(12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date WO 2016/141169 Al 9 September 2016 (09.09.2016) P O P C T (51) International Patent Classification: (74) Agent: AKHAVAN, Ramin; Caris MPI, Inc., 6655 N. A61K 31/335 (2006.01) G01N 33/50 (2006.01) MacArthur Blvd., Irving, TX 75039 (US). A61K 39/395 (2006.01) G01N 33/53 (2006.01) (81) Designated States (unless otherwise indicated, for every C12Q 1/68 (2006.01) G01N 33/00 (2006.01) kind of national protection available): AE, AG, AL, AM, C40B 30/04 (2006.01) AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, (21) International Application Number: BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, PCT/US2016/020657 DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IR, IS, JP, KE, KG, KN, KP, KR, (22) International Filing Date: KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, MG, 3 March 2016 (03.03.2016) MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, (25) Filing Language: English PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, (26) Publication Language: English TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. (30) Priority Data: (84) Designated States (unless otherwise indicated, for every 62/127,769 3 March 2015 (03.03.2015) kind of regional protection available): ARIPO (BW, GH, 62/167,659 28 May 2015 (28.05.2015) GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, (71) Applicant: CARIS MPI, INC. [US/US]; 6655 N. MacAr- TZ, UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, thur Blvd., Irving, TX 75039 (US). TJ, TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, (72) Inventors: SPETZLER, David; 6045 N. 40th St., Para LV, MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, dise Valley, AZ 85253 (US). ABBOTT, Brian; 3300 SM, TR), OAPI (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, Jasper Road, Great Falls, MT 59404 (US). ELLIS, Philip; GW, KM, ML, MR, NE, SN, TD, TG). 8538 W John Cabot Rd, Peoria, AZ 85382 (US). REDDY, Sandeep; 3712 Kempton Drive, Los Alamitos, CA 90720 Published: (US). — with international search report (Art. 21(3)) (54) Title: MOLECULAR PROFILING FOR CANCER 34 — 2 3 / DISPLAY . J INPUT PRINTER DEVICE EXTERNAL DATABASES y 5¾ DATABASES (57) Abstract: Provided herein are methods and systems of molecular profiling of diseases, such as cancer. In some embodiments, the molecular profiling can be used to identify treatments for the disease, such as treatments that provide likely benefit or likely lack o of benefit for the disease. The molecular profiling can include analysis of a sequence of a nucleic acid. The invention provides a method of identifying at least one treatment associated with a cancer in a subject. In still another related aspect, the invention provides use of a reagent in carrying out the methods of the invention, and/or use of a reagent in the manufacture of a reagent or kit o for carrying out the methods of the invention. In an aspect, the invention provides a system for identifying at least one treatment as - sociated with a cancer in a subject. MOLECULAR PROFILING FOR CANCER CROSS-REFERENCE This application claims the benefit of priority to United States Provisional Patent Application Serial Nos. 62/127,769, filed on March 3, 2015, and 62/167,659, filed on May 28, 2015; all of which applications are incorporated by reference herein in their entirety. BACKGROUND [0001] Disease states in patients are typically treated with treatment regimens or therapies that are selected based on clinical based criteria; that is, a treatment therapy or regimen is selected for a patient based on the determination that t e patient has been diagnosed with a particular disease (which diagnosis has been made from classical diagnostic assays). Although the molecular mechanisms behind various disease states have been the subject of studies for years, the specific application of a diseased individual's molecular profile in determining treatment regimens and therapies for that individual has been disease specific and not widely pursued. [0002] Some treatment regimens have been determined using molecular profiling in combination with clinical characterization of a patient such as observations made by a physician (such as a code from the International Classification of Diseases, for example, and the dates such codes were determined), laboratory test results, x-rays, biopsy results, statements made by the patient, and any other medical information typically relied upon by a physician to make a diagnosis in a specific disease. However, using a combination of selection material based on molecular profiling and clinical characterizations (such as the diagnosis of a particular type of cancer) to determine a treatment regimen or therapy presents a