This is a first-in-human, multicenter, multi-arm, open label, non-randomized, Phase 1 study of MK-1308 in combination with pembrolizumab in participants with a histologically or cytologically confirmed diagnosis of an advanced solid tumor.
treatment purpose
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
For Dose Confirmation Phase NSCLC Arms (A, B, C, and E):
- Have newly diagnosed histologically or cytologically-confirmed stage IIIB/stage IV NSCLC. Epidermal growth factor receptor (EGFR)-and anaplastic lymphoma kinase (ALK) translocation-directed therapy is not indicated as primary therapy. 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
For Dose Confirmation Phase SCLC Arm (Arm D):
- Have histologically- or cytologically-confirmed metastatic (Stage III/IV) SCLC with progressive disease after >=1 platinum-based chemotherapy regimen. Participants with platinum-sensitive disease are eligible
Have measurable disease by RECIST 1.1 as assessed by the local site investigator/radiology
- Have Eastern Cooperative Oncology Group (ECOG) Performance Scale status of 0 or 1
- 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 child bearing potential (WOCBP) OR
- Is a WOCBP and using a contraceptive method that is highly effective during the intervention period and for at least 120 days after the last dose of pembrolizumab or pembrolizumab/quavonlimab, whichever comes last
- Female participants of childbearing potential must have negative urine or serum pregnancy test within 24 hours for urine and within 72 hours for serum prior to receiving the first dose of study treatment
- Male participants with a female partner(s) of child-bearing 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 and refrain from donating sperm during this period
- Must submit an evaluable baseline tumor sample for analysis (either a recent or archival tumor sample)
- For all phases of the study: Has received previous treatment with another agent targeting cytotoxic T lymphocyte leukocyte antigen (CTLA)-4
For Dose Confirmation Phase:
- Has received previous treatment with another agent targeting programmed cell death protein 1 (PD-1), programmed cell death ligand 1 (PD-L1), or anti PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor
- 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 Common Toxicity Criteria for Adverse Events (CTCAE) Grade 1 or better from any AEs that were due to cancer therapeutics administered more than 4 weeks earlier
- Has received lung radiation therapy of >30 Gray (Gy) within 6 months before the first dose of study treatment
- 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 quavonlimab.
Has a history of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 3 years
For Dose Escalation Cohorts (1-3) and Dose Confirmation Arms (A-E):
- Has known untreated central nervous system (CNS) metastases. Has known carcinomatous meningitis
- Has received any prior immunotherapy and was discontinued from that treatment due to a Grade 3 or higher immune-related adverse events (irAE)
- Has had a severe hypersensitivity reaction to treatment with any monoclonal antibody or components of the study drug
- Has any active infection requiring therapy
- Has a history of interstitial lung disease, history of noninfectious pneumonitis that required steroids (or has current pneumonitis), or history of inflammatory bowel disease
- Has an active autoimmune disease that has required systemic treatment in the past 2 years
- Has clinically significant cardiac disease
- Has received a live or live attenuated vaccine within 28 days of planned treatment start
- Has known history of human immunodeficiency virus (HIV) and/or known active Hepatitis B or C infections, and/or known to be positive for hepatitis B surface antigen (HBsAg)/ hepatitis B virus (HBV) DNA
- Has known psychiatric or substance abuse disorders that would interfere with the participant's ability to cooperate with the requirements of the trial
- Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study, starting with screening and for up to 120 days following cessation of pembrolizumab or pembrolizumab/quavonlimab
- Has not fully recovered from any effects of major surgery without significant detectable infection
18age old over
No limit
Both
Advanced Solid Tumors
Biological: Quavonlimab
Quavonlimab is administered intravenously (IV) during the Dose Escalation Phase and Dose Confirmation Phase at either DL1 or DL2, and is administered IV during the Efficacy Expansion Phase at DL2.
Other Names:
MK-1308
Biological: Pembrolizumab
Pembrolizumab is administered IV at PDL1 on Day 1 of each cycle starting Cycle 2 for the Dose Escalation Phase or starting Cycle 1 of the Dose Confirmation Phase. Pembrolizumab is administered IV at PDL2 on Day 1 of each cycle for the Efficacy Expansion Phase (Arm G).
Other Names:
Keytruda(TM)
Number of participants with a Dose Limiting Toxicity (DLT), AE, Clinical Safety Laboratory Assessments, Vital Signs.
- Number of participants with >=1 DLT
- Number of participants with >=1 AE
- Number of participants discontinuing study treatment due to an AE
- To characterize the PK profiles and incidence of ADA, as appropriate, of pembrolizumab,of MK-1308 as monotherapy,and of MK-1308when used in combination and in coformulation with pembrolizumabin the dose escalation phase
- Anti-drug antibody levels
- To evaluate ORR as assessed by investigator per RECIST 1.1 in the dose escalation phase,the doseconfirmation phase
