Asmus, Erik

7514 Background: Iberdomide (Iber) is a CELMoD that binds with greater specificity & affinity to the cereblon protein of the E3 ligase complex than a traditional IMiD. Both transplant-eligible (TE) & ineligible (TIE) patients (pts) with newly diagnosed multiple myeloma (NDMM) are currently treated with quadruplet induction, consisting of an anti-CD38 monoclonal antibody, a proteasome inhibitor, an IMiD & dexamethasone (dex). We conducted a clinical trial (NCT05392946, IDEAL) to examine the efficacy of a novel finite-duration approach, using Iber, daratumumab, bortezomib & dex (Iber-DVd) quadruplet induction followed by Iber monotherapy maintenance. Methods: Both TE and TIE pts with NDMM were enrolled in this Phase 1 (3+3 design)/Phase 2 (single stage) trial. The primary goal was to assess the ≥complete response (CR) rate — utilizing the more sensitive serum MASS-FIX assay in lieu of serum immunofixation — during induction. Treatment involved twelve 28-day cycles of induction with Iber, given PO at the recommended phase 2 dose (RP2D), days 1-21, daratumumab 1800mg SQ, weekly for 2 cycles, every other week during Cycles 3-6, & every 4 weeks thereafter, bortezomib 1.3 mg/m 2 SQ, weekly & dex 40 mg, weekly, followed by Iber monotherapy (24 cycles). Growth factor was not allowed during the dose-limiting toxicity (DLT) assessment period (Cycle 1). Results: Among 47 pts enrolled, 9 pts were in Phase 1 portion which assessed the maximum tolerated dose (MTD), with Iber starting at 1 mg/day dose, days 1-21 [Dose Level (DL) 1]. DLT (all grade 4 neutropenia) was noted in 3 pts, 2 at DL 1 & 1 at DL -1. This analysis includes 44 pts who received Iber at the RP2D (0.75 mg/day, days 1-21), including 6 pts from the Dose Confirmation Cohort (Phase 1, DL -1), dosed at MTD, & 38 pts in the Dose Expansion Cohort. The median age at registration was 65 years (range 36-86 years), & 23 pts (52.3%) were deemed high-risk. At data cut-off, pts had received a median of 15 cycles (range 3-36) of therapy. Overall response rate was 100%; ≥CR rate, 36.4% (95% CI: 22.4, 52.2) during induction & 52.3% (95% CI: 36.7, 67.5), overall, including the maintenance phase. The marrow flow-based (10 -5 ) MRD negative rate was 29.5% during induction & 47.7% overall. At a median follow-up (FU) 18.3 mos, 2 pts have died (one during FU due to progressive disease & the other on-treatment due to COVID-19). 12- (& 18-) month progression-free survival & overall survival rates were 91% (88%) & 97% (94%), respectively. Most common toxicities at RP2D were lymphopenia, neutropenia (leading 27% of pts to require pegfilgrastim support), rash, peripheral neuropathy, diarrhea, & infections. Cases of high-grade fatigue were low (<5%). Updated data will be presented at the meeting. Conclusions: Iber-DVd is an active and safe regimen for both TE and TIE pts with NDMM, leading to high response rates which improved over time, with nearly one-half of the pts achieving MRD negative state. Clinical trial information: NCT05392946 .

6123 Background: Pemetrexed (PTX) is safe and tolerable with responses reported in pts with R/M SGC. Given enhanced responses with PTX and pembrolizumab (PMB) for lung cancer, we hypothesized that PTX and PMB will have activity for SGC. Herein we present the efficacy results in pts with adenoid cystic carcinoma (ACC). Methods: MC200708 is a single arm phase II study of PTX and PMB in pts with R/M SGC (NCT04895735) with 2 cohorts: ACC (cohort A) and non-ACC (cohort B). Key eligibility criteria: ≥18 years, ECOG 0-1, measurable disease. Prior ICI and/or PTX was allowed. Key exclusion criteria: serious comorbidities, autoimmune disease and brain metastases. Simon’s 2-stage design was used for each cohort. Primary endpoint was overall response rate (ORR) for Cohort A but was amended to clinical benefit rate (CBR=SD+PR+CR) due to prolonged SD in several pts. Secondary endpoints: progression free survival (PFS), overall survival (OS), and toxicity. Exploratory analyses in Cohort A1 (post-amendment pts) included PSMA PET imaging and circulating PSMA extravesicles (EVs) as a biomarker. All pts received PTX 500 mg/m2 IV + PMB 200 mg IV q3 weeks until progression or treatment intolerance. Imaging was q3 cycles. Results: 20 pts (11 Cohort A + 9 Cohort A1) were enrolled from August 2021-Feb 2025. All 20 patients were eligible and received ≥ 1 cycle of treatment. Median age was 60.5 yrs, 50% male, performance status 0 (80%) or 1 (20%). 11 pts had no prior therapies (55.0%). The remaining pts had 1 (35%) or 2 (10%) prior lines of therapy. 75% of pts had no prior ICI. In Cohort A, the ORR was 0% (0 of 11). Cohort A1 met criteria for success based on CBR with 1 PR (12.5%) and 5 SD (62.5%) in the first 8 pts. For the whole cohort of 20 patients, the ORR was 5% (95% CI: 0.1-24.9) and the CBR rate was 75% (95% CI: 51-91) with 1 PR and 14 pts with SD. The duration of response for the 1 PR patient was 12.4 months. The median duration of response for the 15 pts with SD was 7.5 (2.0-29.7) months. 3 pts (15%) had PD and 2 pts (10%) went off prior to response assessment. Median cycles of treatment was 4 (2-30). In the 17 pts who discontinued, treatment was stopped in 9 (53%) for PD, 4 (23.5%) due to adverse events (AE), and 4 (23.5%) due to physician/patient preference. With a median follow-up of 14.5 months (1.5-39.2), the 1-year PFS rate is 52.1% (32.6 – 83.2%) and the OS rate is 82.1% (95% CI: 65.6 – 100%). The overall grade 3+ AE rate regardless of attribution was 80% (16/20). The most common grade 3 AEs were lymphocyte count decrease (40%), hypertension (20%), fatigue (10%), and pneumonitis (10%). 2 pts had a grade 4 AE (lymphocyte count decrease and thrombotic thrombocytopenic purpura). There were no treatment-related deaths. Analysis of correlative studies for Cohort A1 with PSMA imaging and EV biomarker ongoing. Conclusions: PTX and PMB has modest activity in pts with R/M ACC with CBR of 75% and prolonged benefit for some patients. Clinical trial information: NCT04895735 .