Phase 1 Trial of SC-DARIC33 in Pediatric R/R Acute Myeloid Leukemia Pauses

In the open-label, non-randomized phase 1 PLAT-08 trial study, investigators are assessing the feasibility and safety of SC-DARIC33 among pediatric and young adult patients with relapsed/refractory, CD33-positive leukemia with or without prior receipt of allogeneic hematopoietic stem cell transplantation.

The Seattle Children’s Hospital has paused the investigation of SC-DARIC33 among pediatric patients with relapsed/refractory acute myeloid leukemia (AML) in the phase 1 PLAT-08 trial (NCT05105152), according to a press release from 2seventy bio, Inc.¹

The trial paused following a grade 5 serious adverse effect (SAE) that occurred in the first patient treated at the trial’s second dose level, which investigators were required by clinical study protocol to report to the FDA. Investigators are currently assessing the root cause of the SAE and any possible associations with SC-DARIC33 treatment.

“The safety of every patient who participates in our studies or is treated with our therapies is the utmost priority for us, and we are in communication with FDA while we assess the data surrounding this SAE, and the potential next steps for the study,” Steve Bernstein, MD, chief medical officer at 2seventy bio, said in the press release.

Investigators previously presented late-breaking results from the phase 1 PLAT-08 trial as part of an oral presentation at the 2023 American Society of Gene & Cell Therapy (ASGCT) Annual Meeting.² Findings highlighted the activation mechanism of SC-DARIC33 through low non-immunosuppressive concentrations of rapamycin in the blood, and that SC-DARIC33 expansion correlated with a significant transient decrease in the CD33 leukemic burden. Additionally, treatment among 3 patients receiving 1 x 10⁶ SC-DARIC33 T cells/kg was generally well tolerated and did not yield any dose-limiting toxicities as of March 17, 2023.

Another oral presentation indicated that omitting interleukin (IL)-15 from culture media boosted expansion of modified iSynPro (iSP)-IL-15 DARIC33 T cells after tumor exposure. These findings suggested that iSP transcription may benefit T-cell function by producing IL-15 without enabling unrestrained T-cell growth.

“We are pleased to share results that demonstrate 3 key steps toward clinically meaningful outcomes: rapamycin dosing optimization, rapamycin-regulated in vivo expansion, and activation of SC-DARIC33 T cells as well as concurrent anti-CD33 activity,” Bernstein said in a press release at the time of oral presentations. “These data reinforce the potential of SC-DARIC33 as a new T-cell therapy approach in AML.”

In the open-label, non-randomized phase 1 PLAT-08 trial study, investigators are assessing the feasibility and safety of SC-DARIC33 among pediatric and young adult patients with relapsed/refractory, CD33-positive leukemia with or without prior receipt of allogeneic hematopoietic stem cell transplantation.

The primary end points of the trial include AEs related to SC-DARIC33 and the ability to manufacture SC-DARIC33. AML responses to SC-DARIC33 serves as a secondary end point.

Patients 30 years and younger with AML expressing CD33 by flow cytometry are eligible for enrollment on the trial. Additional eligibility criteria include having the ability to tolerate apheresis, a life expectancy of at least 8 weeks, an appropriate stem cell donor source, and a Lanksy performance status of at least 50 for patients younger than 16 or a Karnofsky score of at least 50 for patients 16 years and older. Patients also need to have adequate organ function and provide informed consent to enroll.

Patients with an active malignancy other than AML or a history of symptomatic non-AML central nervous system disease are unable to enroll on the trial. Patients are also unsuitable for enrollment if they have a presence of active severe infection, primary immunodeficiency syndrome, or prior virotherapy.

References

1. 2seventy bio announces clinical study pause of PLAT-08 trial of SC-DARIC33 in acute myeloid leukemia. News release. 2seventy bio, Inc. June 14, 2023. Accessed June 14, 2023. bit.ly/441rOs3
2. 2seventy bio presents late-breaking results for SC-DARIC33, an investigational CD33-targeting CAR T in pediatric and young adults with relapsed or refractory acute myeloid leukemia. News release. News release. 2seventy bio, Inc. May 19, 2023. Accessed June 14, 2023. bwnews.pr/3p0OYjH