A Phase II Randomized Study Comparing the Efficacy and Safety of Targeted Therapy or Cancer Immunotherapy Versus Platinum-Based Chemotherapy in Patients With Cancer of Unknown Primary Site

Inclusion Criteria:

• Histologically-confirmed unresectable cancer of unknown primary site (CUP) diagnosedaccording to criteria defined in the 2015 European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for CUP

• No prior lines of systemic therapy for the treatment of CUP

• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

• Candidate for platinum-based chemotherapy (according to the reference informationfor the intended chemotherapy)

• At least one measurable lesion according to Response Evaluation Criteria in SolidTumors, version 1.1 (RECIST v1.1)

• Formalin-Fixed Paraffin-Embedded (FFPE) tumor tissue sample </= 4 months old that isexpected to be sufficient for generation of a comprehensive genomic profile at acentral reference pathology laboratory

Exclusion Criteria:

• Squamous cell CUP

• Participants who can be assigned to a specific subset of CUP for which a specifictreatment is recommended by the 2015 ESMO Clinical Practice Guidelines for CUP orwith a clinical and IHC profile indicative of a specific primary tumor (favorableprognosis CUP subsets): Poorly differentiated carcinoma with midline distribution;women with papillary adenocarcinoma of the peritoneal cavity; women withadenocarcinoma involving only the axillary lymph nodes; squamous cell carcinoma ofthe cervical lymph nodes; poorly differentiated neuroendocrine tumors; men withblastic bone metastases and elevated prostate-specific antigen (PSA); participantswith a single, small, potentially resectable tumor; colon cancer-type CUP, includingparticipants with a CK7 negative, CK20 positive, CDX-2 positive immunohistochemistryprofile; CK7-positive, CK20-negative and TTF-1 positive tumors in a contextsuggestive of lung adenocarcinoma or thyroid cancer; IHC profile definitelyindicative of breast cancer OR an IHC profile indicative of breast cancer and eithera history of breast cancer or lymph nodes in the drainage areas of the breast;high-grade serious carcinoma histology and elevated CA125 tumor marker and/or a massin the gynecological tract or any tumor mass or lymph node in the abdominal cavity;IHC profile suggestive of renal cell carcinoma and renal lesions, with a Bosniakclassification higher than IIF; IHC profile compatible with cholangiocarcinoma orpancreatobiliary (or upper gastrointestinal carcinoma) AND 1 or 2 liver lesionswithout extrahepatic disease or with only pulmonary metastases and/or lymph nodes inthe drainage areas of the liver

• Known presence of brain or spinal cord metastasis (including metastases that havebeen irradiated only)

• Histology and immunohistology profiles (per 2015 ESMO guidelines) that are notadenocarcinoma or poorly differentiated carcinoma/adenocarcinoma

• History or known presence of leptomeningeal disease

• Known human immunodeficiency virus (HIV) infection

• Significant cardiovascular disease

• Prior allogeneic stem cell or solid organ transplantation

• Pregnancy or breastfeeding, or intention of becoming pregnant during study treatmentor for up to 7 months after the final dose of treatment