A Phase 3, Randomized Study to Evaluate the Efficacy and Safety of Pembrolizumab (MK-3475) plus Lenvatinib (E7080/MK-7902) plus Chemotherapy Compared with Standard of Care Therapy as First-line Intervention in Participants with Advanced/Metastatic HER2 Negative Gastric/Gastroesophageal Junction Adenocarcinoma (LEAP-015)
- Conditions
- Advanced/Metastatic HER2 Negative Gastric/Gastroesophageal Junction AdenocarcinomaMedDRA version: 21.1Level: LLTClassification code 10071114Term: Metastatic gastric adenocarcinomaSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2020-001990-53-IT
- Lead Sponsor
- MERCK SHARP & DOHME CORP. UNA SUSSIDIARIA DI MERCK & CO. INC.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 790
1.Has histologically and/or cytologically confirmed diagnosis of previously untreated, locally advanced unresectable or metastatic HER2 negative gastric or GEJ adenocarcinoma based on Siewert classification 1-3
2.Is not expected to require tumor resection during the treatment course
3.Is HER2-negative per CAP/ASCP/ASCO guidance, by local/central testing
4.Has measurable disease as defined by RECIST 1.1 by scan with IV contrast as determined by the local site investigator/radiology assessment. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions since the completion of radiation (by scans with contrast)
5.Is male or female at least 18 years of age inclusive, at the time of signing the informed consent
6.Male participants are eligible to participate if they agree to the following during the intervention period and for at least 7 days after last dose of lenvatinib or 90 days after last dose of chemotherapy, whichever comes last:
• Refrain from donating sperm
PLUS either:
• 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 as detailed below unless confirmed to be azoospermic (vasectomized or secondary to medical cause):
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, no male contraception measures are needed
7.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 through 120 days after last dose of pembrolizumab, 30 days after last dose of lenvatinib, or 180 days after last dose of chemotherapy whichever occurs last, or not to donate eggs (ova, oocytes) to others or freeze/store for her own use for the purpose of reproduction during this period.
• 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
8.The participant (or legally acceptable representative) has provided documented informed consent/assent for the study
9.Has a performance status of 0 or 1 on the ECOG Performance Scale within 3 days prior to the first dose of study treatment
10.Has provided a tumor tissue sample for PD-L1 and MSI biomarker analysis. In addition, the PD-L1 result must be determined as positive or negative, before randomization
11.Has adequately controlled BP with or without antihypertensive medications, defined as BP =150/90 mm Hg and no change in antihypertensive medications within 1 week prior to randomization
12.Has adequate organ function. Specimens must be collected within 10 days prior to the start of study intervention
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 450
F.1.3 E
1.Has had previous therapy for locally advanced unresectable or metastatic gastric/GEJ cancer
2.Has had major surgery within 28 days prior to first dose of study interventions
3.Has had radiotherapy within 14 days of randomization.
4.Has a known additional malignancy that is progressing or has required active treatment within the past 5 years
5.Has known CNS metastases and/or carcinomatous meningitis
6.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
7.Has had an allogeneic tissue/solid organ transplant
8.Has perforation risks or significant GI bleeding, such as:
-Has had a serious nonhealing wound, peptic ulcer, or bone fracture within 28 days prior to randomization
-Has preexisting >=Grade 3 GI or non-GI fistula
-Has significant bleeding disorders, vasculitis, or has had a significant bleeding episode from the GI tract within 12 weeks prior to randomization
9.Has GI obstruction, poor oral intake (CAPOX patients), or difficulty in taking oral medication (CAPOX patients)
10.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 coinhibitory TCR
11.Has received prior therapy with anti-VEGF TKI or anti-VEGF mAb
12.Has received a live or live-attenuated vaccine within 30 days before the first dose of study drug
13.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
14.Has an active autoimmune disease that has required systemic treatment in past 2 years. Replacement therapy is not considered a form of systemic treatment and is allowed
15.Has radiographic evidence of encasement or invasion of a major blood vessel, or of intratumoral cavitation
16.Has inadequate cardiac function assessed as:
-Left ventricular ejection fraction (LVEF) below the institutional normal range as determined by a MUGA or ECHO
-QTcF value >470 msec for males and >480 msec for females
17.Has proteinuria >1+ on urine dipstick/urine analysis, with UPC >=1
18.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 intervention
19.Has a history of (noninfectious) pneumonitis that required steroids or current pneumonitis
20.Has a known history of active TB (Mycobacterium tuberculosis)
21.Has an active infection requiring systemic therapy
22.Has poorly controlled diarrhea (eg, watery stool, uncontrollable bowel movement with supportive medication, Grade >=2 and number of defecations, >=5/day)
23.Has accumulation of pleural, ascitic, or pericardial fluid requiring drainage or diuretic drugs within 2 weeks prior to enrollment
For the remaining exclusion creteria refer to Protocol
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