Session: 623. Mantle Cell, Follicular, Waldenstrom’s, and Other Indolent B Cell Lymphomas: Clinical and Epidemiological: Poster I
Hematology Disease Topics & Pathways:
Research, Clinical trials, Clinical Research
Methods: Eligible patients with r/r CD20-positive B-NHL were enrolled in this open-label, multicenter phase I trial (NCT05805943). IMM0306 was administered as at escalating doses of 0.04, 0.1, 0.25, 0.5, 0.8, 1.2, 1.6, 2.0 mg/kg intravenously once a week after a 2-week single-dose observation period, until disease progression or intolerable toxicity. The primary objective is to evaluate the safety, tolerability, and to determine the recommended dose for Phase Ⅱ trial (RP2D). The secondary objective is to evaluate the preliminary efficacy, PK and the immunogenicity of IMM0306. Dose-limiting toxicity (DLT) was evaluated in the first 28 days. Safety was evaluated per CTCAE version 5.0, tumor assessments were performed every 8 weeks by Lugano 2014.
Results: As of Apr 18, 2024, 48 patients were enrolled. The median age was 56 years old with 30 (62.5%) males. 33 (68.8%) patients had ECOG PS ≥ 1. The median number of prior lines of therapy was 3. All patients received previous anti-CD20 treatment. Among the 33 efficacy evaluable patients who received doses of 0.8-2.0 mg/kg, the overall response rate (ORR) was 30.3% (10/33), including 15.2% (5/33) complete response (CR) and 15.2% (5/33) partial response (PR); Among 17 efficacy evaluable patients with r/r follicular lymphoma (FL) who received doses 0.8-2.0 mg/kg, the ORR was 41.2% (7/17), including 23.5% (4/17) CR. The median progression free survival (PFS) assessed by investigator was 10.58 months with median follow-up of 11.53 months. The 9-month, 12-month, and 18-month PFS was 53.8%, 44.9% and 44.9%, respectively. The median duration of response (DoR) was not reached and the 26-week DoR rate among the 7 patients with objective response was 100%. No DLT was observed. The most frequent treatment related adverse events (TRAEs) (≥20%) were WBC decreased (66.7%), anemia (64.6%), lymphocyte decreased (60.4%), ANC decreased (47.9%), PLT decreased (47.9%) and infusion-related reactions (35.4%). Grade ≥ 3 TRAEs occurred in 33 (68.8%) patients, with the most common (≥10%) being lymphocyte decreased (58.3%), WBC decreased (20.8%), ANC decreased (18.8%) and anemia (10.4%). Six (12.5%) patients experienced treatment related serious adverse event. Discontinuation due to AEs occurred in 1 patient (grade 4 PLT decreased without bleeding occurred after DLT evaluation period). No AE led to death. IMM0306 exhibited non-linear PK characteristics across the dose range of 0.04 to 2.0 mg/kg and no apparent accumulation was observed after repeated dosing. Forty-six patients were included in the ADA analysis set, and only 2 (4.3%) patients were ADA positive after IMM0306 administration. No significant effects of ADA on PK, safety and efficacy were observed. At 1.2 mg/kg, CD47 receptor occupancy on peripheral lymphocytes was saturated, suggesting IMM0306 is well tolerated from perspective of CD47 engagement in high dose cohorts (1.2-2.0 mg/kg). B-cell counts depleted rapidly at doses 0.8-2.0 mg/kg. Elevated cytokines levels were observed after first dosing of IMM0306, but multiple dosing did not stimulate further cytokine activation. The RP2D was determined as 2.0 mg/kg based on the integrated evidence from safety, efficacy, PK and PD.
Conclusions: IMM0306 demonstrated a manageable safety profile and a favorable anti-tumor activity for patients with r/r CD20-positive B-NHL, especially in patients with r/r FL.
Disclosures: No relevant conflicts of interest to declare.