A Dose Escalation Study of Adavosertib (MK-1775) in Combination With Either Gemcitabine, Cisplatin, or Carboplatin in Adults With Advanced Solid Tumors (MK-1775-001)

Part 1 consists of single dose adavosertib monotherapy. If well tolerated, participants in Part 1 will continue on to one of three treatment arms in Part 2-A which consists of a single lower dose of adavosertib in combination with standard chemotherapy: 1) Adavosertib +Gemcitabine (1000 mg/m^2), 2) Adavosertib + Cisplatin (75 mg/m^2) or 3) Adavosertib +Carboplatin at an area under the time curve concentration of 5 mg/min/ml (AUC5). Following completion of Part 2-A, adavosertib will be administered twice daily (BID) for 2.5 days (multi-dose) starting concomitantly with each administration of chemotherapy in Part 2-B. After a preliminary combination MTD of adavosertib and chemotherapy has been established in Part 2B, the MTD confirmation expansion will occur in Part 3.

Inclusion criteria

• Must have a histologically confirmed metastatic or locally advanced solid tumor, progressed despite standard therapy, or for which standard therapy does not exist
• Must have performance status of <=1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale
• Female participants must not be pregnant

Exclusion criteria

• Has had chemotherapy, radiotherapy, or biological therapy within 4 weeks prior to entering the study or who has not recovered from adverse events due to agents given more than 4 weeks earlier
• Is participating or has participated in a study with an investigational compound or device within 30 days
• Has active central nervous system (CNS) metastases and/or carcinomatous meningitis. However, participants with CNS metastases who have completed a course of therapy would be eligible for the study provided they are clinically stable for 1 month prior to entry
• Has a primary central nervous system tumor
• Is allergic to any of the components of the combination study therapy or its analogs
• Participant has had prescription or non-prescription drugs or other products known to be metabolized by Cytochrome P450 3A4 (CYP3A4) that cannot be discontinued prior to Day 1 of dosing and withheld throughout the study until 2 weeks after the last dose of study medication. Medications of particular concern are inhibitors of CYP3A4 (azole antifungals [ketoconazole, itraconazole], macrolide antibiotics [erythromycin, clarithromycin], cimetidine, aprepitant, Human Immunodeficiency Virus (HIV) protease inhibitors, nefrazodone, and the following inducers of CYP3A4: phenytoin, barbiturates and rifampicin, and substrates of CYP3A4 including statins (lovastatin, simvastatin), midazolam, terfenadine, astemizole, and cisapride
• Is a regular user (including "recreational use") of any illicit drugs or had a recent history (within the last year) of drug or alcohol abuse
• Pregnant or breastfeeding, or expecting to get pregnant during the time the study will be ongoing
• HIV-positive
• History of Hepatitis B or C
• Has symptomatic ascites or pleural effusion. A participant who is clinically stable following treatment for these conditions is eligible
• Participant must not have prior radiation therapy to more than 30% of the bone marrow and must have recovered for at least 3 weeks from the hematologic toxicity of prior radiotherapy
• Has had a prior stem cell or bone marrow transplant
• Has received more than 4 prior cytotoxic chemotherapy regimens
• Has a history suggestive of Li-Fraumeni Syndrome