briquilimab (JSP191)

P1/2, N=18, Recruiting, Jasper Therapeutics, Inc.

P1/2, N=72, Recruiting, National Heart, Lung, and Blood Institute (NHLBI) | Not yet recruiting --> Recruiting

P1/2, N=44, Recruiting, Jasper Therapeutics, Inc.

P2, N=32, Recruiting, National Cancer Institute (NCI) | Not yet recruiting --> Recruiting

GVHD prophylaxis was tacrolimus, sirolimus, and mycophenolate mofetil. These results demonstrate that targeting CD117 with briquilimab together with TBI/Flu as a novel conditioning regimen is safe, well-tolerated, facilitates full donor myeloid chimerism, and sustained clearance of MRD in older adults with AML in CR and MDS without TP53 undergoing NMA AHCT.

Objective: To reduce acute and long-term treatment-related toxicities, we have developed a first of its kind treatment intended to improve the safety of allo-HSCT through: 1) a TBI- and busulfan-free conditioning regimen consisting of briquilimab, rabbit ATG (rATG - Thymoglobulin), fludarabine, cyclophosphamide and rituximab - briquilimab (formerly called JSP191) is a monoclonal antibody (mAb) that targets human CD117 to deplete host HSCs enabling blood and immune reconstitution with minimal toxicity with the other agents being used for transient immune suppression to prevent immunologic rejection; 2) transplantation of TCRαβ+ T-cell/CD19+ B-cell hematopoietic grafts - a stem cell therapy that enhances donor hematopoietic and immune reconstitution while decreasing GvHD; and 3) a pre- and post-transplant monitoring protocol to maximize engraftment. All three patients in the Phase 1b portion of the study show early safety and efficacy of this approach. Briquilimab was well tolerated and all patients have shown prompt and durable donor engraftment. This data indicates that it might be possible to remove irradiation or alkylator chemotherapy from the conditioning regimen in patients with FA without matched sibling donors thus decreasing the chances for cancer predisposition in these patients that have inherited DNA repair defects.

Recent prospective data from the phase III ASAP Trial also suggest that in patients with poor response after initial first induction therapy or relapsed AML watchful waiting and sequential conditioning prior to allogeneic HCT result in comparable CR rates as could be observed with salvage chemotherapy with high-dose cytarabine plus anthracycline...Early HLA-typing of AML patients and their family members (possibly at the time of diagnosis), conditioning regimens incorporating novel agents, such as briquilimab or 131I-apamistamab, engineered donor grafts and maintenance therapy with novel agents or cell therapeutics have the potential to improve disease-free and overall survival in this patient population through improved disease control...Allogeneic HCT should be considered in this patient population, preferably in the context of a clinical trial testing novel treatment modalities. Updated prognostic score systems have the potential to identify subgroups of patients deriving the most benefit from these approaches.

P2, N=32, Not yet recruiting, National Cancer Institute (NCI)

P1, N=30, Recruiting, Jasper Therapeutics, Inc.

GVHD prophylaxis was tacrolimus, sirolimus, and mycophenolate mofetil (MMF), which when given with Flu/TBI has previously resulted in grade 2-4 acute GVHD (aGVHD) of 26% by transplant day (TD)+100 and chronic GVHD (cGVHD) of 49% (Sandmaier et al, 2019). To date, cumulative incidences of gr2-4 aGVHD and cGHVD are 13.8% and 34.5%, respectively. Addition of briquilimab to Flu/TBI does not appear to increase GVHD ​compared to previously published rates. Increased levels of IL-6 in subjects with aGVHD and decreased number of Treg population in subjects with cGVHD suggest their utility as diagnostic biomarkers for GVHD.

GVHD prophylaxis was tacrolimus, sirolimus, and mycophenolate mofetil. These early results demonstrate that outpatient HCT is clinically feasible and may be associated with lower hospital resource use, while sparing hospitals and patients a lengthy hospitalization. We believe that outpatient HCT enabled by safe, targeted antibody-based conditioning can serve as a strategy to increase hospital bed availability and reduce the $250,000 or more that is spent per patient on HCT in the US, today (Broder et al., 2017; Murthy et al., 2019). JSP191 will be studied in a phase 3 randomized trial for older AML and MDS patients, beginning enrollment in 2023.

