Idelalisib Or Venetoclax in R/R CLL Patients Who Failed Prior BTK Inhibitor Therapy (COSMOS Trial) SCAN HERE to LISTEN to STUDY HIGHLIGHTS from the Philipp B

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Publication no: 1754 Primary analysis of anti-CD19 tafasitamab (MOR208) treatment in combination with idelalisib or venetoclax in R/R CLL patients who failed prior BTK inhibitor therapy (COSMOS trial) SCAN HERE TO LISTEN TO STUDY HIGHLIGHTS FROM THE Philipp B. Staber,1* Wojciech Jurczak,2* Wolfram Brugger,3 Asher Chanan-Khan,4 Richard Greil,5 Andrzej Hellmann,6 Maren Dirnberger-Hertweck,7 Peter Kelemen,7 Jan Moritz Middeke,8 Marco Montillo,9 Marina Motta,10 LEAD AUTHOR Talha Munir,11 Peter Neumeister,12 Dietger Niederwieser,13 Sameer A. Parikh,14 Johannes Schetelig,8 Stephan Stilgenbauer,15 Vladan Vucinic,13 Johannes Weirather,3 Jennifer A Woyach,16 Clemens-Martin Wendtner17 *First authors – equally contributed

1Clinical Division of Hematology and Hemostaseology, Department of Internal Medicine I, Vienna General Hospital – Medical University of Vienna, Vienna, Austria; 2Maria Sklodowska Curie Institute, Oncology Centre, Kraków, Poland; 3MorphoSys AG, Planegg, Germany; 4Mayo Clinic Cancer Center, Jacksonville, FL, USA; 5Department of Internal Medicine III with Hematology, Medical Oncology, Hemostaseology, Infectious Diseases, Rheumatology, Oncologic Center, Paracelsus Medical University Salzburg, Salzburg, Austria, and Salzburg Cancer Research Institute and Cancer Cluster, Salzburg, Austria; 6Gdański Uniwersytet Medyczny, Hematology and Transplantology, Gdańsk, Poland; 7MorphoSys AG, Planegg, Germany; 8Medizinische Klinik und Poliklinik I, TU Dresden, Dresden, Germany; 9Niguarda Cancer Center - Niguarda Hospital, Milan, Italy; 10S.C. Ematologia, ASST Spedali Civili, Brescia, Italy; 11Department of Haematology, St James’s University Hospital, Leeds, UK; 12Division of Hematology, Medical University of Graz, Austria; 13Department of Hematology and Medical Oncology, University Hospital, Leipzig, Germany; 14Division of Hematology, Department of Medicine, Mayo Clinic, Rochester, MN, USA; 15Department of Internal Medicine III, Ulm University, Ulm, Germany; 16Division of Hematology, Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA; 17Klinikum Schwabing, Department I of Medicine, Academic Teaching Hospital of University of Munich, Munich, Germany

ASH December 7, 2019: Publication no 1754; Session 642

Cohort B (venetoclax + tafasitamab) (n=13) Background Results • Baseline characteristics for Cohort B are described in Table 3 Conclusions

• Over a quarter of patients with relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL)/ • The primary analysis for both cohorts had a cut-off date of 09 November 2018; here we report Table 3. Baseline characteristics for Cohort B • This study demonstrates that the combinations of tafasitamab with idelalisib or tafasitamab updated results with a cut-off date of 08 October 2019 Characteristic Specification n (%) Characteristic Specification n (%) with venetoclax were generally well tolerated, with promising efficacy in heavily pretreated small lymphocytic lymphoma (SLL) on Bruton’s tyrosine kinase inhibitors (BTKis) are Age (years) Median (range) 64 (50–77) Complex karyotype ≥3 abnormalities 12 (92.3) Sex Female / male 3 (23.1) / 10 (76.9) TP53 Mutated 4 (30.8) patients with R/R CLL who discontinued prior treatment with a BTK inhibitor unresponsive to ibrutinib as a single agent or in