A Phase 1/2 Open-Label, Umbrella Platform Design Study of Investigational Agents With or Without Pembrolizumab (MK-3475) and/or Chemotherapy in Participants With Advanced Esophageal Cancer naïve to PD-1/PD-L1 Treatment
- Conditions
- Esophageal Squamous Cell Carcinoma (ESCC)MedDRA version: 25.1Level: LLTClassification code 10030186Term: Oesophageal squamous cell carcinoma NOSSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2021-005405-26-NO
- Lead Sponsor
- Merck Sharp & Dohme LLC
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 120
1.Histologically or cytologically confirmed diagnosis of metastatic or locally advanced unresectable ESCC
2.Have a life expectancy of greater than 3 months
3.Measurable disease per RECIST 1.1 as determined by the local site investigator/radiology assessment and verified by BICR. 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
4.Experienced investigator documented radiographic or clinical disease progression on one prior line of standard therapy. This study will only include 2L participants who have progressed during or after receiving at least one dose of standard therapy given in a 1L setting
5.Submits an evaluable baseline tumor sample for analysis. Newly obtained biopsies are preferred to archived tissue
6.Performance status of 0 or 1 on the ECOG Performance Scale before first dose of study intervention
7.Adequately controlled BP with or without antihypertensive medications, defined as BP =150/90 mm Hg with no change in antihypertensive medications within 1 week prior to allocation/randomization
8.Participants with a feeding tube to maintain adequate nourishment and for the administration of medications are allowed
9.Adequate organ function. Specimens must be collected within 7 days before the start of study intervention
10.At least 18 years of age on the day of providing documented informed consent
11.If male, agrees to the following during the intervention period and for at least the time needed to eliminate each study intervention after the last dose.The length of time required to continue contraception for each study intervention is as follows:
-Chemotherapy: 90 days
-Lenvatinib: 7 days
-Pembrolizumab, MK-4280A, and MK-4830: no contraception requirements
•Refrains from donating sperm
PLUS either:
•Abstains from heterosexual intercourse as their preferred and usual lifestyle and agrees to remain abstinent
OR
•Uses contraception unless confirmed to be azoospermic as detailed below:
-Uses a male condom plus partner use of an additional contraceptive method when having penile-vaginal intercourse with a WOCBP who is not currently pregnant
-Contraceptive use by men should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. If the contraception requirements in the local label for any of the study interventions is more stringent than the requirements above, the local label requirements are to be followed
12.A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies:
• Not a WOCBP
OR
• A WOCBP and:
-Uses 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 during the intervention period and for at least the time needed to eliminate each study intervention after the last dose of study intervention 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 length of time required to continue contraception for each study intervention is as follows:
-Chemotherapy: 180 days
-Lenvatinib: 30 days
-Pembrolizumab, MK-4280A, and MK-4830: 120 days
The investigator should evaluate the potential for contraceptive method failure in
1. Direct invasion into adjacent organs such as the aorta or trachea (T4b disease)
2. Experienced weight loss >10% over approximately 2 months prior to first dose of study therapy
3. Clinically apparent ascites or pleural effusion by physical examination
4. Received prior therapy with
-An anti–PD-1, anti–PD-L1, or anti–PD-L2 agent
-VEGF TKI (including lenvatinib) or anti-VEGF mAb
-Any agent directed to another stimulatory or coinhibitory T-cell receptor (eg, CTLA-4, OX-40, CD137)
-An anti-LAG-3 antibody
-An agent targeting ILT4 or HLA-G
5.Received prior systemic anticancer therapy within 2 weeks before allocation/randomization
6. Received prior radiotherapy within 2 weeks of start of study intervention or has radiation-related toxicities requiring corticosteroids.
7. Received a live or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines are allowed
8. Has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration
9. 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 medication
10. Known additional malignancy that is progressing or has required active treatment within the past 3 years
11. Known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, (ie, without evidence of progression) for at least 4 weeks as confirmed by repeat imaging performed during study screening, are clinically stable and have not required steroid treatment for at least 14 days before the first dose of study intervention
12. Severe hypersensitivity (Grade =3) to any study intervention and/or any of its excipients
13. 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) is not considered a form of systemic treatment and is allowed
14. History of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
15. Active infection requiring systemic therapy
16. History of HIV infection. HIV testing is not required unless mandated by local health authority
17. History of Hepatitis B (defined as HBsAg reactive) or known active Hepatitis C virus (defined as detectable HCV RNA [qualitative]) infection
18. History or current evidence of any condition, therapy, laboratory abnormality, or other circumstance that might confound the results of the study, interfere with the individual’s ability to cooperate with the requirements of the study, or interfere with the individual's participation for the full duration of the study, such that it is not in the best interest of the individual to participate, in the opinion of the treating investigator.
19. History of allogenic tissue/solid organ transplant
20. Had major surgery within 3 weeks prior to first dose of study interventions
21. Pre-existing active Grade =3 GI fistula
22. Urine protein =1 g/24 hours
23. A LVEF below the institutional (or local laboratory) normal range, as determined by MUGA or E
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