GVHD prophylaxis was tacrolimus, sirolimus, and mycophenolate mofetil (MMF), which when given with Flu/TBI has previously resulted in grade (gr) 2-4 acute GVHD (aGVHD) of 26% by transplant day (TD)+100 and chronic GVHD (cGVHD) of 49% (Sandmaier et al, 2019). To date, cumulative incidence of gr 2-4 aGVHD and cGHVD is 13.8% and 27.6%, respectively. In 20 subjects with >TD+180 follow up, cGVHD incidence is 40%. Addition of JSP191 to Flu/TBI does not appear to increase GVHD compared to previously published rates.

GVHD prophylaxis was tacrolimus, sirolimus, and mycophenolate mofetil. These results demonstrate that targeting CD117 with JSP191 together with TBI/Flu as a novel conditioning regimen is safe, well-tolerated, can facilitate full donor myeloid chimerism, and can result in clearance of AML MRD in older AML in CR patients undergoing NMA HCT.

Model predictions were within 1.5-fold of observed values for 7E3 plus IVIG and tesidolumab plus IVIG as well as for JSP191 administered alone. Based on our simulations, IVIG doses ≥ 500 mg exceeded the 80-125 percent no-effect boundaries. IVIG treatment with monoclonal antibodies in patients with PI may result in a clinically significant interaction, depending on the IVIG dose administered and the exposure response relationship for the specific monoclonal antibody.

GVHD prophylaxis was tacrolimus, sirolimus, and mycophenolate mofetil. These early results demonstrate that targeting CD117 with JSP191 together with TBI/Flu as a novel conditioning regimen is safe, well-tolerated, facilitates full donor myeloid chimerism, and clearing MDS/AML MRD in older adults undergoing NMA AHCT. .

We reasoned that adding JSP191 to a standard NMA conditioning of 2 Gy TBI and fludarabine (Flu) would be safe and result in depletion of measurable residual disease (MRD) in older adults with high-risk MDS/AML entering AHCT...GVHD prophylaxis was tacrolimus, sirolimus, and mycophenolate mofetil... These early results are the first to demonstrate that JSP191/TBI/Flu is safe, well-tolerated, and capable of clearing MDS/AML MRD in older adults undergoing NMA AHCT.

GVHD prophylaxis included tacrolimus, sirolimus, and mycophenolate mofetil... These early results are the first to demonstrate that JSP191/TBI/Flu is safe, well-tolerated, and capable of clearing MDS/AML MRD in older adults undergoing NMA AHCT. Accrual onto this study is continuing. Correlative analyses demonstrating the impact of JSP191 on HSCs are ongoing and will be presented at the meeting.

GVHD prophylaxis included tacrolimus, sirolimus, and mycophenolate mofetil... These early results are the first to demonstrate that JSP191/TBI/Flu is safe, well-tolerated, and capable of clearing MDS/AML MRD in older adults undergoing NMA AHCT. Accrual onto this study is continuing. Correlative analyses demonstrating the impact of JSP191 on HSCs are ongoing and will be presented at the meeting.

GVHD prophylaxis included tacrolimus, sirolimus, and mycophenolate mofetil... These early results are the first to demonstrate that JSP191/TBI/Flu is safe, well-tolerated, and capable of clearing MDS/AML MRD in older adults undergoing NMA AHCT. Accrual onto this study is continuing. Correlative analyses demonstrating the impact of JSP191 on HSCs are ongoing and will be presented at the meeting.

GVHD prophylaxis included tacrolimus, sirolimus, and mycophenolate mofetil... These early results are the first to demonstrate that JSP191/TBI/Flu is safe, well-tolerated, and capable of clearing MDS/AML MRD in older adults undergoing NMA AHCT. Accrual onto this study is continuing. Correlative analyses demonstrating the impact of JSP191 on HSCs are ongoing and will be presented at the meeting.

GVHD prophylaxis included tacrolimus, sirolimus, and mycophenolate mofetil... These early results are the first to demonstrate that JSP191/TBI/Flu is safe, well-tolerated, and capable of clearing MDS/AML MRD in older adults undergoing NMA AHCT. Accrual onto this study is continuing. Correlative analyses demonstrating the impact of JSP191 on HSCs are ongoing and will be presented at the meeting.