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WO 2018/223101 Al 06 December 2018 (06.12.2018) W !P O PCT

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WO 2018/223101 Al 06 December 2018 (06.12.2018) W !P O PCT (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 2018/223101 Al 06 December 2018 (06.12.2018) W !P O PCT (51) International Patent Classification: (71) Applicant: JUNO THERAPEUTICS, INC. [US/US]; 400 A 61K 35/1 7 (20 15.0 1) A 61P 35/00 (2006 .0 1) Dexter Ave. N., Suite 1200, Seattle, WA 98109 (US). (21) International Application Number: (72) Inventor: ALBERTSON, Tina; 400 Dexter Ave. N., Suite PCT/US2018/035755 1200, Seattle, WA 98109 (US). (22) International Filing Date: (74) Agent: AHN, Sejin et al; Morrison & Foerster LLP, 1253 1 0 1 June 2018 (01 .06.2018) High Bluff Drive, Suite 100, San Diego, CA 92130-2040 (US). (25) Filing Language: English (81) Designated States (unless otherwise indicated, for every (26) Publication Language: English kind of national protection available): AE, AG, AL, AM, (30) Priority Data: AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, BZ, 62/5 14,774 02 June 2017 (02.06.2017) US CA, CH, CL, CN, CO, CR, CU, CZ, DE, DJ, DK, DM, DO, 62/5 15,530 05 June 2017 (05.06.2017) US DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, 62/521,366 16 June 2017 (16.06.2017) u s HR, HU, ID, IL, IN, IR, IS, JO, JP, KE, KG, KH, KN, KP, 62/527,000 29 June 2017 (29.06.2017) u s KR, KW, KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, 62/549,938 24 August 2017 (24.08.2017) u s MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, 62/580,425 0 1 November 2017 (01 .11.2017) u s OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, 62/593,871 0 1 December 2017 (01 .12.2017) u s SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, 62/596,764 08 December 2017 (08.12.2017) u s TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. 62/614,957 08 January 2018 (08.01.2018) u s (54) Title: ARTICLES OF MANUFACTURE AND METHODS FOR TREATMENT USING ADOPTIVE CELL THERAPY FIG. 31A F I 1 mDOR (95% CI) 1 C "" " 4 » « — CR: NE {9.2 m -NE ¾ o > » All: NE (5.0 r o NE) 20 PR: 2.1 m ( 1. 1 mo- 3.9 mo) 0 2 5 8 11 1 7 2 3 At R s Time From First Response, months CR 56 48 37 21 5 7 1 PR 20 11 2 1 All 76 59 39 22 15 7 1 (57) Abstract: Provided are adoptive cell therapy methods involving the administration of doses of cells for treating disease and conditions, including certain B cell malignancies. The cells generally express recombinant receptors such as chimeric antigen receptors ∞ (CARs). In some embodiments, the methods are for treating subjects with non-Hodgkin lymphoma (NHL). In some embodiments, the methods are for treating subjects with relapsed or refractory NHL. Also provided are articles of manufacture and prophylactic treatments o in connection with adoptive therapy methods. o [Continued on nextpage] WO 2018/223101 Al llll II II 11III II I I II III (84) Designated States (unless otherwise indicated, for every kind of regional protection available): ARIPO (BW, GH, GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, TZ, UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, 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, LV, MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, SM, TR), OAPI (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, GW, KM, ML, MR, NE, SN, TD, TG). Declarations under Rule 4.17: — as to the applicant's entitlement to claim the priority of the earlier application (Rule 4.17(in)) Published: — with international search report (Art. 21(3)) — before the expiration of the time limit for amending the claims and to be republished in the event of receipt of amendments (Rule 48.2(h)) — with sequence listing part of description (Rule 5.2(a)) ARTICLES OF MANUFACTURE AND METHODS FOR TREATMENT USING ADOPTIVE CELL THERAPY Cross-Reference to Related Applications [0001] This application claims priority from U.S. provisional application No. 62/514,774, filed June 2, 2017, entitled "ARTICLES OF MANUFACTURE AND METHODS FOR TREATMENT USING ADOPTIVE CELL THERAPY," U.S. provisional application No. 62/515,530, filed June 5, 2017, entitled "ARTICLES OF MANUFACTURE AND METHODS FOR TREATMENT USING ADOPTIVE CELL THERAPY," U.S. provisional application No. 62/521,366, filed June 16, 2017, entitled "ARTICLES OF MANUFACTURE AND METHODS FOR TREATMENT USING ADOPTIVE CELL THERAPY," U.S. provisional application No. 62/527,000, filed June 29, 2017, entitled "ARTICLES OF MANUFACTURE AND METHODS FOR TREATMENT USING ADOPTIVE CELL THERAPY," U.S. provisional application No. 62/549,938, filed August 24, 2017, entitled "ARTICLES OF MANUFACTURE AND