CD79b-targeted antibody-drug conjugate (ADC) SHR-A1912 in combination with rituximab, gemcitabine, and oxaliplatin (R-GemOx) in relapsed or refractory (r/r) diffuse large B-cell lymphoma (DLBCL): Data from a phase 1b/2 study.

7013 Background: Patients (pts) with transplant-ineligible r/r DLBCL have an unmet need, with an objective response rate (ORR) of around 40%. CD79b, a key component of the B-cell receptor and expressed in a majority of mature malignancies of B-cell origin, is an attractive therapeutic target for DLBCL. We initiated a phase 1b/2 study to assess the safety and efficacy of SHR-A1912, a novel CD79b-targeted ADC, in combination with chemotherapy in pts with r/r or treatment-naive DLBCL. Here, we report the findings of SHR-A1912 plus R-GemOx regimen in the r/r DLBCL cohort. Methods: The study comprised a dose-escalation (D-ESC) and dose-expansion (D-EXP) phase 1b part and an efficacy-expansion phase 2 part. For the r/r DLBCL cohort, pts who had failed to respond to or had progressed after ≥1 prior anti-cancer therapy were enrolled to receive SHR-A1912 plus R-GemOx (Q3W, IV) for up to 8 cycles, followed by maintenance therapy with SHR-A1912 until disease progression, intolerable toxicity, or investigator decision. The primary endpoints were safety and recommended phase 2 dose (RP2D) in the phase 1b part and ORR in the phase 2 part. Results: As of cutoff date on Nov 19, 2024, 41 pts were enrolled (n=7, 8, and 26 in D-ESC, D-EXP, and phase 2 parts). During D-ESC, DLTs were observed in 2 of the 4 pts receiving 2.7 mg/kg of SHR-A1912 plus R-GemOx (1 with grade 4 decreased platelet count and 1 with grade 3 asthenia and grade 3 decreased appetite); subsequently, 3 pts were given 1.8 mg/kg of SHR-A1912 plus R-GemOx, and no DLTs occurred. 1.8 mg/kg was determined to be the RP2D of SHR-A1912 when combined with R-GemOx. Totally, 37 r/r DLBCL pts received 1.8 mg/kg of SHR-A1912 plus R-GemOx in the study. Grade ≥3 treatment-emergent adverse events occurred in 21 (56.8%) out of the 37 pts, with the most common being hematological toxicities (decreased platelet count, 29.7%; decreased white blood cell count, 24.3%; decreased neutrophil count, 21.6%; anemia, 13.5%; decreased lymphocyte count, 10.8%). Among the 37 pts, 19 achieved a complete response (CR), and 8 achieved a partial response. The ORR was 73.0% (95% CI, 55.9–86.2), and the CR rate was 51.4% (95% CI, 34.4–68.1). 23 (85.2%) of the 27 responders showed an objective response at their first anti-tumor assessment, with a time to response of 1.4 mo (95% CI, 1.2–3.5). All responses were ongoing as of the cutoff date. Conclusions: Inpts with r/r DLBCL, SHR-A1912 at 1.8 mg/kg in combination with R-GemOx was tolerable and demonstrated a safety profile consistent with its individual components. This combination exhibited potent anti-tumor activity, as well as rapid and durable responses. Clinical trial information: NCT06104553 .