P1, N=0, Withdrawn, Masonic Cancer Center, University of Minnesota | N=34 --> 0

P1, N=33, Suspended, Masonic Cancer Center, University of Minnesota | Recruiting --> Suspended

P1, N=11, Active, not recruiting, Masonic Cancer Center, University of Minnesota | Trial primary completion date: Dec 2025 --> Jan 2024

P1, N=11, Active, not recruiting, Masonic Cancer Center, University of Minnesota | Recruiting --> Active, not recruiting | N=50 --> 11

We hypothesized that the addition of Dara to fludarabine and cyclophosphamide would enhance lymphodepletion and augment ADCC for CD38+ AML leading to better response rates when combined with FT538. FT538 in combination with daratumumab has been tolerated in a highly pre-treated cohort of patients with expected toxicities and a signal of efficacy.

iPSC-derived NK therapy offers a standardized, off-the-shelf option for NK cell therapies. FT538 iPSC-derived NK cells induce apoptosis in AML cell lines and patient samples in a dose-dependent manner and show a synergistic effect with Venetoclax, Gilteritinib, Azacitidine, and Cytarabine. Therefore, iPSC-derived NK cell therapy may be a promising possibility for AML treatment, particularly for patients resistant to standard therapies.

Pts had received a median of 2.0 (1.0 –10.0) prior lines of treatment with 13 pts (30.2%) reporting prior hematopoietic stem cell transplantation and 36 pts (83.7%) with prior exposure to venetoclax. SAR'579 was well tolerated up to doses of 6000 µg/kg QW with observed clinical benefit in pts with R/R AML. The results are consistent with the predicted favorable safety profile.

P1, N=72, Terminated, Fate Therapeutics | Trial completion date: May 2039 --> Oct 2023 | Active, not recruiting --> Terminated | Trial primary completion date: May 2024 --> Oct 2023; The study was terminated by the Sponsor.

P1/2, N=126, Recruiting, Sanofi | N=82 --> 126

P1, N=16, Terminated, Fate Therapeutics | Trial completion date: Aug 2025 --> Aug 2023 | Active, not recruiting --> Terminated; This study was terminated by the Sponsor.

Observed peak cytokine levels did not show significant dose-related increase and no association between elevated peak cytokine levels and clinical responses. The results are consistent with the improved safety profile compared to CD123-targeted T-cell engagers.

P1, N=72, Active, not recruiting, Fate Therapeutics | Recruiting --> Active, not recruiting | N=234 --> 72

P1, N=16, Active, not recruiting, Fate Therapeutics | Recruiting --> Active, not recruiting | N=189 --> 16

In Regimen B, conditioning chemotherapy (fludarabine 30 mg/m2 and cyclophosphamide 300 mg/m2) followed by 3 once-weekly doses of FT538 (Days 1, 8, 15 of a 28-d cycle), ranging from 100 million cells/dose up to 1.5 billion cells/dose, are being evaluated using a standard 3 + 3 dose-escalation design. Administration of up to 3 doses of FT538 cells at 100 or 300 million cells/dose in combination with daratumumab is safe and well tolerated without CRS, neurotoxicity, or GvHD. Interim clinical data, including safety and tolerability and initial anti-tumor activity from the ongoing Phase I dose-escalation study of FT538 in combination with daratumumab in R/R MM, will be presented at the conference.

B7-H3 TriKE may be particularly useful for patients with bone lesions or as consolidative therapy. Commercial manufacturing of B7-H3 TriKE (GTB-5550) has begun, and a phase I trial is expected in late 2023.

Anti-CD38 therapeutic monoclonal antibodies (mAbs) such as daratumumab (dara) have shown wide application and therapeutic benefit for Multiple Myeloma (MM) patients...To evaluate the effect of anti-CD38 mAb on host lymphocyte reconstitution we used flow cytometry to characterize PBMCs or marrow collected from MM patients after LDC with cytoxan 300 mg/m2 and fludarabine 30 mg/m2 x 3 days either as monotherapy (N = 4) or in combination with dara 16 mg/kg 1 week prior to LDC (Day -11) and weekly thereafter (n = 3) (NCT05182073)...In the presence of anti-CD38 mAb treatment, B2M/CIITA-null FT538 continued to persist while allogeneic NK cells were not detected, while in the study arm that lacked anti-CD38 mAb, B2M/CIITA-null FT538 was eliminated by the persisting allogeneic NK cells (p<0.001). In summary, these data demonstrate the potential to combine off-the-shelf iPSC-derived CD38-null NK cells with anti-CD38 mAb as a novel therapeutic strategy, uniquely demonstrating the potentiating of ADCC while reducing or eliminating the need for LDC in cell therapy.

As proof of concept, a clinical trial of GTB-3550 (a CD33-targeted Tri-specific Killer Engager [TriKE] in AML) induced endogenous NK cell expansion and activation in refractory AML patients. Here we developed GTB-5550 (a B7H3 TriKE) as a novel dual camelid (cam) TriKE containing WT IL-15 and comprised of two cam engagers: targeting CD16 on NK cells and B7H3 on multiple solid tumors...Conclusions B7H3 TriKE delivers an NK cell specific IL-15 signal to expand NK cells and is highly specific against a broad array of cancers. Clinical manufacturing is underway with an IND planned to open clinical trials in 2023 in a number of solid tumors and multiple myeloma.