METHODS FOR TREATMENT USING ADOPTIVE CELL THERAPY," U.S. provisional application No. 62/580,425, filed November 1, 2017, entitled "ARTICLES OF MANUFACTURE AND METHODS FOR TREATMENT USING ADOPTIVE CELL THERAPY," U.S. provisional application No. 62/593,871, filed December 1, 2017, entitled "ARTICLES OF MANUFACTURE AND METHODS FOR TREATMENT USING ADOPTIVE CELL THERAPY," U.S. provisional application No. 62/596,764, filed December 8, 2017, entitled "ARTICLES OF MANUFACTURE AND METHODS FOR TREATMENT USING ADOPTIVE CELL THERAPY," U.S. provisional application No. 62/614,957, filed January 8, 2018, entitled "ARTICLES OF MANUFACTURE AND METHODS FOR TREATMENT USING ADOPTIVE CELL THERAPY," the contents of which are incorporated by reference in their entirety. Incorporation by Reference of Sequence Listing [0002] The present application is being filed along with a Sequence Listing in electronic format. The Sequence Listing is provided as a file entitled 735042012140SeqList.txt, created June 1, 2018, which is 35,306 bytes in size. The information in the electronic format of the Sequence Listing is incorporated by reference in its entirety. Field [0003] The present disclosure relates in some aspects to adoptive cell therapy involving the administration of doses of cells for treating subjects with disease and conditions such as certain B cell malignancies, and related methods, compositions, uses and articles of manufacture. The cells generally express recombinant receptors such as chimeric antigen receptors (CARs). In some embodiments, the disease or condition is a non-Hodgkin lymphoma (NHL), such as relapsed or refractory NHL or specific NHL subtype; in some embodiments, the subject is of a specific group or subset of NHL subjects, such as heavily pretreated or poor-prognosis subjects. Background [0004] Various immunotherapy and/or cell therapy methods are available for treating diseases and conditions. For example, adoptive cell therapies (including those involving the administration of cells expressing chimeric receptors specific for a disease or disorder of interest, such as chimeric antigen receptors (CARs) and/or other recombinant antigen receptors, as well as other adoptive immune cell and adoptive T cell therapies) can be beneficial in the treatment of cancer or other diseases or disorders. Improved approaches are needed. Provided are methods and uses that meet such needs. Summary [0005] Provided herein are methods, uses, compositions, formulations and articles of manufacture for treating subjects having or suspected of having a disease or condition, such as a cancer or tumor, optionally a B cell malignancy such as NHL or ALL or CLL or a subtype thereof. The methods and other embodiments generally relate to administering to the subject T cells, generally engineered T cells, such as those expressing or containing a recombinant receptor such as a chimeric antigen receptor (CAR) or TCR. [0006] In some embodiments, the dose of cells or cells administered in connection with any embodiments of the provided methods, compositions, articles of manufacture and uses, contains CD4+ T cells or a subtype or phenotype thereof (such as engineered or recombinant receptor- expressing CD4+ T cells) and/or CD8+ T cells or a subtype thereof (such as an engineered or recombinant receptor-expressing CD4+ cells). In some embodiments, the CD8+ cells or subtype or phenotype are present at a particular dose or amount or number; in some embodiments the CD4+ cells or subtype or phenotype are present at a particular dose or amount or number. In some embodiments, the CD8+ cells or subtype or phenotype thereof and the CD4+ cells or subtype or phenotype thereof, are present in the article or composition or combination, or are administered in the methods, at a defined ratio, such as at or about 1:1, or between at or about 1:3 and at or about 3:1. In some embodiments, the dose or administration contains or is of a particular amount or number of one population of the cells and the ratio is a defined ratio or is a naturally-occurring ratio, such as in the blood of the subject from which the cells are derived or ratio that occurs without selection or control for a particular ratio. [0007] In some embodiments, the CD4+ T cells (or subset thereof) and the CD8+ T cells (or subset thereof), individually, contain a receptor that specifically binds to a target antigen expressed by the disease or condition, or a cell or tissue thereof, and/or that is associated with the disease or condition. [0008] In some embodiments, the CD4+ and CD8+ cells are administered and/or formulated together, e.g.
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