A Phase 1 /2 Trial of MK-1308 in Subjects with Advanced Solid Tumors
- Conditions
- Advanced Solid Tumors - first-line, advanced/metastatic NSCLC and second-line (and beyond) advanced/metastatic SCLCMedDRA version: 21.1Level: PTClassification code 10059514Term: Small cell lung cancer metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 21.1Level: PTClassification code 10059515Term: Non-small cell lung cancer metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 21.1Level: PTClassification code 10025670Term: Malignant melanoma stage IIISystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 21.1Level: PTClassification code 10025671Term: Malignant melanoma stage IVSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2019-003703-35-PL
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 388
Male and female participants who are at least 18 years of age on the day of signing consent will be enrolled.
1) For Dose Escalation Phase: Have any histologically- or cytologically-confirmed advanced/metastatic solid tumor (except NSCLC for Cohorts 2 and 3) by pathology report and have received, been intolerant to, been ineligible for or refused all treatment known to confer clinical benefit.
2) For Dose Confirmation Phase, Arms A, B, C, E: Have newly diagnosed histologically or cytologically-confirmed stage IIIB/stage IV NSCLC:
The participant must not have received prior systemic treatment for advanced NSCLC or must have received previous neoadjuvant and adjuvant chemotherapies =6 months before dosing of study drug if prior systemic treatment was given for early stage disease. Diagnosis must be stated in a pathology report and pathologically confirmed at the study site by the investigator.
3) For Dose Confirmation Phase, Arm D: Have histologically- or cytologically confirmed metastatic (Stage III/IV) SCLC with progressive disease after at least one platinum-based chemotherapy regimen. Participants with platinum-sensitive (relapse =90 days after chemotherapy) or platinum-resistant (relapse <90 days after or during chemotherapy) disease are eligible. Diagnosis must be stated in a pathology report and pathologically confirmed at study site by the investigator.
4) Have measurable disease by RECIST 1.1 as assessed by the local site investigator/radiology. Target lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
5) Have a performance status of 0 or 1 on ECOG Performance Scale.
6) Demonstrate adequate organ function. All screening labs should be performed within the screening period.
7) 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 WOCBP
OR
Is a WOCBP and using a contraceptive method that is highly effective or be abstinent from heterosexual intercourse as their preferred and usual lifestyle during the intervention period and for at least 120 days after the last dose of pembrolizumab or MK-1308A, whichever comes last. A WOCBP must have a negative highly sensitive pregnancy test (urine or serum as required by local regulations) within 24 hours for urine and within 72 hours for serum before the first dose of study intervention.
8) Female participants of childbearing potential must be willing to use an adequate method of contraception, for the course of the study through 120 days after the last dose of study medication.
9) Male participants with a female partner(s) of child-bearing potential must agree to use an adequate method of contraception during the treatment period plus an additional 120 days after the last dose of study treatment and refrain from donating sperm during this period.
10) Has voluntarily agreed to participate by giving documented informed consent for the trial. The participant may also provide consent/assent for Future Biomedical Research. However, the participant may participate in the main trial without participating in Future Biomedical Research.
11) Must submit an evaluable baseline tumor sample for analysis (either a recent or archival tumor sample). Formalin-fixed, paraffin embedded (FFPE) tissue blocks are preferred to slides. If submitting unstained cut slides, freshly cut slides should be submitted to the testing laboratory within
1.For all phases of the study: Has received previous treatment with another agent targeting CTLA4
2.For Dose Confirmation Phase: Has received previous treatment with another agent targeting PD-1, PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, OX-40, CD137)
3.Has had chemotherapy, definitive radiation, or biological cancer therapy within 4 weeks (2 weeks for palliative radiation) prior to the first dose of study therapy, or has not recovered to CTCAE Grade 1 or better from any adverse events that were due to cancer therapeutics administered more than 4 weeks earlier (this includes participants with previous immunomodulatory therapy with residual immune related adverse events)
4.Has received lung radiation therapy of >30 Gy within 6 months before the first dose of study treatment
5.Is currently participating and receiving study therapy in a study of an investigational agent or has participated and received study therapy in a study of an investigational agent or has used an investigational device within 28 days of administration of MK-1308.
6.Has history of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 3years
7.For Cohorts 1-3 and Arms A through E ONLY: Has known untreated central nervous system (ie,brain and/or spinal cord) metastases. Has known carcinomatous meningitis.
8.Has received any prior immunotherapy and was discontinued from that treatment due to a Grade 3 or higher irAE
9.Previously had a severe hypersensitivity reaction to treatment with a monoclonal antibody or has a known sensitivity to any component of pembrolizumab
10. Has any active infection requiring therapy
11.Has a history of interstitial lung disease
12.Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis.
13.Has a history of inflammatory bowel disease
14.Has an active autoimmune disease that has required systemic treatment in the past 2 years (ie, with use of disease modifying agents, corticosteroids or immunosuppressive drugs) except vitiligo or resolved childhood asthma/atopy. Replacement therapy, such as thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, is not considered a form of systemic treatment and is allowed. Use of non-systemic steroids is permitted
15.Has clinically significant cardiac disease, including unstable angina, acute myocardial infarction within 6 months from Day 1 of study drug administration, or New York Heart Association Class III or IV congestive heart failure. Medically controlled arrhythmia stable on medication is permitted
16.Has received a live or live attenuated vaccine within 28 days of planned treatment start. Seasonal flu vaccines that do not contain live virus are permitted.
17.Participants with known history of HIV (HIV 1/2 antibodies) and/or active Hepatitis B or C, and/or positive HBsAg and HBVDNA. Active Hepatitis C is defined by a positive Hep C Ab result and quantitative HCV RNA results greater than the lower limits of detection of the assay
18.Has history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with participant’s participation for the full duration of the study, make administration of the study drugs hazardous or make it difficult to monitor adverse effects such that it is not in the best interest of the p
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