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e14527Background: Currently, numerous antibody-drug conjugates (ADCs) are evaluated for hematologic malignancies with toxic payloads mainly affecting only proliferating cells, and thus resulting in...

8024 Background: CD38 is a type II transmembrane glycoprotein expressed by MM cells. MOR202, a human IgG1 CD38 monoclonal antibody, has shown high single-agent activity in preclinical models of MM and synergy in combination with immunomodulatory drugs (IMiDs), lenalidomide (LEN) and pomalidomide (POM). Methods: This interim analysis of a multicenter phase I/IIa study reports safety and efficacy data from RRMM patient (pt) cohorts treated with clinically relevant doses of MOR202 (2-hour IV infusion; 4, 8 and 16 mg/kg q1w) + Dex (≤40 mg), or at 8 or 16 mg/kg q1w with an IMiD/Dex. Primary objectives were to evaluate the safety, maximum tolerated dose (MTD) and recommended phase II dose of MOR202. Results: As of January 2017, 79 pts had been treated, including 44 in clinically relevant cohorts: 18 received MOR202 + Dex, 15 MOR202 + LEN/Dex and 11 MOR202 + POM/Dex. Pts had received a median of 3, 2 and 3 prior treatment lines, respectively. The MTD of MOR202 was not reached. Combinations were generally well tolerated, with grade ≥3 adverse events (AEs) mainly hematological; 2 pts discontinued due to a MOR202-related AE (one grade 4 thrombocytopenia; one grade 3 acute kidney failure). Infusion-related reactions (all grade 1 or 2) were seen in only 3/44 (7%) pts, and mainly occurred during the first infusion. In the MOR202 + Dex cohort, 5/17 (29%) evaluable pts (receiving at least 1 cycle of treatment) had a response, including 3 with partial responses (PRs) and 2 with very good PRs (VGPRs). Responses were also seen in 11/13 (85%, 8 PRs, 3 VGPRs) evaluable pts in the MOR202 + LEN/Dex cohort and 5/9 (56%, 2 complete responses, 3 PRs) in the MOR202 + POM/Dex cohort. Longest response duration was 17 months (MOR202/Dex). Preliminary analysis showed preservation of high CD38 levels on MM cells under MOR202 therapy. Conclusions: In heavily pretreated pts with RRMM, a 2-hour infusion of MOR202 administered at up to 16 mg/kg with Dex or in combination with an IMiD/Dex, showed a favorable safety profile, including excellent infusion tolerability. Promising preliminary efficacy and long-lasting tumor control was seen. Clinical trial information: NCT01421186.

TPS8066Background: Therapies for multiple myeloma (MM) can slow progression, prolong survival, and reduce symptoms although most patients will relapse. Elotuzumab, a humanized IgG1 immunostimulator...

8012Background: MOR202, a HuCAL-derived, human IgG1 CD38 monoclonal antibody induces ADCC and ADCP as effector functions; preclinical models show high activity of single-agent MOR202 and synergy in...

8574 Background: MOR202 is a HuCAL-derived fully human IgG1 anti-CD38 antibody, with high efficacy in preclinical models of MM. Methods: This is an open-label, dose-escalation study (3 + 3 design) ...

8542 Background: Elotuzumab (Elo) is a humanized anti-CS1monoclonal antibody that enhances natural killer cell mediated antibody dependent cellular cytotoxicity of CS1 expressing myeloma cells. This study included a dose finding Ph I cohort (N=28) and a Ph II cohort (N=73). Here we update Ph II data and provide long term safety data from both cohorts. Methods: Patients (pts) treated with ≥1 (Ph I) or 1–3 (Ph II) prior therapies received Elo + Len/dex as described previously (Lonial JCO 2012; Richardson ASH 2012) until disease progression, unacceptable toxicity, or death. All pts received a premedication regimen including methylprednisolone, diphenhydramine or equivalent, ranitidine or equivalent, and acetaminophen to mitigate infusion reactions. Adverse events (AEs) in Ph I/II pts occurring ≤18 months (mo) (N=98) were compared to AEs with a >18 mo onset in a subgroup of pts treated >18 mo (n=49). This safety analysis excluded 3 Ph I pts treated with Elo 5 mg/kg. Results: In the Ph II cohort (median 63 yr), objective response rate (ORR) was 84%; 92% with 10 mg/kg (n=36) and 76% with 20 mg/kg (n=37). At a median follow-up of 20.8 mo, median progression free survival (PFS) was not reached (10 mg/kg) and 18.6 mo (20 mg/kg). Most common treatment emergent grade ≥3 AEs were lymphopenia (19%), neutropenia (18%), thrombocytopenia (16%) and anemia (14%). Most common grade 3/4 AEs emerging ≤18 vs >18 mo in Ph I/II cohorts are shown (Table). 15 pts discontinued due to AEs; none after 18 mo of treatment. There were 4 second primary malignancies; none were reported after 18 mo. Conclusions: Elo 10 mg/kg + Len/dex was generally well tolerated and resulted in a high ORR and encouraging PFS in pts with RR MM. AEs emergent after 18 mo of therapy were consistent with AEs during the initial 18 mo. Updated Ph II safety/efficacy data and long term safety data from Ph I/II cohorts will be presented.

8020 Background: Elotuzumab (Elo) is a humanized monoclonal IgG1 antibody targeting CS1, a cell surface glycoprotein. CS1 is highly expressed on >95% of multiple myeloma (MM) cells, with lower expression on natural killer cells and little to no expression on normal tissues. A phase 1 trial of Elo plus lenalidomide and low-dose dexamethasone (Elo/Len/Dex) demonstrated an 82% objective response rate (ORR) in patients (pts) with relapsed/refractory (RR) MM (Lonial et al. J Clin Oncol, in press). Methods: In this phase 2 study, previously treated pts with MM were randomized to Elo 10 or 20 mg/kg IV (days 1, 8, 15, and 22 every 28-days in first 2 cycles and days 1 and 15 of subsequent cycles), Len 25 mg PO (days 1-21) and Dex 40 mg PO weekly. Prophylaxis for infusion-related reactions (IRs) was administered prior to each Elo infusion. Treatment continued until disease progression or unacceptable toxicity. The primary objective was to assess efficacy (ORR ≥partial response [PR]) according to IMWG criteria. Results: Among73 pts (median age 63 years; range, 39-82), 55% had received ≥2 prior therapies, 60% had received prior bortezomib, and 62% prior thalidomide. ORR was 82% for all pts including 48% ≥ very good PR (VGPR). The ORRs were 92% in the 10 mg/kg group (n=36) and 73% in the 20 mg/kg group (n=37). Median time to best response was 2.2 months (range, 0.7-17.5). After a median follow-up of 14.1 months, median progression-free survival (PFS) has not been reached, with PFS rates of 75% (10 mg/kg) and 65% (20 mg/kg). Elo/Len/Dex also showed encouraging activity in pts with high-risk cytogenetics (ORR 80%) and/or Stage 2-3 MM (ORR 81%). The most common grade 3/4 toxicities were neutropenia (16%), lymphopenia (16%), and thrombocytopenia (16%). Investigator-designated IRs were reported in 12% of pts (all grades); 1 pt (1.4%) had grade 3 IR (rash). Conclusions: Elo/Len/Dex was generally well tolerated and resulted in a high ORR, and PFS not reached after 14.1 months of median follow-up in pts with RR MM. Updated results will be presented at the meeting. Two phase 3 trials of 10 mg/kg Elo/Len/Dex are ongoing in newly diagnosed MM (ELOQUENT1; CA204-006; NCT01335399) and RR MM (ELOQUENT2; CA204-004; NCT01239797).