervention
- If a urine test cannot be confirmed as negative (eg, an ambiguous result), a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive
10. The participant (or legally acceptable representative if applicable) has

Exclusion Criteria

1. Has presence of gastrointestinal condition including malabsorption that might affect the absorption of lenvatinib.
2. Has present or progressive accumulation of pleural, ascitic, or pericardial fluid requiring drainage or diuretic drugs within 2 weeks prior to enrollment. The participant can receive diuretic drugs as needed per the treating physician, outside of the above mentioned conditions. This exclusion applies to all cohorts except the ovarian cancer cohort.
3. Has radiographic evidence of major blood vessel invasion/infiltration.
4. Has clinically significant hemoptysis or tumor bleeding within 2 weeks prior to the first dose of study drug.
5. Has significant cardiovascular impairment within 12 months of the first dose of study drug.
6. Has a history of arterial thromboembolism within 12 months of start of study drug.
7. Has a known additional malignancy that is progressing or has required active treatment within the past 3 years.
8. Serious nonhealing wound, ulcer or bone fracture.
9. Has had major surgery within 3 weeks prior to first dose of study interventions.
10. Has biologic response modifiers (eg, granulocyte colony-stimulating factor) within 4 weeks before study entry. Chronic erythropoietin therapy is permitted provided that no dose adjustments were made within 2 months before first dose of study treatment.
11. Has pre-existing >=Grade 3 gastrointestinal (GI) or nongastrointestinal fistula.
12. Has received prior therapy with lenvatinib, 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, CD137).
13. Has received prior systemic anticancer therapy including investigational agents within 4 weeks prior to study treatment start.
14. Has recovered adequately from the toxicity and/or complications from the intervention if participant received major surgery prior to starting study treatment.
15. Has received prior radiotherapy within 2 weeks of start of study treatment.
16. Has received a live vaccine within 30 days prior to the first dose of study drug.
17. Has known intolerance to lenvatinib (and/or any of the excipients).
18. Has participated or is currently participating in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study intervention.
19. Has urine protein >=1 g/24h. Participants with proteinuria >1+ on urine dipstick testing will undergo 24-hour urine collection for quantitative assessment of proteinuria.
20. Has prolongation of QTc interval (calculated using Fridericia's formula) to >480 ms.
21. Has left ventricular ejection fraction (LVEF) <55% as determined by multigated acquisition scan (MUGA) or echocardiogram (ECHO).
22. 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 the first dose of study drug.
23. Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
24. Has tumors involving the brain stem.
25. Has severe hypersensitivity (>=Grade 3) to pembrolizumab and/or any of its excipients.
26. 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).
27. Has a history of (non-infectious) pneumonitis that required steroids or has current pneum

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified