First Patient Dosed in Phase 1/1b Trial of PRGN-3007 CAR-T Cell Therapy in Solid Tumors, Hematologic Malignancies

Javier Pinilla-Ibarz, MD, PhD

The first patient has been dosed in the phase 1/1b dose-escalation and -expansion study (NCT05694364) of PRGN-3007, Precigen’s investigational and first-in-class multigenic, autologous CAR-T cell therapy, according to a company announcement.¹

The trial is seeking to enroll 88 participants with solid tumors—including those with breast adenocarcinomas encompassing triple negative breast cancer—and patients with chronic lymphocytic leukemia (CLL), mantle cell lymphoma, acute lymphoblastic leukemia, and diffuse large B-cell lymphoma.² According to GlobalData’s epidemiology market size research,^3-8 the estimated patient population for these target areas is upward of 100,000 in the United States, European Union, and Japan.

"We are excited to work with Precigen and announce that the first patient, a CLL patient, has been dosed in the first-in-human study of PRGN-3007 UltraCAR-T," principal investigator Javier Pinilla-Ibarz, MD, PhD, a senior member, Lymphoma Section Head, and director of Immunotherapy in the Malignant Hematology Department at H. Lee Moffitt Cancer Center and Research Institute, said in a statement.¹ "ROR1 is a promising target for addressing a wide variety of tumors and we are hopeful that the PRGN-3007 study will further the development of this novel CAR-T treatment, which combines intrinsic PD-1 inhibition and ease of administration from the validated overnight manufacturing of UltraCAR-T performed at our medical center bringing therapy to patients within one day."

The phase 1/1b clinical trial has an open-label design and is enrolling in 2 parts: an initial 3+3 dose escalation in each arm followed by a dose expansion at the maximum tolerated dose (MTD). The dose levels being explored are 1x10⁶ cells/kg (Level 1), 3x10⁶ cells/kg (Level 2), and 1x10⁷ cells/kg (Level 3). Arms 1 and 2 will be enrolled in parallel, with the study grouping participants into Group A—those with hematologic malignancies—and Group B—those with solid tumors.

READ MORE: First Patient With HPV16+ Solid Tumors in SQZ-AAC-HPV Trial Achieves CR

Prior to infusion of PRGN-3007, those in Group A will undergo leukapheresis followed by lymphodepletion, the latter of which will include 3 days of fludarabine 30 mg/m² and cyclophosphamide 500 mg/m² prior to study day 0. Those in Group B will also undertake leukapheresis followed by lymphodepletion prior to PRGN-3007 infusion, though in this group, lymphodepletion will only include 2 days of cyclophosphamide 500 mg/m² prior to study day 0.

"Dosing the first patient with PRGN-3007, the next generation of UltraCAR-T incorporating PD-1 inhibition, is a significant milestone for the UltraCAR-T platform," Helen Sabzevari, PhD, president and CEO of Precigen, said in a statement.¹ "The PRGN-3007 study targets a broad range of hematological and solid tumor indications and this milestone helps us move closer to our vision for UltraCAR-T, which aims to deliver a library of personalized autologous UltraCAR-T therapies using overnight manufacturing at the patient's medical center."

PRGN-3007 is an UltraCAR-T therapy that uses Precigen's nonviral gene delivery system and overnight, decentralized manufacturing process. The treatment is engineered using a single multicistronic transposon plasmid to express a CAR targeting ROR1, membrane-bound interleukin–15 (mbIL15), a kill switch, and a novel mechanism for the intrinsic blockade of PD-1 gene expression. PRGN-3007’s design, according to Precigen, seeks to eliminate the need for combination treatment by avoid systemic toxicity and the high cost of checkpoint inhibitors.¹

Late last year, at the 64th American Society of Hematology (ASH) Annual Meeting, held December 10-12, 2022, in New Orleans, Louisiana, Precigen presented the phase 1/1b study design, noting that the trial was open for enrollment.⁹

In 2021, the FDA cleared the company’s investigational new drug (IND) application for the trial.¹⁰ At the time of the IND acceptance, Hatem Soliman, MD, medical director of the Clinical Trials Office at H. Lee Moffitt Cancer Center & Research Institute, and the principal investigator for the triple negative breast cancer cohort, said that, "ROR1 expression is thought to be a potential adverse prognostic factor in [patients with triple negative breast cancer]. Given the aggressive nature of [triple negative breast cancer] and the need for additional treatment options, we are eager to investigate PRGN-3007 in this setting."¹⁰

REFERENCES
1. Precigen Announces Further Advancement of UltraCAR-T® Platform with First Patient Dosed in Phase 1/1b Dose Escalation/Dose Expansion Study of PRGN-3007 in Advanced ROR1+ Hematological and Solid Tumors. News release. Precigen inc. March 29, 2023. Accessed March 30, 2023. https://prnmedia.prnewswire.com/news-releases/precigen-announces-further-advancement-of-ultracar-t-platform-with-first-patient-dosed-in-phase-11b-dose-escalationdose-expansion-study-of-prgn-3007-in-advanced-ror1-hematological-and-solid-tumors-301784205.html
2. Dose Escalation/Dose Expansion Study of PRGN-3007 UltraCAR-T Cells in Patients With Advanced Hematologic and Solid Tumor Malignancies. US National Library of Medicine. Clinicaltrials.gov. Last updated January 23, 2023. Accessed March 30, 2023. https://clinicaltrials.gov/ct2/show/NCT05694364
3. Likelihood of Approval and Phase Transition Success Rate Model – PRGN-3007 in Triple-Negative Breast Cancer (TNBC). GlobalData. February 18, 2023. Accessed March 30, 2023. https://www.globaldata.com/store/report/prgn-3007-in-triple-negative-breast-cancer-tnbc-loa-and-ptsr-drug-analysis-392875/
4. Likelihood of Approval and Phase Transition Success Rate Model – PRGN-3007 in Mantle Cell Lymphoma. GlobalData. February 18, 2023. Accessed March 30, 2023. https://www.globaldata.com/store/report/prgn-3007-in-mantle-cell-lymphoma-loa-and-ptsr-drug-analysis-392875/
5. Likelihood of Approval and Phase Transition Success Rate Model – PRGN-3007 in Solid Tumor. GlobalData. February 18, 2023. Accessed March 30, 2023. https://www.globaldata.com/store/report/prgn-3007-in-solid-tumor-loa-and-ptsr-drug-analysis-392875/
6. Likelihood of Approval and Phase Transition Success Rate Model – PRGN-3007 in Diffuse Large B-Cell Lymphoma. GlobalData. February 18, 2023. Accessed March 30, 2023. https://www.globaldata.com/store/report/prgn-3007-in-diffuse-large-b-cell-lymphoma-loa-and-ptsr-drug-analysis-392875/
7. Likelihood of Approval and Phase Transition Success Rate Model – PRGN-3007 in Relapsed Chronic Lymphocytic Leukemia (CLL). GlobalData. February 18, 2023. Accessed March 30, 2023. https://www.globaldata.com/store/report/prgn-3007-in-relapsed-chronic-lymphocytic-leukemia-cll-loa-and-ptsr-drug-analysis-392875/
8. Likelihood of Approval and Phase Transition Success Rate Model – PRGN-3007 in Refractory Chronic Lymphocytic Leukemia (CLL). GlobalData. February 18, 2023. Accessed March 30, 2023. https://www.globaldata.com/store/report/prgn-3007-in-refractory-chronic-lymphocytic-leukemia-cll-loa-and-ptsr-drug-analysis-392875/
9. Ibarz JP, Lankford A, Sabzevari H, et al. A Phase1/1b Dose Escalation/Dose Expansion Study of Prgn-3007 Ultracar-T Cells in Patients with Advanced Hematologic and Solid Tumor Malignancies. Presented at: ASH 2023; December 11, 2022; New Orleans, LA + Virtual. Poster 3334