At data cutoff on May 31, 2022, 70 pts have received IV ALNUC, 39% (27/70) achieved an objective response, and median progression-free survival was 13.3 wks (95% CI, 8.1–23.9). Median DOR in pts achieving a response with IV ALNUC was 146.1 wks (95% CI, 40.6–not reached).

Forty-seven pts were treated with SC ALNUC in dose escalation (10 mg: n = 6; 15 mg: n = 4; 30 mg: n = 6; 60 mg: n = 3) and dose expansion (10 mg: n = 19; 30 mg: n = 9). Median age was 63 yrs; 55% were female. Pts received a median of 4 prior regimens; 98% had myeloma refractory to the last LOT, 96%/62% had triple-class exposed/refractory myeloma, and 60%/21% had penta-drug exposed/refractory myeloma. At the May 31, 2022 data cutoff, median duration of follow-up was 2.6 mo (range, 0–11.4), and 68% (n = 32) of pts were continuing SC ALNUC treatment.

Any-grade/grade 3–4 treatment-emergent adverse events occurred in 89%/62% of treated pts; the most common were CRS (53%/0%), neutropenia (34%/30%), and anemia (34%/17%). All CRS events were limited to grade 1 (21 pts; 45%) or grade 2 (4 pts; 9%); 20 pts received ≥ 1 concomitant medication for CRS, including tocilizumab (n = 12) and/or corticosteroids (n = 8). Median time to CRS onset was 3 d (range, 1–20); median duration was 2 d (range, 1–11). In 16 pts with grade 3–4 neutropenia, median time to resolution (grade ≤ 2) was 6 d (range, 1–36). There was one grade 1 immune effector cell-associated neurotoxicity event. No pts discontinued treatment due to adverse events; no treatment-related deaths occurred.

Preliminary population pharmacokinetic analysis estimated SC ALNUC bioavailability of ~70%; 30 mg SC achieved similar concentrations observed with 10 mg IV Cmax by end of C1; baseline body weight was not a significant covariate of exposure. Hallmark pharmacodynamic effects of TCEs were observed with SC and IV ALNUC (peripheral blood immune cell redistribution, transient cytokine release, and induction of T-cell factors associated with antitumor activity).

Among 41 efficacy-evaluable (EE) pts treated with SC ALNUC (received ≥ 1 dose and had ≥ 1 post-baseline disease assessment), ORR was 51% (21/41 pts) across all dosing regimens and 77% (10/13 pts) in pts receiving target doses ≥ 30 mg (Figure). Among the 21 pts who achieved a response, 14 pts had evaluable MRD samples, and all (100%) were MRD negative (10-5 sensitivity) at C2D1 or C4D1. Median time to response was 4.3 wks (range, 4.1–17.4), and all 21 responses (100%) were ongoing.

At data cutoff on May 31, 2022, 70 pts have received IV ALNUC, 39% (27/70) achieved an objective response, and median progression-free survival was 13.3 wks (95% CI, 8.1–23.9). Median DOR in pts achieving a response with IV ALNUC was 146.1 wks (95% CI, 40.6–not reached).

Forty-seven pts were treated with SC ALNUC in dose escalation (10 mg: n = 6; 15 mg: n = 4; 30 mg: n = 6; 60 mg: n = 3) and dose expansion (10 mg: n = 19; 30 mg: n = 9). Median age was 63 yrs; 55% were female. Pts received a median of 4 prior regimens; 98% had myeloma refractory to the last LOT, 96%/62% had triple-class exposed/refractory myeloma, and 60%/21% had penta-drug exposed/refractory myeloma. At the May 31, 2022 data cutoff, median duration of follow-up was 2.6 mo (range, 0–11.4), and 68% (n = 32) of pts were continuing SC ALNUC treatment.

Any-grade/grade 3–4 treatment-emergent adverse events occurred in 89%/62% of treated pts; the most common were CRS (53%/0%), neutropenia (34%/30%), and anemia (34%/17%). All CRS events were limited to grade 1 (21 pts; 45%) or grade 2 (4 pts; 9%); 20 pts received ≥ 1 concomitant medication for CRS, including tocilizumab (n = 12) and/or corticosteroids (n = 8). Median time to CRS onset was 3 d (range, 1–20); median duration was 2 d (range, 1–11). In 16 pts with grade 3–4 neutropenia, median time to resolution (grade ≤ 2) was 6 d (range, 1–36). There was one grade 1 immune effector cell-associated neurotoxicity event. No pts discontinued treatment due to adverse events; no treatment-related deaths occurred.

Preliminary population pharmacokinetic analysis estimated SC ALNUC bioavailability of ~70%; 30 mg SC achieved similar concentrations observed with 10 mg IV Cmax by end of C1; baseline body weight was not a significant covariate of exposure. Hallmark pharmacodynamic effects of TCEs were observed with SC and IV ALNUC (peripheral blood immune cell redistribution, transient cytokine release, and induction of T-cell factors associated with antitumor activity).

Among 41 efficacy-evaluable (EE) pts treated with SC ALNUC (received ≥ 1 dose and had ≥ 1 post-baseline disease assessment), ORR was 51% (21/41 pts) across all dosing regimens and 77% (10/13 pts) in pts receiving target doses ≥ 30 mg (Figure). Among the 21 pts who achieved a response, 14 pts had evaluable MRD samples, and all (100%) were MRD negative (10-5 sensitivity) at C2D1 or C4D1. Median time to response was 4.3 wks (range, 4.1–17.4), and all 21 responses (100%) were ongoing.

• The overall response rate (ORR) in all patients was 43.3% with a stringent complete response/complete response (sCR/CR) of 16.7%
• The likelihood of response was dose-dependent. ORR by CC-93269 dose:
  • Dose ≤ 3mg (n= 7): 0%
  • Dose 3 to 6 mg or fixed-dose 6 mg (n= 14): 7%
  • Dose 6 to 10 mg or fixed-dose 10 mg (n= 9): 88.9%
• Among the nine patients treated with 10 mg of CC-93269, the ORR was 88.9% with a sCR/CR of 44.4%
• The median time to response was 4.1 weeks (range; 4–13.1)
• Among 13 responding patients, 11 responses are ongoing
• Measurable residual disease (MRD) negativity was achieved by 12 of the 13 responding patients