A Phase 3, Randomized Study to Evaluate the Efficacy and Safety of Pembrolizumab (MK-3475) + Lenvatinib (E7080/MK-7902) + Chemotherapy Compared with Standard of Care as First-line Intervention in Participants with Metastatic Esophageal Carcinoma
- Conditions
- Metastatic squamous cell carcinoma of the esophagusMedDRA version: 21.0Level: LLTClassification code 10041824Term: Squamous cell carcinoma of esophagusSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2020-001911-26-ES
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 862
1. The participant must have a histologically or cytologically confirmed diagnosis of metastatic squamous cell carcinoma of the esophagus.
2. The participant must have measurable disease per RECIST 1.1 as determined by the local site investigator/radiology assessment. A lesion(s) situated in a previously irradiated area can be considered a target lesion(s) if progression has been demonstrated and the lesion(s) is considered measurable per RECIST 1.1 criteria.
3. Participants are at least 18 years of age on the day of signing the informed consent.
4. 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 or 90 days after the last dose of chemotherapy, whichever comes last:
• 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
• 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.
- Please note that 7 days after lenvatinib is stopped, if the participant is on pembrolizumab only and is greater than 90 days post chemotherapy, no male contraception measures are needed.
• Refrain from donating sperm during the chemotherapy treatment period and for at least 90 days after the last dose of chemotherapy.
5. A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies:
• Is not a 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 after the last dose of pembrolizumab, 30 days after the last dose of lenvatinib, or 180 days after the last dose of chemotherapy, whichever occurs last, and agrees not to donate eggs (ova, oocytes) to others or freeze/store for her own use for the purpose of reproduction during this period. 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 within 72 hours (serum) or 24 hours (urine) (as required by local regulations) before the starting 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.
• The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy.
6. The participant (or legally acceptable representative) provides documented informed consent/assent for the study.
7. Has an ECOG performance score of 0 to 1 assessed 0 to 3 days before randomization.
8. Has submitted a tumor tissue sample that meet the acceptance criteria for PD-L1 analysis before randomization. In addition, the PD-L1 composite score (CPS
1. Has had previous therapy for locally advanced unresectable or metastatic esophageal cancer. Participants may have received prior neoadjuvant or adjuvant therapy under specific circumstances.
2. Has locally advanced esophageal carcinoma.
3. Has metastatic adenocarcinoma of the esophagus.
4. Has direct invasion into adjacent organs such as the aorta or trachea (T4b disease).
5. Has radiographic evidence of > 90 degree encasement of a major blood vessel, or of intratumoral cavitation.
6. Has perforation risks or significant GI bleeding.
7. Has active hemoptysis (bright red blood of at least 0.5 teaspoon) within 3 weeks prior to the first dose of study drug or tumor bleeding within 2 weeks prior to the first dose of study intervention.
8. Has uncontrollable pleural effusion, pericardial effusion, or ascites requiring frequent drainage or medical intervention (clinically significant recurrence requiring an additional intervention within 2 weeks of randomization).
9. Has GI obstruction, poor oral intake, or difficulty in taking oral medication. Participants with existing esophageal stent are not eligible. Also, participants with known gastrointestinal malabsorption, gastrointestinal anastomosis or any other condition that may affect the absorption of lenvatinib.
10. Has had major surgery, open biopsy, or significant traumatic injury within 3 weeks prior to the first dose of study interventions, or anticipation of the need for major surgery during the course of study intervention.
11. 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, CD137) or has previously participated in a pembrolizumab clinical study.
12. Has received prior therapy with anti-VEGF TKI or anti-VEGF mAb.
13. Is currently receiving brivudine, sorivudine analogues, or other inhibitors of the enzyme dihydropyrimidine dehydrogenase.
14. Has received prior radiotherapy within 2 weeks of start of study intervention.
15. Has received a live or live attenuated vaccine within 30 days prior to the first dose of study intervention.
16. 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.
17. Has urine protein =1 g/24 hours.
18. Has inadequate cardiac function assessed as: QTcF value >470 msec for males and >480 msec for females (mean of 3 measurements corrected for HR using Fridericia's formula).
19. Has an LVEF below the institutional (or local laboratory) normal range, as determined by MUGA or ECHO.
20. 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 intervention, or has a history of organ transplant, including allogeneic stem cell transplant.
21. Has a known additional malignancy that is progressing or has required active treatment within the past 3 years.
22. Has known active CNS metastases and/or carcinomatous meningitis.
23. Has severe hypersensitivity (=Grade 3) to treatment with an mAb or known sensitivity or intolerance to any component of lenvatinib, pembrolizumab, study chemotherapy agents and/or to any excipients, murine proteins, or platinum containing products.
24. Has an active autoimmune disease that has required systemic
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