Combining a CDK9 inhibitor with venetoclax and prednisone led to encouraging responses in patients with lymphoid malignancies in the dose-escalation arm of a phase 1 clinical trial.
Enitociclib (VIP152), a highly selective CDK9 inhibitor, plus venetoclax (Venclexta) and prednisone displayed promising clinical results when used for the treatment of relapsed/refractory (R/R) lymphoma, according to findings from the dose-escalation arm of a phase 1 study (NCT05371054).1
Investigators from the National Institute of Health-sponsored study reported 2 partial responses (PRs) in 3 patients with peripheral T-cell lymphoma (PTCL), as well as 1 PR in 2 patients with double-hit diffuse large B-cell lymphoma (DH-DLBCL).
Further, a patient with angioimmunoblastic T-cell lymphoma experienced a PR with a 91% reduction in tumor burden at the first dose level; the patient remains on the study for follow-up. Another patient with PTCL experienced a PR with an 86% reduction in pulmonary lesions and a complete resolution of skin lesions at the second dose level. A patient with DH-DLBCL achieved a PR after 1 treatment cycle. So far, no dose-limiting toxicities have been observed.
“Enitociclib continues to differentiate itself in the CDK9 inhibitor field,” said Ahmed Hamdy, MD, chief executive officer of Vincerx, in a press release. “Enitociclib is well tolerated, making it ‘the partner of choice’ for novel combinations. We are pleased to see the high response rate and tolerability of enitociclib in combination with venetoclax and prednisone in patients with hard-to-treat types of non-Hodgkin lymphoma such as [PTCL] and [DH-DLBCL]. Previous reports of venetoclax monotherapy in PTCL show low response rates; thus, we believe we are seeing compelling evidence for synergism between enitociclib and venetoclax in this patient population.”
The dose-escalation study has an estimated enrollment of 130 patients with R/R lymphoid malignancies. The primary end points are complete response rate and incidence of adverse events. The secondary end points are progression-free survival, time to response, duration of response, overall response rate, overall survival, and event-free survival.2
Patients in the dose-escalation phase are receiving enitociclib and venetoclax at escalating doses with prednisone at fixed doses to identify the maximum tolerated dose and recommended phase 2 dose (RP2D). In the dose-expansion phase, patients will receive enitociclib and venetoclax at the RP2D and prednisone at fixed doses.
To be eligible for participation, patients must have 1 of the following histologically or cytologically confirmed lymphoid malignancies:
Patients must also have an ECOG performance status of 2 or lower, have adequate organ and marrow function, use adequate contraception, and discontinue breastfeeding through 90 days after the last administration of the study drug, if applicable, to be included in the study. Patients cannot have received any anti-cancer treatment within 2 weeks, radio- or toxin-immunoconjugates within 10 weeks, or a prior allogeneic stem cell transplant within 6 months of the first dose of the study drug.
The study has an estimated primary completion date of March 11, 2024.