combination with CD20-directed treatments Cohort A (idelalisib + tafasitamab) (n=11) Number of prior lines Median (range) 3 (1-5) Abnormal FISH 17 p 13 4 (30.8) such as rituximab,1,2 demonstrating a large unmet need and generating interest in alternative Reason for ibrutinib Progressive disease 10 (77) Del17p and/or TP53 Abnormal/Mutated 5 (38.5) • Baseline characteristics for Cohort A are described in Table 1 discontinuation Toxicity 2 (15.4) BTK Mutated 2 (15.4) • The toxicity profile was distinct and was dependent on the combination partner; however, therapeutic targets IGHV Unmutated 9 (69.2) PLCγ2 Mutated 3 (23.1) the TEAEs in both combinations were manageable 3,4 Table 1. Baseline characteristics for Cohort A • The CD19 antigen is highly conserved at normal to high levels in most B-cell malignancies, Safety • The response rate and durability of response suggest that both combinations are clinically and is associated with lymphomagenesis and increased disease severity;5 therefore, it is a Characteristic Specification n (%) Characteristic Specification n (%) Age (years) Median (range) 69 (51-79) Complex karyotype ≥3 abnormalities 6 (54.5) • Eight (61.5%) patients discontinued treatment during the study due to AEs (23.1%), ICF active in patients with R/R CLL who discontinued prior treatment with a BTK inhibitor promising therapeutic target Sex Female / male 5 (45.5) / 6 (54.5) TP53 Mutated 5 (45.5) Number of prior lines Median (range) 5 (2-9) Abnormal FISH 17 p 13 5 (45.5) withdrawal (15.4%), PD (7.7%), death (7.7%), and other (7.7%) • The response rates and MRD negativity outcomes indicate that combinations of targeted • Tafasitamab is an Fc-enhanced, humanized, CD19-directed monoclonal antibody that has Reason for ibrutinib Progressive disease 9 (81.8) Del17p and/or TP53 Abnormal/Mutated 7 (63.6) discontinuation Toxicity 2 (18.2) BTK Mutated 4 (36.4) • Two patients (15%) permanently discontinued study treatment due to an infusion-related agents with tafasitamab, an anti-CD19 antibody, have valuable antitumor activity enhanced tumor cytotoxicity in CLL compared with non-engineered anti-CD19 analogs, and has IGHV Unmutated 8 (27.7) PLCγ2 Mutated 3 (27.3) reaction (IRR) arising during tafasitamab monotherapy (i.e. before Cycle 1 Day 8) demonstrated safety and a preliminary efficacy in relapsed CLL6 Safety • IRRs could potentially be mitigated by an intra-individual dose ramp-up of tafasitamab (e.g. δ • Idelalisib, a reversible phosphoinositide 3-kinase (PI3K) , and venetoclax, a potent and • Nine (81.8%) patients discontinued treatment during the study due to progressive disease (PD) 1 mg/kg on Day 1, followed by 12 mg/kg on Day 2 of Cycle 1) in patients with high tumor burden selective inhibitor of B-cell lymphoma 2 (BCL2), have been approved by the Food and Drug (36.4%), adverse events (AEs) (18.2%), deaths (18.2%), or physician decision (9.1%) • Neutropenia was the most common Grade ≥3 TEAE (46%), followed by anemia (8%) and Acknowledgments Administration and the European Medicines Agency in combination with the anti-CD20 antibody leukopenia (8%) (Table 4) rituximab in the R/R CLL setting7–10 • Neutropenia was the most common Grade ≥3 treatment-emergent AE (TEAE) (46%), followed by anemia (27%), and thrombocytopenia (27%) (Table 2) • One death occurred in this cohort, which was due to sepsis We thank the patients and their families, clinical researchers, and their teams and hospitals • Two deaths occurred in this cohort (18.2%), one