890MO - Phase I Alexander study of AUTO3, the first CD19/22 dual targeting CAR.T cell, with pembrolizumab in patients with relapsed/refractory (r/r) DLBCL

Background

CD19 directed CAR T cells are effective in patients with r/r DLBCL, however relapses due to CD19 loss or PDL1 upregulation are common. In this study, we evaluate the safety and efficacy of AUTO3, a CAR T targeting CD19/22 with limited duration of PD-1 blockade.

Methods

We constructed a bicistronic retroviral vector encoding both an anti-CD19 (OX40 co-stim) and an anti-CD22 (41BB co-stim) CAR with humanized binders. The cell product was manufactured in a semi-automated and closed process using CliniMACS Prodigy. Patients (≥ 18 years) with r/r DLBCL (NOS) or transformed (tDLBCL); ECOG < 2, adequate organ function are eligible. Lymphodepletion was Flu/Cy prior to AUTO3. Bridging therapy was allowed. The three dose levels explored are 50, 150, and 450 x 10⁶ CAR T-cells. Patients received AUTO3 alone, or with 3 doses of pembrolizumab (pem) 200 mg q 3 wks starting on D14 (regimen A), or with a single dose of pem 200 mg on D-1 (regimen B). The primary endpoint is frequency of DLTs and grade (G) 3-5 adverse events (AE) and secondary endpoints included ORR, CRR, and biomarkers.

Results

As of April 27, 2020, 23 patients were treated with AUTO3 in the ongoing phase I study. The median age was 57 (28 - 83) and median number of prior therapies was 3 (2 - 10). 87% had refractory disease, 74% were DLBCL NOS, and 26% were tDLBCL. Dose escalation from 50 to 450 x 10⁶ cells with pem regimen A and B have been completed without DLTs. G ≥ 3 treatment emergent AEs that occurred ≥ 25% were neutropenia (87%), thrombocytopenia (57%), and anemia (48%). Majority of Serious AE were hematological related and reversible. There were 0 cases of severe cytokine release syndrome (sCRS) or neurotoxicity (NT) of any grade at > 50 x 10⁶ cells. Among the 16 patients treated at dose > 50 x 10⁶, the ORR was 69% and CRR was 56%, and all CRs are ongoing at a median f/u 3 months (1-12 months). Among the 8 patients treated at a dose > 50 x 10⁶ with D-1 pem, the ORR was 75% and CRR was 63%. Additional data from patients treated at the recommended phase II dose as well as patients treated in an out-patient setting and longer follow up, as well as relevant biomarkers will be presented.

Conclusions

AUTO3 at > 50 x 10⁶ CAR T cells with pembrolizumab induces CRs without severe CRS or NT of any grade.

Clinical trial identification

EudraCT Number: 2016-004682-11.

Editorial acknowledgement

Legal entity responsible for the study

Autolus Therapeutics.

Funding

Autolus Therapeutics.

Disclosure

E. Tholouli: Advisory/Consultancy: Astellas; Advisory/Consultancy: Celgene; Advisory/Consultancy: Daiichi-Sankyo; Advisory/Consultancy: Kite; Advisory/Consultancy: Janssen; Advisory/Consultancy: Jazz; Advisory/Consultancy: Kiadis; Advisory/Consultancy: Novartis; Advisory/Consultancy: Pfizer. W. OSBORNE: Advisory/Consultancy: Autolus Therapeutics; Advisory/Consultancy: Roche; Advisory/Consultancy: Takeda; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Servier; Advisory/Consultancy: Kite; Advisory/Consultancy: MSD; Advisory/Consultancy: Novartis; Advisory/Consultancy: Beigene. A. Ramakrishnan: Advisory/Consultancy: Takeda; Advisory/Consultancy: Amgen; Honoraria (self): Cigna. Y. Zhang: Full/Part-time employment: Autolus Therapeutics. S. Thomas, M. Al-Hajj, M. Pule, M. Jonnaert, V. Peddareddigari, N. Khokhar, R. Chen: Full/Part-time employment: Autolus Therapeutics. All other authors have declared no conflicts of interest.