MMAE disrupts cell division and triggers apoptosis. Pola binds to cell surface antigen CD79b. Pola is internalized; linker cleaves, releasing MMAE

Transcription

1 Adding Polatuzumab Vedotin (Pola) to Bendamustine and Rituximab () Treatment Improves Survival in Patients With Relapsed/Refractory DLBCL: Results of a Phase II Clinical Trial Abstract S802 Sehn LH, Kamdar M, Herrera AF, McMillan A, Flowers C, Kim WS, Kim TM, Ozcan M, Trněný M, Demeter J, Hertzberg M, Salles G, Davies A, Hirata J, Cheng J, Ku G, and Matasar M

2 Background Polatuzumab vedotin (pola) is an antibody-drug conjugate (ADC) targeting CD79b expressed in follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL) Safety run-in phase Ib portion of the study showed promising objective response rate (ORR) with pola plus bendamustine and rituximab (pola-) in heavily pretreated relapsed/refractory (R/R) FL and DLBCL (ORR 100% and 50%, respectively) 1 Here we report safety and efficacy results from the phase II randomized cohorts ( vs pola-) Pola binds to cell surface antigen CD79b Pola is internalized; linker cleaves, releasing MMAE MMAE disrupts cell division and triggers apoptosis MMAE, monomethyl auristatin E 1. Matasar M, et al. Hematologica. 2017;35(s2):

3 Phase II Study Design 1:1 Randomization R/R FL N = 80 R/R DLBCL N = 80 Pola- Pola- Stratification DOR 12 months vs >12 months High vs low disease burden DOR 12 months vs >12 months Schedule FL: 28-day cycles 6 DLBCL: 21-day cycles 6 Pola (1.8 mg/kg IV 1 day); (90 mg/m 2 IV 2 days); rituximab (375 mg/m 2 IV 1 day) Primary endpoint PET-CR* by IRC, 6 weeks to 8 weeks post end of treatment (EOT) *Modified Lugano 2014 criteria: PET-CR requires negative bone marrow; PET-PR required CT criteria be met CT, chemotherapy; DOR, duration of response; IRC, independent review committee ; PET-CR, positive emission tomography complete response

4 Key Inclusion/Exclusion Criteria Inclusion Age 18 R/R FL (grade 1, 2, 3a) or DLBCL At least 1 bidimensionally measureable lesion 1.5 cm in its longest dimension ECOG PS 0-2 Adequate hematologic function If received prior bendamustine, response duration must have been >1 year Exclusion Prior allogeneic stem cell transplant Autologous stem cell transplant within 100 days prior to cycle 1 day 1 History of transformation of indolent disease to DLBCL Current grade >1 peripheral neuropathy Eligible for autologous transplant if DLBCL ECOG PS, Eastern Cooperative Oncology Group performance status

5 Disposition: DLBCL R/R DLBCL N = 80 (N = 40) Pola- (N = 40) Not treated (N = 1) Not treated (N = 1) Treated (N = 39) Treated (N = 39) Off Study (N = 32) Death (n = 25) AE (n = 7) PD (n = 18) Study withdrawal (n = 7) Off Study (N = 20) Death (n = 17) AE (n = 7) PD (n = 10) Study withdrawal (n = 3) Alive in follow-up (N = 7) Alive in follow-up (N = 19) Median follow-up: 10.9 months 11.1 months Data Cut-Off: 3 May 17 AE, adverse event; PD, progressive disease

6 Baseline Characteristics: DLBCL (N = 40) Pola- (N = 40) Median age, years (range) 71 (30-84) 67 (33-86) Male, n (%) 25 (63) 28 (70) Baseline ECOG PS, n (%) (78) 8 (20) 33 (83) 6 (15) Stage III/IV disease, n (%) 36 (90) 34 (85) IPI 3 at enrollment, n (%) 29 (73) 22 (55) Has bulky disease ( 7.5 cm), n (%) 15 (38) 10 (25) Has extranodal disease, n (%) 29 (73) 27 (68) Stratification factor, n (%) DOR of last treatment 12 months 33 (83) 32 (80) IPI, International Prognostic Index

7 Baseline Characteristics: DLBCL (N = 40) Pola- (N = 40) Lines of prior treatment, median (range) 2 (1-5) 2 (1-7) Prior bone marrow transplant, n (%) 6 (15) 9 (23) Prior bendamustine, n (%) - 1 (3) Prior anti-cd20 agent, n (%) 39 (98) 39 (98) Refractory, n (%) Last prior therapy* Primary refractory *No response or progression within 6 months of last treatment 33 (83) 28 (70) 30 (75) 20 (50)

8 Grade 3-5 Adverse Events ( 10% By Preferred Term) Hematological, n (%) Neutropenia Febrile neutropenia Thrombocytopenia Anemia Nonhematological, n (%) Infections (SOC) Peripheral neuropathy* *Peripheral neuropathy reported by MedRA SMQ (Standardized MedRa Query) (N = 80) 21 (26) 4 (5) 12 (15) 5 (6) 13 (16) 0 Pola- (N = 77) 31 (40) 9 (12) 14 (18) 14 (18) 15 (19) 1 (1) In pola-, peripheral neuropathy was mostly grade 1 (25%) and 2 (13%), and mostly reversible Grade 5 rates were similar between treatment arms ( 11%, pola- 12%) SOC, system organ class

9 DLBCL: Significantly Higher PET-CR With Pola- Response at EOT (IRC)* Best Overall Response (INV) % Patients P = OR P = CR % Patients BOR CR 58 Pola- Pola- *Primary endpoint Note: EOT IRC and INV assessments were highly concordant (>90%) BOR, best overall response; CR, complete response; INV, investigator; IRC, independent review committee

10 Conclusions Pola can be safely administered in combination with DLBCL: Adding pola to significantly improved response rates, PFS, and OS regardless of prior lines of treatment or refractoriness Pola received Breakthrough Therapy Designation (BTD) and Priority Medicines (PRIME) designation by the FDA and EMA for R/R DLBCL

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