risk that an effective treatment regimen may be overlooked for a particular individual since some treatment regimens may work well for different disease states even though they are associated with treating a particular type of disease state. [0003] Patients with refractory or metastatic cancer are of particular concern for treating physicians. The majority of patients with metastatic or refractory cancer eventually run out of treatment options or may suffer a cancer type with no real treatment options. For example, some patients have very limited options after their tumor has progressed in spite of front line, second line and sometimes third line and beyond) therapies. For these patients, molecular profiling of their cancer may provide the only viable option for prolonging life. [0004] More particularly, additional targets or specific therapeutic agents can be identified assessment of a comprehensive number of targets or molecular findings examining molecular mechanisms, genes, gene expressed proteins, and/or combinations of such in a patient's tumor. Identifying multiple agents that can treat multiple targets or underlying mechanisms would provide cancer patients with a viable therapeutic alternative on a personalized basis so as to avoid standar therapies, which may simply not work or identify therapies that would not otherwise be considered by the treating physician. [0005] There remains a need for better theranostic assessment of cancer vicitims, including molecular profiling analysis that identifies at least one individual profile to provide more informed and effective personalized treatment options, resulting in improved patient care and enhanced treatment outcomes. The present invention provides methods and systems for identifying treatments for these individuals by molecular profiling a sample from the individual. The molecular profiling can include analysis of immune modulators such as PD-1 and/or its ligand PD-L1. SUMMARY OF THE INVENTION [0006] The present invention provides methods and system for molecular profiling, using t e results from molecular profiling to identify treatments for individuals. In some embodiments, the treatments were not identified initially as a treatment for the disease or disease lineage. The molecular profiling can include analysis of a sequence of a nucleic acid. The sequence can be assessed in multiple aspects, e.g., for t e presence or absence of any detectable chromosomal or transcript abnormality. Such a chromosomal or transcript abnormality may comprise without limitation a mutation, a polymorphism, a deletion, an insertion, a substitution, a translocation, a fusion, a break, a duplication, an amplification, a repeat, a copy number variant, a DNA methylation variation, a transcript expression level, a transcript variant, and a splice variant. [0007] In an aspect, the invention provides a method of identifying at least one treatment associated with a cancer in a subject, comprising: a) determining a molecular profile for at least one sample from the subject by assessing a plurality of genes and/or gene products; and b) identifying, based on the molecular profile, at least one of: i) at least one treatment that is associated with benefit for treatment of the cancer; ii) at least one treatment that is associated with lack of benefit for treatment of the cancer; and iii) at least one treatment associated with a clinical trial. The plurality of genes and/or gene products can be chosen from amongst genes and or gene products (e.g., transcripts and proteins) with efficacy known to be related to various chemotherapeutic agents. In one non-limiting example, it may be known that an individual with a tumor that express a certain biomarker has likely benefit of a given treatment whereas an individual with a tumor that does not express that biomarker has likely lack of benefit of the treatment. For example, HER2+ tumors may respond to the anti-HER2 antibody whereas HER2- tumors would likely receive no benefit from such treatment. In another non-limiting example, a certain drug may have likely benefit from a tumor carrying a wild type gene but not effective against a tumor carrying a given mutation in the same gene. For example, tumors with EGFR wild type may be treatable with an EGFR tyrosine kinase inhibitor (TKI), such as gefitinib and erlotinib, whereas EGFR T790M mutants are resistant to such treatments. [0008] In an embodiment of the method of the invention, the cancer comprises a bladder cancer and assessing the plurality of genes and/or gene products comprises protein analysis of at least one, e.g., 1, 2, 3, 4, 5, 6, 7, 8 or 9, of ERCC1, Her2/Neu, PD-L1, PTEN, RRM1, TOP2A, TOPOl, TS, TUBB3; and/or nucleic acid analysis of at least TOP2A.