Study of MK-4830 as Monotherapy and in Combination With Pembrolizumab (MK-3475) in Participants With Advanced Solid Tumors (MK-4830-001)

Inclusion Criteria:

Dose escalation participants: Has any histologically- or cytologically-confirmed advanced/metastatic solid tumor by pathology report and has received, has been intolerant to, or has been ineligible for all treatment known to confer clinical benefit. Solid tumors of any type are eligible for enrollment
Has measurable disease by Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST 1.1), Response Assessment in Neuro-Oncology (RANO), or modified RECIST (mRECIST) as assessed by the local site investigator/radiology
Submits an evaluable baseline tumor sample for analysis (either a recent or archival tumor sample). This inclusion criterion does not apply to Expansion phase Arm M
Dose Escalation Part C and Back-fill participants: Has 1 or more discrete malignant lesions that are amenable to biopsy
Has a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale. This inclusion criterion does not apply to Expansion phase Arm B
Demonstrates adequate organ function
A male participant must agree to use an approved contraception(s) during the treatment period and for at least 180 days after the last dose of study treatment and refrain from donating sperm during this period
A female participant is eligible to participate if she is not pregnant, not breastfeeding, and either not a woman of childbearing potential (WOCBP) OR if a WOCBP agrees to follow the study contraceptive guidance during the treatment period and for at least 180 days after the last dose of study treatment

Expansion phase Arm A participants:

Has histologically or cytologically confirmed metastatic pancreatic adenocarcinoma
Received at least 1 prior line of therapy and no more than 3 prior lines of systemic therapy

Expansion phase Arm B participants:

Has histologically or cytologically confirmed unresectable glioblastoma multiforme (GBM) or its variants
Has a Karnofsky performance status (KPS) ≥ 70
Has had no more than 1 prior line of therapy for GBM. Radiation with or without chemotherapy is acceptable as the prior treatment
Has shown unequivocal evidence for tumor progression by magnetic resonance imaging (MRI) or computed tomography (CT) scan by contrast within 2 weeks prior to randomization
Has an interval of at least 3 weeks (to randomization) between prior surgical resection (one week for stereotactic biopsy)
Has an interval of at least 12 weeks from the completion of radiation therapy to randomization unless there is unequivocal histologic confirmation of tumor progression or radiographic progression outside of the prior radiation field
Is neurologically stable (eg, without a progression of neurologic symptoms or requiring escalating doses of systemic steroid therapy within last 2 weeks) and clinically stable

Expansion phase Arm C participants:

Has histologically confirmed recurrent or metastatic head and neck squamous cell cancer (HNSCC) of the oral cavity, oropharynx, hypopharynx, and/or larynx that is considered incurable by local therapies
Has experienced disease progression at any time during or after treatment with a platinum-containing (eg, carboplatin or cisplatin) regimen with or without cetuximab

Expansion phase Arm D participants:

Has histologically confirmed advanced or metastatic HNSCC of the oral cavity, oropharynx, hypopharynx, and/or larynx that is considered incurable by local therapies
Has not had any prior programmed cell death 1 (PD-1)/ programmed cell death ligand 1 (PD-L1) therapy

Expansion phase Arms E and F participants:

Has a histologically or cytologically confirmed diagnosis of advanced (Stage IIIb) or Stage IV metastatic non-small-cell lung cancer (NSCLC)
Has received no prior systemic therapy for chemotherapy or other targeted or biological antineoplastic therapy treatment for Stage IIIb or Stage IV metastatic NSCLC. Treatment with chemotherapy and/or radiation as part of neoadjuvant/adjuvant therapy is allowed if therapy was completed at least 6 months prior to the diagnosis of advanced disease. Participants with prior treatment with an anti-PD-1 or PD-L1 agent are not eligible

Expansion phase Arm G participants:

Has a histologically or cytologically confirmed diagnosis of advanced (Stage IIIb) or Stage IV metastatic nonsquamous NSCLC (American Joint Committee on Cancer (AJCC) version 8)
Is able to tolerate chemotherapy with carboplatin and pemetrexed
Has received no prior systemic therapy for advanced NSCLC

Expansion phase Arm H participants:

Has histologically confirmed diagnosis of renal cell cancer (RCC) with clear cell component with or without sarcomatoid features
Has locally advanced/metastatic disease or has recurrent disease
Has received no prior systemic therapy for advanced RCC

Expansion phase Arm I participants:

Has histologically confirmed diagnosis of recurrent and/or metastatic gastric or gastroesophageal junction adenocarcinoma that is considered incurable by local therapies
Has received and progressed on at least two prior chemotherapy regimens
If tumor was if human epidermal growth factor receptor 2 (HER2/neu) positive, participant must have previously received treatment with trastuzumab

Expansion phase Arm J participants

Has histologically confirmed high-grade epithelial ovarian, fallopian tube or primary peritoneal carcinoma
Has received prior systemic therapy
Has radiographic evidence of disease progression
Is a candidate for paclitaxel chemotherapy

Expansion phase Arm K participants:

Has locally recurrent inoperable breast cancer OR have metastatic breast cancer not previously treated
Has confirmed triple-negative breast cancer (TNBC)
Has completed treatment for Stage I-III breast cancer, if indicated, and ≥6 months elapsed between the completion of treatment and first documented local or distant disease recurrence
Has been treated with (neo)adjuvant anthracycline