of which was related to disease progression that have participated in this study. This study was sponsored by MorphoSys AG. and the other due to treatment-emergent cardiac failure Table 4. AEs for Cohort B Medical writing support was provided by Ross Jarratt of Syneos Health and funded by n (%), N=13 Study rationale † Preferred term TEAEs* SAEs MorphoSys AG. All grades Grade ≥3 All grades Grade ≥3 Table 2. AEs for Cohort A Hematological Neutropenia 6 (46) 6 (46) 0 0 • This study is being performed to evaluate the safety and preliminary efficacy of tafasitamab in n (%), N=11 † Anemia 5 (39) 1 (8) 1 (8) 1 (8) Preferred term TEAEs* SAEs Leukopenia 3 (23) 1 (8) 0 0 combination with idelalisib, and tafasitamab in combination with venetoclax, in two separate All grades Grade ≥3 All grades Grade ≥3 Febrile neutropenia <20% threshold 1 (8) 1 (8) Disclosures (non-randomized) cohorts Hematological Non-hematological Anemia 7 (64) 3 (27) 1 (9) 1 (9) Infusion-related reaction 7 (54) 2 (15) 2 (15) 2 (15) Neutropenia 5 (46) 5 (46) 0 0 Hyperuricemia 5 (39) 1 (8) 0 0 Thrombocytopenia 4 (36) 3 (27) 1 (9) 1 (9) Nausea 5 (39) 0 0 0 PB Staber – honoraria: Takeda-Millenium, Janssen, Gilead, MSD, Celgene, AbbVie, Roche; membership on an entity’s Board of Directors or Pancytopenia <20% threshold 1 (9) 0 Cough 5 (39) 0 0 0 advisory committees: Takeda-Milleniun, Gilead, Celgene, AbbVie, Roche; research funding: Takeda-Millenium, Roche; speakers bureau: Takeda- Non-hematological Hypophosphatemia 4 (31) 4 (31) 0 0 Millenium, Janssen, Gilead, MSD, AbbVie, Roche. W Jurczak – membership on an entity’s Board of Directors or advisory committees: AstraZeneca, Pyrexia 4 (31) 1 (8) 3 (23) 1 (8) Study design Dyspnea 6 (55) 1 (9) 0 0 Janssen, Loxo, Sandoz; research funding: AstraZeneca, Bayer, Celgene, Celtrion, Gilead, Incyte, Janssen, Loxo, Morphosys, Novo Nordisk, Cough 6 (55) 0 0 0 Pneumonia/lung infection 4 (31) 1 (8) 1 (8) 1 (8) LDH increased 4 (31) 0 0 0 Infusion-related reaction 5 (46) 1 (9) 0 0 Sandoz, RocheServier, Takeda, TG Therapeutics. W Brugger – employment: MorphoSys; shareholder: AstraZeneca. A Chanan-Khan – employment: Fatigue 4 (31) 0 0 0 Mayo Clinic; research funding: Millennium, Ascentage, Janssen, Merck, Pharmacyclics, Xencor, AbbVie. R Greil – consultancy: BMS, Cephalon, Diarrhea 5 (46) 1 (9) 0 0 Dyspepsia 3 (23) 0 0 0 • This was a non-randomized open-label, multicenter, Phase II study (NCT02639910) to evaluate Pyrexia 5 (46) 0 0 0 Vomiting 3 (23) 0 0 0 Amgen, Merck, Novartis, AstraZeneca, Roche, Celgene, Takeda, MSD, AbbVie, Gilead, Daiichi Sankyo; honoraria: BMS, Cephalon, Amgen, Eisai, the safety and efficacy of tafasitamab in combination with either idelalisib (Cohort A) or Urinary tract infection 4 (36) 0 0 0 Dyspnea 3 (23) 0 0 0 Mundipharma, Merck, Janssen-Cliag, Genentech, Novartis, AstraZeneca, BI, Pfizer, Roche, Sanofi Aventis, Celgene, Takeda, MSD, Sandoz, AbbVie, Pneumonia 3 (27) 3 (27) 2 (18) 2 (18) Troponin T increased 3 (23) 0 0 0 Gilead, Daiichi Sankyo; travel/accommodation expenses: BMS, Amgen, Novartis, AstraZeneca, Roche, Celgene, MSD, Gilead; research funding: venetoclax (Cohort B) in patients with R/R CLL previously treated with a BTKi (Figure 1) Upper respiratory tract infection 3 (27) 1 (9) 1 (9) 1 (9) Hypocalcemia 3 (23) 0 0 0 BMS, Cephalon, Amgen, Mundipharma, Merck, Genentech, Novartis, AstraZeneca, Pfizer, Roche, Celgene, GSK, Ratiopharm, Takeda, MSD, Transaminases increased‡ 3 (27) 2 (18) 0 0 Hypokalemia 3 (23) 0 0 0 