Mayer, L

e19057 Background: In ELM-2 (NCT03888105), a Ph 2, single arm, open label trial, odronextamab demonstrated robust efficacy, generally manageable safety, and overall maintenance of patient-reported outcomes (PROs) in R/R FL pts (Villasboas et al. ASH 2023). In FL, pts with disease progression within 2 yrs of frontline chemoimmunotherapy (POD24) are hard to treat with poor clinical outcomes, representing an unmet need. We report PROs by POD24 status in pts with Grade 1–3a R/R FL from ELM-2. Methods: Pts received IV odronextamab in 21-day cycles (C): 80 mg QW in C1–4, with C1 dose step up to mitigate cytokine release syndrome, then 160 mg Q2W (Q4W if complete response ≥9 mo) until progression. PROs were collected at baseline (BL), Wks 2–4, 10, then Q8W in Yr 1, and Q12W in Yr 2. Post-hoc POD24 subgroup analyses were performed on six EORTC QLQ-C30 scales, the EQ-5D-3L VAS, and FACT-Lym LymS. Estimated mean change from BL (CFB) was analyzed using mixed models for repeated measures (MMRM) through Wk 42 (≥10 pts at last assessment). Published meaningful CFB thresholds were used to define deterioration/improvement in responder analyses. Results: By Jan 31, 2023, 140 pts with R/R FL had received odronextamab. Pts with POD24 (n=70) were younger than pts without POD24 (n=70; median age 57.5 vs 62.0 y), had fewer prior Tx lines (median 2 vs 3), and a higher proportion double refractory to anti-CD20 Ab + alkylator (53% vs 29%). Objective response rate was similar in evaluable pts with (n=63; 79%) and without (n=65; 80%) POD24. PRO questionnaire completion ranged from 52–95% through Wk 42 across groups. Descriptive analyses suggest BL PRO scores were similar by POD24 status, showing good HRQoL/functioning and low symptom burden, and were generally maintained through Wk 42 with minimal between-group differences (overlapping 95% CIs for LS mean CFB [Table]). In both groups, more pts reported PRO maintenance or improvement vs deterioration across visits, except for fatigue at Wk 10 in pts without POD24. Conclusions: In pts with heavily pretreated R/R FL, odronextamab Tx maintained HRQoL, functioning, and symptoms irrespective of POD24 status. Clinical trial information: NCT03888105 . [Table: see text]

Abstract Background: R/R FL is an incurable disease and outcomes worsen with successive relapses. A high unmet need remains for therapies that improve tumor control and extend survival after relapse. Odronextamab, an off-the-shelf CD20×CD3 bispecific antibody, demonstrated compelling efficacy, generally manageable safety, and maintenance of pt-reported overall quality of life scores from baseline in an interim analysis of the ELM-2 study (NCT03888105) in heavily pretreated pts with R/R FL (Villasboas et al. ASH 2023). Here, for the first time, we present the primary analysis of R/R FL in ELM-2. Methods: IV odronextamab was administered in 21-day cycles (C) until disease progression/unacceptable toxicity. Steroid prophylaxis and step-up dosing (0.7/4/20 mg) were used in C1 to mitigate the risk of cytokine release syndrome (CRS), followed by 80 mg on Days (D) 1, 8, and 15 of C2-4. Maintenance dosing continued at 160 mg Q2W, or Q4W if complete response (CR) was durable for 9 months (mo). Primary endpoint was objective response rate (ORR) per Lugano criteria by independent central review (ICR). Secondary endpoints included CR rate, duration of response (DOR), progression-free survival (PFS), and overall survival (OS). Primary analysis was performed when 128 pts had ≥52 weeks’ follow-up. Results: At data cutoff (Oct 20, 2023), 128 pts with FL Grade (Gr) 1-3a were evaluable for efficacy and safety: median age 61 yrs (range 22-84); FLIPI risk score 3-5 57.8%; POD24 49.2%; median 3 prior lines of therapy (2-13); 71.9% refractory to last treatment (Tx); 74.2% refractory to an anti-CD20 antibody. The median no. of Tx cycles was 19.4 (0.1-95.9); 95.3% and 85.2% of pts completed C1 and C4, respectively.Median efficacy follow-up was 20.1 mo; ORR was 80.5% and CR rate was 73.4% confirmed by ICR. Responses were durable (median DOR 22.6 mo; median DOCR 25.1 mo). Median PFS was 20.7 mo and 24-mo PFS was 46.1%. Median OS was not reached and 24-mo OS was 70.1%.The odronextamab safety profile was generally manageable and consistent with previous reports. Tx-emergent adverse events (AEs) occurred in all pts (Gr ≥3 85.9%); 15.6% had AEs leading to Tx discontinuation. With 0.7/4/20 mg step up (n=60), CRS events were mostly low grade (Gr 1 45.0%; Gr 2 10.0%; Gr 3 in 1 pt), occurred mostly in C1, and resolved in a median of 2 days; ICANS was reported in 1 pt (Gr 2). Infection rates were consistent with heavily pretreated, immunosuppressed pts (Leonard et al. JCO 2019; Hayne et al. BBMT 2020), occurring in 79.7% (102/128) of pts (Gr 4/5 14.0%; COVID-19 36.7% [Gr 5 6.3%]).Conclusion: Odronextamab demonstrated deep and durable responses in heavily pretreated pts with R/R FL; 91% of responders achieved CR, correlating with favorable PFS and OS at 24 mo. Odronextamab had a generally manageable safety profile and a low incidence of Gr 3 CRS/ICANS. Odronextamab could offer an important off-the-shelf Tx option for pts with heavily pretreated R/R FL. Citation Format: Geoffrey Chong, Michal Taszner, Silvana Novelli, Seok-Goo Cho, Jose C. Villasboas, Ana Jiménez Ubieto, Benoît Tessoulin, Michelle Poon, David Tucker, Jan Walewski, Yuqin Song, Emmanuel Bachy, Stephanie Guidez, Aranzazu Alonso, Deepa Jagadeesh, Stefano Luminari, Laura Magnano Mayer, Elżbieta Iskierka-Jażdżewska, Monica Tani, Jingxian Cai, Amulya Uppala, Saleem Shariff, Jurriaan Brouwer-Visser, Aafia Chaudhry, Hesham Mohamed, Srikanth Ambati, Tae Min Kim. Primary analysis of the Phase 2 ELM-2 study: Odronextamab in patients (pts) with relapsed/refractory follicular lymphoma (R/R FL) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT243.