Expansion phase Arm L participants:

Has histologically confirmed diagnosis of recurrent and/or advanced mesothelioma that is considered incurable by standard therapies
Is eligible to receive standard chemotherapy

Expansion phase Arm M participants

Has any histologically or cytologically confirmed advanced/metastatic solid tumor by pathology report and have received, been intolerant of, been ineligible for, or refused all treatment known to confer clinical benefit
Has received up to 2 prior systemic regimens for the treatment of advanced/metastatic solid tumor
Is a Chinese participant residing in China

Coformulation Arm N participants

Has any histologically- or cytologically-confirmed advanced/metastatic solid tumor by pathology report and have received, been intolerant to, been ineligible for, or refused all treatment known to confer clinical benefit

Exclusion Criteria:

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 from any adverse events (AEs) that were due to cancer therapeutics administered more than 4 weeks earlier
Has not recovered from all radiation-related toxicities to Grade 1 or less, requires corticosteroids, and had radiation pneumonitis
Has a history of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 2 years
Has known untreated central nervous system metastases or known carcinomatous meningitis. This exclusion criterion does not apply to Expansion phase Arm B
Has received any prior immunotherapy and was discontinued from that treatment due to a Grade 3 or higher immune-related AEs
Has previously had a severe hypersensitivity reaction to treatment with a monoclonal antibody or has a known sensitivity to any component of pembrolizumab and/or chemotherapy agents
Has an active infection requiring therapy
Has a history or current interstitial lung disease
Has a history of noninfectious pneumonitis that required steroids or current pneumonitis
Has an active autoimmune disease that has required systemic treatment in the past 2 years except vitiligo or resolved childhood asthma/atopy
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
Has a known history of human immunodeficiency virus (HIV)
Has a known active hepatitis B or C
Is taking chronic systemic steroids in doses >10 mg daily of prednisone or equivalent within 7 days prior to the first dose of trial treatment
Has not fully recovered from any effects of major surgery without significant detectable infection. Surgical proceduress that required general anesthesia must be completed at least 2 weeks before first study treatment administration. Surgery requiring regional/epidural anesthesia must be completed at least 72 hours before first study treatment administration and participants should be recovered
Has received a live or live-attenuated virus vaccine within 30 days prior to first dose of study intervention
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-4830

All Expansion phase participants:

Tumor types with known MSI-high status are not eligible

Expansion phase Arm A participants:

Has received more than 3 lines of prior therapy for advanced disease (pancreatic cancer)

Expansion phase Arm B participants:

Has tumor primarily localized to the brainstem or spinal cord
Has presence of diffuse leptomeningeal disease or extracranial disease
Has recurrent tumor greater than 6 cm in maximum diameter
Requires treatment with moderate or high dose systemic corticosteroids for at least 3 days within 2 weeks of randomization

Expansion phase Arm D participants:

Has received prior systemic chemotherapy or other targeted or biological antineoplastic therapy treatment for their advanced metastatic HNSCC

Expansion phase Arm E and F participants:

Has received prior systemic chemotherapy or other targeted or biological antineoplastic therapy treatment for their Stage IIIb or Stage IV metastatic NSCLC
Has had prior treatment with any anti-PD-1, PD-L1, or programmed cell death-ligand 2 (PD-L2) agent

Expansion phase Arm G participants:

Has received prior systemic chemotherapy or other targeted or biological antineoplastic therapy treatment for their Stage IIIb or Stage IV nonsquamous NSCLC
Has had prior treatment with any anti-PD-1, PD-L1, or PD-L2 agent

Expansion phase Arm H participants:

Has received prior systemic anticancer therapy for advanced RCC with a tyrosine kinase inhibitor
Has a clinically significant gastrointestinal (GI) abnormality
Has a history of untreated deep vein thrombosis or pulmonary embolism within 6 months prior to screening
Has poorly controlled hypertension
Has active GI bleeding
Has evidence of inadequate wound healing
Has active bleeding disorder or other history of significant bleeding episodes within 30 days prior to randomization
Has hemoptysis within 6 weeks prior to randomization
Has radiographic evidence of encasement or invasion of a major blood vessel, or of intratumoral cavitation

Expansion phase Arm I participants:

Has experienced weight loss > 10 % over 2 months prior to first dose of study therapy
Has clinical evidence of ascites
Has peritoneal metastases

Expansion phase Arm J participants:

Has non-epithelial cancers, including borderline, malignant Müllerian mixed mucinous, malignant Brenner's tumor and undifferentiated carcinoma and/or germ cell tumors and/or sex cord - stromal tumors
Has received more than 2 prior lines of systemic therapy for ovarian cancer

Expansion phase Arm K participants:

Has a known history of hypersensitivity or allergy to the study chemotherapies and/or any of their components

Expansion phase Arm L participants:

Has a known history of hypersensitivity or allergy to the study chemotherapies and/or any of their components
Is receiving any medication prohibited in combination with study chemotherapies as described in the respective product labels, unless medication was stopped within 7 days prior to randomization

All Participants (Arms A through N)

Has symptomatic pleural effusion (eg, cough, dyspnea, pleuritic chest pain)
Has had an allogenic tissue/solid organ transplant.