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)

This study will investigate the safety, tolerability, pharmacokinetic (PK), and pharmacodynamic (PD) activity of adavosertib, both as monotherapy and in combination with gemcitabine, cisplatin, or carboplatin in participants with advanced solid tumors. Dose limiting toxicities (DLT) of adavosertib in combination with gemcitabine, cisplatin, or carboplatin will also be assessed. The primary hypotheses of the study are as follows: 1) Oral administration of adavosertib both as monotherapy and in combination with either gemcitabine, cisplatin, or carboplatin in patients with advanced solid tumors will be safe and tolerable, 2) The side effects observed in participants with advanced solid tumors after administration of adavosertib combined with each of the chemotherapies (gemcitabine, cisplatin and carboplatin) will allow for the definition of a single dose combination Maximum Administered Dose (MAD)/Maximum Tolerated Dose (MTD) and a multiple dose combination Biologically Effective Dose (BED)/MTD for each of the 3 combinations, 3) At a tolerated dose, adavosertib plasma exposure will exceed target thresholds established in preclinical models, and 4) At a tolerated dose, PD markers of adavosertib activity in combination with either gemcitabine, cisplatin, or carboplatin (in surrogate tissue and/or tumor) will meet or exceed the target threshold established in preclinical models.

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.

Eligibility Criteria:
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