Golidocitinib Induces Responses With Manageable Safety in R/R PTCL

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Among patients with refractory/relapsed (R/R) peripheral T-cell lymphoma (PTCL) treated with golidocitinib, antitumor responses and tumor shrinkage were observed across all subtypes with reversible or manageable adverse events (AEs), according to findings from the phase 2 JACKPOT8 study (NCT04105010).

Findings presented during the 2023 American Society of Hematology Annual Meeting and Exposition showed that of the 88 patients who were response-evaluable and treated with golidocitinib, the objective response rate (ORR) per independent review committee (IRC) was 44.3%. This included a complete response (CR) rate of 23.9% and a partial response (PR) rate of 20.5%. Stable disease was observed in 19.3% of patients, progressive disease was seen in 22.7%) and 13.6% were not evaluable.

The multinational JACKPOT8 trial included patients with locally diagnosed R/R PTCL who were 18 years or older (or at least 19 years of age if they were Korean), with measurable disease, an ECOG performance status of 2 or less, and adequate organ function. Golidocitinib was given to patients at a dose of 150 mg daily in 21-day cycles and later determined to be the recommended phase 2 dose of the study. The primary end point was ORR per IRC, and secondary end points consisted of CR rate, duration of response (DOR), progression-free survival (PFS), time to response, and safety.

Further, the median DOR was 20.7 months (95% CI, 17.6-not evaluable [NE]) per IRC assessment, and 53.8% of patients still were responding at the data cutoff date of August 31, 2023. The median PFS and median overall survival rates were 5.6 months and 19.4 months, and 52.3% of patients alive at the data cutoff. Additionally, those who had a CR or PR had a median DOR of 20.7 months (95% CI, 17.6-NE) and 3.9 months (95% CI, 2.1-NE), respectively.

For safety, the majority of patients (92.3%) had a treatment-related AE (TRAE) of any grade, while 59.6% of patients reported having a grade 3 or higher TRAE, and 24.0% had a treatment-related serious AE. TRAEs of any-grade were mostly hematological, including thrombocytopenia (62.5%), leukopenia (57.7%), neutropenia (56.7%), anemia (41.3%), lymphocytopenia (30.8%), increased aspartate aminotransferase (28.8%), increased alanine aminotransferase (25.0%), and increased blood creatine (18.3%).These were also notably reversible or clinically manageable.

In an interview with Targeted Oncology^TM, Yuqin Song, MD, PhD, an oncologist at the Peking University Cancer Hospital and Institute in Beijing, China, discussed golidocitinib as the first JAK1 inhibitor developed for patients with T-cell lymphomas in this pivotal study.

Targeted Oncology: What is the significance of the JACKPOT8 study in the context of treating R/R PTCL?

Song: Peripheral T-cell lymphoma is a relative group of lymphoid malignancies in China and also in Asian countries. But for the patients, we have a rare standard treatment for this group of patients, especially for relapsed or refractory peripheral T-cell lymphoma. This agent may be the only JAK1 selective inhibitor entering a pivotal phase 2 study in peripheral T-cell lymphoma, so it is important. In the final analysis of this study, it showed a high efficacy and safety profile, so it may give more choices to our patients.

What were the key findings from the study?

JACKPOT8 started with part A. It was a dose-escalation and dose-expansion study. We confirmed the recommended phase 2 dose as 150 mg twice daily for the phase 2 study. In this phase 2 study, part B of the JACKPOT8, we enrolled 104 patients. For this group of patients, that overall response rate was [44.3%,] and the [complete response] rate was also 24%.The data was satisfactory. We are looking forward to the final approval for marketing, even in other countries.

What are some of the most common adverse events associated with this treatment?

Just like other novel agents in lymphoid malignancies, hematological

adverse events were the most common adverse events, such as cytopenia, thrombocytopenia, neutropenia, and lymphopenia. For patients [with toxicities], treatment should be reduced or interrupted. For those patients with hematological events, they should be given some supportive care.

Are there any other ongoing or planned studies investigating this agent in this space?

At the present time, other countries are participating, and they have started, especially the United States and Australia. In this phase 2 study, we have 5 patients from Australia and the United States, and we have more countries to participate in this study. The final data was published online in Lancet Oncology. We are looking forward to the approval for marketing in China, but as a single-arm study, approval for marketing is relatively difficult. We hope to get approval based on this single-arm study, but we note that we may try to do a phase 3 study to compare this agent to other agents in this group of patients. We are also looking forward to the future. We hope to move this agent to be a first-line choice, adding to the standard treatments. such as CHOP [cyclophosphamide, doxorubicin, vincristine, and prednisone] and CHOEP [etoposide, vincristine, doxorubicin, cyclophosphamide, and prednisone] regimens.

What are your hopes for the future of the peripheral T-cell lymphomas space?

Concurrently, we just finished comparing all 3 trials of novel agents in relapsed or refractory peripheral T-cell lymphomas. We hope all those agents can be approved based on a phase 3, single-arm study so we can provide more choices for our patients.

REFERENCE:

Song Y, Malpica L, Cai Q, et al. Golidocitinib in treating refractory or relapsed peripheral T- cell lymphoma: full analysis of the multinational pivotal study results (JACKPOT8). Blood. 2023;142(suppl1):305. doi:10.1182/blood-2023-172962