BRCR Global (United States)

3000 Background: DB-1310 is a novel ADC comprised of a humanized anti-HER3 IgG1 monoclonal antibody, cleavable peptide linker, and DNA topoisomerase I inhibitor. Here, we report the preliminary results of the FIH trial. Methods: This global, multi-center, open-label Ph 1/2a trial includes dose escalation and expansion. Pts with advanced solid tumors who had failed standard therapy were enrolled. In Ph1, DB-1310 was planned to be administered at doses from 1.5 mg/kg to 6.5 mg/kg, Q3W, iv, using a 3+3 design, with additional pts enrolled to determine the RP2D. Ph 2a will include approximately 30-40 pts per cohort to optimize the RP2D and assess efficacy. Results: As of Jan 17, 2025, 123 pts were enrolled and treated with DB-1310 monotherapy in Ph1 (ECOG PS 1, 80.5%; White, 39.0%, Asian, 52.8%; NSCLC, 65.0%, EGFRm NSCLC, 37.4%; brain metastasis, 17.1%), median prior lines of systemic therapy was 3 (range, 1-11). Of the 42 efficacy-evaluable pts with EGFRm NSCLC, 92.9% had previously received 3 rd generation EGFR TKI, 92.9% had received platinum-based chemotherapy. The unconfirmed ORR was 25.5% (95% CI, 17.63, 34.65) across all tumor types and 35.7% (95% CI, 21.55, 51.97) in EGFRm NSCLC. Median PFS was 5.4 months overall and 7.0 months for EGFRm NSCLC. 38 (30.9%) pts experienced ≥ G3 TRAEs, while 7 (5.7%) had drug-related SAEs. TRAEs led to dose reduction in 14 (11.4%) pts and discontinuation in 5 (4.1%) pts. No TRAE leading to death was reported. Most common TRAE ( > 20%, any grade/≥G3) were nausea (36.6%/0.8%), anemia (35.8%/4.1%), neutrophil count decreased (34.1%/17.9%), platelet count decreased (31.7%/9.8%), white blood cell count decreased (29.3%/8.9%), decreased appetite (23.6%/0.8%), and vomiting (21.1%/0%). Interstitial lung disease occurred in 7 pts (5.7%, 6 G1 and 1 G2). PK exposure was increased through dose escalation, with low systemic payload exposure and no accumulation of DB-1310 upon repeated administration. Conclusions: DB-1310 showed a manageable safety profile and encouraging antitumor activity in pts with heavily pretreated advanced solid tumors, particularly EGFRm NSCLC. Clinical trial information: NCT05785741 . Tumor response by dose (efficacy-evaluable). Dose (mg/kg) 1.5 3 4.5 5.0 5.5 6 Total All tumors, n 3 10 25 53 16 3 110 uORR, n (%) (95% CI) 0 (0)(0.00, 70.76) 1(10.0)(0.25, 44.50) 8 (32.0)(14.95, 53.50) 13 (24.5) (13.76, 38.28) 6 (37.5) (15.20, 64.57) 0 (0)(0.00, 70.76) 28 (25.5) (17.63, 34.65) DCR, n (%) (95% CI) 3 (100.0)(29.24, 100.00) 8 (80.0)(44.39, 97.48) 23 (92.0)(73.97, 99.02) 42 (79.2) (65.89, 89.16) 11 (68.8) (41.34, 88.98) 2 (66.7) (9.43, 99.16) 89 (80.9) (72.31, 87.78%) EGFRm NSCLC, n 0 7 9 16 8 2 42 uORR, n (%) (95% CI) - 1 (14.3)(0.36, 57.87) 4 (44.4) (13.70, 78.80) 5 (31.3) (11.02, 58.66) 5 (62.5) (24.49, 91.48) 0 (0)(0.00, 84.19) 15 (35.7) (21.55, 51.97) DCR, n (%) (95% CI) - 6 (85.7) (42.13, 99.64) 9 (100.0) (66.37, 100.00) 14 (87.5) (61.65, 98.45) 7 (87.5) (47.35, 99.68) 2 (100.0)(15.81, 100.00) 38 (90.5) (77.38, 97.34)

Historically, treatment for hereditary angioedema (HAE) attacks has been administered by healthcare professionals (HCPs). Patient self-administration could reduce delays between symptom onset and treatment, and attack burden. The primary objective was to assess the safety of self-administered icatibant in patients with HAE type I or II. Secondary objectives included patient convenience and clinical efficacy of self-administration. In this phase IIIb, open-label, multicenter study, adult patients were trained to self-administer a single 30-mg icatibant subcutaneous injection to treat their next attack. Icatibant-naïve patients were treated by an HCP prior to self-administration. Evaluations included adverse event (AE) reporting, a validated questionnaire for convenience, and visual analog scale for efficacy. A total of 151 patients were enrolled; 104 had an attack requiring treatment during the study, and 97 patients (19 naïve) were included in the self-administration cohort. Recurrence or worsening of HAE symptoms (22 of 97) was the most commonly reported AE; rescue medications including icatibant (N = 3) and C1-inhibitor concentrate (N = 6) were used in 13 cases. Overall, 89 of 97 patients used a single injection of icatibant. No serious AEs or hospitalizations were reported. Most patients (91.7%) found self-administration preferable to administration in the clinic. The median time to symptom relief (3.8 h) was comparable with results from controlled trials of icatibant. With appropriate training, patients were successfully able to recognize HAE attacks and decide when to self-administer icatibant. This, coupled with the patient-reported high degree of satisfaction, convenience and ease of use supports the adoption of icatibant self-administration in clinical practice.