Study treatment was administered until disease progression, withdrawal of consent, Pleural effusion 3 (27) 0 0 0 Iron deficiency 3 (23) 0 0 0 AbbVie, Gilead. A Hellmann – no disclosures. M Dirnberger-Hertweck – employment: MorphoSys. P Kelemen – employment: MorphoSys. JM • Cardiac failure <20% threshold 1 (9) 1 (9)§ Arthralgia 3 (23) 0 0 0 Middeke – consultancy: Janssen, MSD, Gilead, AbbVie; research funding: Sanofi; speakers bureau: Roche, Sanofi, Janssen, AbbVie. M Montillo Pancreatitis acute <20% threshold 1 (9) 1 (9) Dizziness 3 (23) 0 0 0 unacceptable toxicity, death or patient being lost to follow-up, which ever occurs first Sinusitis 3 (23) 0 0 0 – consultancy: Janssen, Roche, Gilead, AbbVie, AstraZeneca; honoraria: Janssen, Roche, Gilead, AbbVie, AstraZeneca, Acerta; membership on Pulmonary sepsis <20% threshold 1 (9) 1 (9) Skin lesion 3 (23) 0 0 0 an entity’s Board of Directors or advisory committees: Acerta, Versatem; research funding: Roche; speakers bureau: Janssen, Gilead, AbbVie. Patients who had not progressed at the end of the study treatment period (after 24 treatment Bacterial sepsis <20% threshold 1 (9) 1 (9) Sepsis <20% threshold 1 (8) 1 (8)‡ M Mottag – no disclosures. T Munir – consultancy: Sunesis, MorphoSys; honoraria: Janssen, Roche, Gilead, AbbVie, Alexion, Novartis; membership • Septic shock <20% threshold 1 (9) 1 (9) Influenza <20% threshold 1 (8) 1 (8) on an entity’s Board of Directors or advisory committees: Acerta, MorphoSys; other: Pharmacyclics. P Neumeister – no disclosures. D Niederwieser cycles) were permitted to continue with tafasitamab treatment at the Investigator’s discretion Gastroenteritis salmonella <20% threshold 1 (9) 1 (9) Rhinovirus infection <20% threshold 1 (8) 1 (8) Bronchitis <20% threshold 1 (9) 1 (9) Tumor lysis syndrome <20% threshold 1 (8) 1 (8) – no disclosures. SA Parikh – honoraria: AstraZeneca, Pharmacyclics, AbbVie, Genentech; research funding: Janssen, AstraZeneca, Pharmacyclics, Syncope <20% threshold 1 (9) 1 (9) Diarrhea <20% threshold 1 (8) 1 (8) MorphoSys, AbbVie, Acerta Pharma, Ascentage Pharma. J Schetelig – consultancy: AstraZeneca, Janssen, Roche, Gilead, Abbvie, Sanofi, Molmed; Safety Arthralgia <20% threshold 1 (9) 1 (9) Bone pain <20% threshold 1 (8) 1 (8) honoraria: AstraZeneca, Janssen, Roche, Gilead, Abbvie, Sanofi, Novartis; research funding: Genzyme, Sanofi, GSK, Novartis, Abbvi.S Stilgenbauer CRP increased <20% threshold 1 (9) 0 Groin pain <20% threshold 1 (8) 1 (8) – consultancy: Janssen, Roche, Gilead, AbbVie, AstraZeneca, Celgene, GSK, Novartis, MorphoSys; honoraria: Janssen, Roche, Gilead, AbbVie, A safety run-in phase was included, and an independent data monitoring committee supported Squamous cell carcinoma <20% threshold 1 (9) 0 Data cut-off: October 8, 2019. N=13 patients of Cohort B; all patients received at least one dose of tafasitamab. “<20% threshold”, when TEAEs (all grades) occurred in <20% of patients • *Most commonly reported TEAEs (all grades), occurring in ≥20% patients (≥3 out of 13 patients in Cohort B); †All treatment-emergent SAEs reported until data cut-off October 8, 2019; AstraZeneca, Celgene, GSK, Novartis; research funding: Janssen, Roche, Gilead, AbbVie, AstraZeneca, Celgene, GSK, Novartis; speakers bureau: Data cut-off: October 8, 2019. N=11 patients of Cohort A; all patients received at least one dose of tafasitamab. “<20% threshold”, when TEAEs (all grades) occurred in <20% of patients. ‡ the safety evaluations for the first 