800MO - First report of BCL-2 inhibitor TQB3909 in pts with relapsed or refractory non-Hodgkin lymphoma (NHL) and acute myeloid leukemia (AML): Data from a phase I study

Background

TQB3909 is a novel, highly selective BCL-2 inhibitor that has shown the potential to induce deeper responses. Here we report a first-in-human study of TQB3909 in pts with R/R NHL and AML.

Methods

TQB3909-I-01 (NCT04975204) is a phase 1 study including dose escalation and expansion phases. The primary objectives were to evaluate safety and efficacy and determine MTD and RP2D. NHL pts received escalating doses of TQB3909 (100-1200mg QD) with a daily ramp-up from 20mg. AML pts received TQB3909 (200-800mg QD) with a daily ramp-up from 100mg. 3+3 was performed to evaluate DLTs for 2 cohorts separately. AEs were reported per NCI CTCAE v5.0.

Results

As of April 24, 2024, 69 pts were treated. 52 NHL (18 CLL/SLL, 34 NHL) received TQB3909 including 100mg (n=6), 200mg (n=9), 400mg (n=26), 600mg (n=5), 800mg (n=3) and 1200mg (n=3). 17 AML received TQB3909 including 200mg (n=4), 400mg (n=7), 600mg (n=3) and 800mg (n=3). The median age was 61 years (range 23-80). The median lines of prior treatment were 2 for NHL and 1 for AML, respectively. As of January 31, 2024, with a median treatment duration 3.7 months (range 0.1-22.9), no DLTs occurred and MTD has not been reached. 95.6% and 60.3% reported at least 1 TRAEs and grade ≥3 TRAEs. The most common hematological TRAEs (grade ≥3) were leukopenia (70.6%; 30.9%), neutropenia (61.8%; 38.2%), anemia (45.6%; 14.7%), thrombocytopenia (44.1%; 19.1%) and lymphocytopenia (33.8%; 13.2%). The most common non-hematological TRAEs were diarrhea (55.9%), hyperuricaemia (42.6%) and hyperbilirubinaemia (36.8%), mostly grade 1-2. 8.8% reported treatment related SAEs and 4.4% discontinued TQB3909 due to TEAEs. 5 pts (7.4%) reported laboratory TLS. No clinical TLS and treatment related death were reported. As of April 24, 2024, 88.9% (16/18) CLL/SLL achieved responses, 8 CR/CRi and 8 PR. With a median follow up 9.5 months, mDOR and mPFS were not reached. 37.5% (12/32) B-NHL achieved responses. Of 16 evaluable AML, 1 (6.3%) achieved CR and 4 (25.0%) achieved CRi.

Conclusions

TQB3909 demonstrated significant efficacy in pts with R/R B-NHL with manageable safety profiles, providing a promising treatment option for B-NHL pts including CLL/SLL pts who were refractory to BTK inhibitors.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

CTTQ - Chia Tai Tianqing Pharmaceutical Group Co., Ltd.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.