PRIMARY OBJECTIVE:~I. Feasibility of achieving clinical benefit from SMMART Clinical Analytics Platform (SMMART-CAP) guided targeted interventions.~SECONDARY OBJECTIVES:~I. To assess the safety and tolerability of the assigned study intervention.~II. To determine overall (OS) and progression-free survival (PFS) for assigned study intervention.~EXPLORATORY OBJECTIVES:~I. To compare the time-to-progression (TTP) of a recommended targeted therapy regimen with the TTP for the most recent therapy on which the participant had progressed.~II. To determine the time to decline in a participant's ability to perform activities of daily living.~III. To measure quality of life among enrolled participants.~IV. To evaluate immune-mediated tumor response among participants receiving an immunomodulatory study drug (per Immune-related Response Evaluation Criteria in Solid Tumors [irRECIST]) as described in protocol.~V. To determine the rates of response to each SMMART-Adaptive Cancer Treatment (ACT) study intervention, as an individualized treatment strategy for participants with advanced solid tumors.~VI. Disease-specific survival of participants with advanced solid tumors. VII. To evaluate therapy induced changes in the tumor and tumor ecosystem. VIII. To identify mechanisms of therapy response and resistance.~OUTLINE:~PRE-SCREENING: Patients undergo a screening biopsy and blood collection for review and assessment of their tumor, utilizing one or more of the SMMART-CAP clinical assays. The clinical assays may be used to provide an optimal and individualized treatment approach which may or may not include a SMMART-ACT treatment regimen.~SMMART-ACT TREATMENT: Prior to enrollment, patients must receive a treatment recommendation that consists of one or more of the SMMART-ACT treatment regimens. Patients receive a targeted SMMART-ACT treatment regimen, based on the SMMART-CAP clinical assays, that may be administered alone or as part of a combination treatment regimen consisting of other targeted therapies, immunotherapies, chemotherapies, or radiation therapy or combinations thereof. For specific core study agents, a monotherapy lead-in may be considered for up to 4 weeks. After approximately 2 weeks of receiving the single agent, participants undergo an on-study tumor biopsy. At the completion of the monotherapy lead-in, participants proceed to receive the study agent in combination with other study agent(s) per their recommended study intervention. All other patients have the option to undergo a repeat biopsy during treatment. Treatment cycles repeat every 21 to 28 days in the absence of disease progression or unacceptable toxicity. Cycles are determined based on the study agent(s). Upon disease progression, patients are given the option to undergo an additional repeat biopsy.~Patients completing study treatment due to disease progression are followed every 3 months for 1 year, then every 6 months for 5 years. Patients completing study treatment without disease progression are followed every 6-12 weeks for up to 5 years or until disease progression, start of a new therapy, withdrawal from the study, or death, whichever occurs first.
This phase II trial determines if testing samples from a patients' cancer can be used to find specific drugs or drug combinations that can help control their disease. The safety and tolerability of the drug or drug combination is also to be studied. Another purpose is for researchers to study tumor cells to try to learn why some people respond to a certain therapy and others do not, and why some cancer drugs stop working.