10 patients who completed ≥1 treatment cycle *Most commonly reported TEAEs (all grades), occurring in ≥20% patients (≥3 out of 11 patients in Cohort A); †All treatment-emergent SAEs reported until data cut-off October 8, 2019; SAE with fatal outcome. AE, adverse event; LDH, lactate dehydrogenase; SAE, serious adverse event; TEAE, treatment-emergent adverse event. Janssen, Roche, Gilead, AbbVie, AstraZeneca, Celgene, GSK, Novartis. V Vucinic – no disclosures; J Weirather – employment: MorphoSys; JA ‡Transaminases increased including alanine aminotransferase increased and/or aspartate aminotransferase increased; §SAE with fatal outcome. Woyach – consultancy: Janssen, Pharmacyclics LLC (an AbbVie Company); research funding: Janssen, Pharmacyclics LLC (an AbbVie Company), AE, adverse event; CRP: C-reactive protein; SAE, serious adverse event; TEAE, treatment-emergent adverse event. Efficacy (Figure 3) AbbVie, Karyopharm, Loxo, MorphoSys, Verastem. C Wendtner – consultancy: Janssen, Roche, Gilead, AbbVie, Mundipharma, MorphoSys; Efficacy Efficacy (Figure 2) • Median time on-study was 15.6 months (95% CI: 0.1–24.9) honoraria: Janssen, Roche, Gilead, AbbVie, Mundipharma, MorphoSys; membership on an entity’s Board of Directors or advisory committees: • Rates of response and progression were determined using modified criteria of the International Janssen, Roche, Gilead, AbbVie, Mundipharma, MorphoSys; travel: Janssen, Roche, Gilead, AbbVie, Mundipharma, MorphoSys; research funding: Median time on-study was 7.4 months (95% CI: 2.1–28.2) Three patients discontinued in the first cycle who did not undergo a response assessment due Janssen, Roche, Gilead, AbbVie, Mundipharma, MorphoSys. Workshop on Chronic Lymphocytic Leukemia for CLL • • • An ORR was achieved in 10/11 (90.9%) patients (complete response [CR] 9.1%, partial response to IRRs or withdrawal of informed consent • Overall response rate (ORR) was determined based on investigator assessment of patient’s [PR] 81.8%) in the intention-to-treat population • An ORR was achieved in 10/13 (76.9%) patients (CR 38.5%, PR 38.5%) in the intention-to-treat clinical and radiological data • Of the eight patients assessed for minimal residual disease (MRD) status, two patients achieved population Correspondence • Computed tomography scans of the neck, chest, abdomen, and pelvis were performed to MRD negativity in the peripheral blood (PB), and 1/3 patients assessed achieved MRD • Of the seven patients assessed for MRD status, six patients achieved MRD negativity in the PB, determine tumor response negativity in the bone marrow (BM) and 2/4 patients assessed achieved MRD negativity in BM Correspondence: [email protected] Figure 1. Study design Figure 2. Time on study and response rate in Cohort A (idelalisib + tafasitamab) Figure 3. Time on study and response rate in Cohort B (venetoclax + tafasitamab)

Reason for Reason for References study treatment CR study treatment PR discontinuation discontinuation CYCLES 1-24 Endpoints CR 1. Byrd JC, et al. Blood 2019;133:2031-42. PR 2. Jain P, et al. Blood 2015;125:2062-7. Other PR COHORT A (n=11) Primary endpoint PD PR 3. Hammer O. mAbs 2012;4:571-7. • AE incidence CR Idelalisib (150 mg BD)* 4. Olejniczak SH, et al. Immunol Invest 2006;35:93–114. and severity PD PR Key inclusion criteria + CR 5. Chung EY, et al. J Clin Invest 2012;122:2257–66. Safety Secondary endpoints tafasitamab (12 mg/kg)† Death* PR 6. Woyach JA, et al. Blood 2014;124:3553-60. run-in CR • R/R CLL patients who • ORR 7. U.S. Food & Drug Administration. Highlights of Prescribing Information (Idelalisib). phase 30-day discontinued prior BTKi • Anti-tafasitamab PD PR Death* PR Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/205858lbl.pdf. safety Last accessed: November 2019. treatment due to antibody formation follow-up AE† CR progression or toxicity AE† PR 8. U.S. Food & Drug Administration. Highlights of Prescribing Information (Venetoclax). • PK analysis for visit Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/208573s009lbl.pdf COHORT B (n=13) ICF withdrawal PR tafasitamab ‡ 2019. Last accessed: November 2019. Best overall response • ECOG performance Death PR SD Best overall response SD Venetoclax 9. European Medicines Agency. Summary of Product Characteristics (Idelalisib). status of 0–2 Exploratory endpoints CR PD PR CR ‡ PD PR Available at: https://www.ema.europa.eu/en/documents/product-information/ (400 mg daily) PR PR • MRD negativity ICF withdrawal NE zydelig-epar-product-information_en.pdf. Last accessed: November 2019. + MRD negativity (blood) MRD negativity (blood) • Mutational status of Physician‘s decision§ PR 10. European Medicines Agency. Summary of Product Characteristics (Venetoclax). tafasitamab (12 mg/kg)† MRD negativity (bone marrow) AE‡ NE MRD negativity (bone marrow) BTK and PLCγ2 Available at: https://www.ema.europa.eu/en/documents/product-information/ ¶ venclyxto-epar-product-information_en.pdf. Last accessed: November 2019. AE SD Ongoing ‡ Ongoing AE NE SCAN HERE TO DOWNLOAD 0 3 6 9 12 15 18 21 24 27 30 0 3 6 9 12 15 18 21 24 27 THE POSTER Time on study (months) Time on study (months) *Idelalisib dosing started on C1D1; †Tafasitamab dosing started on C1D1, was weekly from C1–C3 (with an additional loading dose on C1D4), every second week in C4–C6, and monthly in Copies of this poster obtained through Quick C7–C24; ‡Venetoclax dosing started on C1D8 (20 mg daily for 7 days) followed by a weekly ramp-up (50 mg, 100 mg, 200 mg daily dose). Data cut-off: October 8, 2019. *Heart failure; †Acute iatrogenic pancreatitis; ‡PD with cardiorespiratory failure resulting in death; §Patient reached clinical remission, making them eligible for Data cut-off: October 8, 2019. *Sepsis; †Diarrhea; ‡Infusion-related reactions. AE, adverse event; CR, complete response; ICF, informed consent form; MRD, minimum residual disease; Response (QR) Code are for personal use only and AE, adverse event; BD, twice daily; BTK, Bruton’s tyrosine kinase; BTKi, Bruton’s tyrosine kinase inhibitor; CLL, chronic lymphocytic leukemia; C, cycle; d, day; subsequent transplantation (bridging); ¶Aspartate aminotransferase increased. AE, adverse event; CR, complete response; MRD, minimum residual disease; PD, progressive disease; NE, not evaluable or missing; PD, progressive disease; PR, partial response; SD, stable disease. may not be reproduced without permission from ECOG, Eastern Cooperative Oncology Group; MRD, minimal residual disease; ORR, overall response rate; PK, pharmacokinetic; PLC, phospholipase C; R/R, relapsed/refractory. PR, partial response; SD, stable disease. Note: Time on study (months) was defined as ((date of last documented visit or death – date of first visit) +1) x 0.0328767. Note: Time on study (months) was defined as ((date of last documented visit or death – date of first visit) +1) x 0.0328767. ASH and the author of this poster.

Presented at American Society of Hematology; December 7, 2019; Orlando, FL.