TT11

P1/2, N=40, Recruiting, UNC Lineberger Comprehensive Cancer Center | Trial completion date: Aug 2040 --> Aug 2038 | Trial primary completion date: Aug 2025 --> Sep 2027

P1/2, N=31, Recruiting, UNC Lineberger Comprehensive Cancer Center | Not yet recruiting --> Recruiting

P2, N=20, Recruiting, UNC Lineberger Comprehensive Cancer Center

P1, N=18, Active, not recruiting, UNC Lineberger Comprehensive Cancer Center

P1/2, N=40, Recruiting, UNC Lineberger Comprehensive Cancer Center | Trial completion date: Aug 2038 --> Aug 2040 | Trial primary completion date: Aug 2023 --> Aug 2025

Two patients had cytokine release syndrome (Grade 1), which resolved without use of steroid or tocilizumab. Preliminary data demonstrated favorable safety profile and promising anti-tumor responses of CD30.CAR-T combined with nivo in r/r cHL patients after failure of frontline therapy. Evaluation of 15 patients enrolled is ongoing, and the clinical and ctDNA-MRD data will be presented at the meeting.

P1, N=21, Active, not recruiting, Tessa Therapeutics | Trial primary completion date: Mar 2023 --> Nov 2022

P1b, N=15, Active, not recruiting, Tessa Therapeutics | Recruiting --> Active, not recruiting

P1, N=60, Recruiting, Baylor College of Medicine | Trial completion date: Feb 2036 --> Feb 2040

P2, N=20, Recruiting, UNC Lineberger Comprehensive Cancer Center | Trial primary completion date: Aug 2023 --> Feb 2028

P2, N=18, Recruiting, UNC Lineberger Comprehensive Cancer Center | Not yet recruiting --> Recruiting

The recurrence of DNMT3A and PPM1D mutations indicates the selective influence of prior chemotherapeutics. Given the increasing number of patients receiving CAR-T therapy, further work must determine if high CH prevalence in this cohort is predictive of increased long-term complications in survivors.

P2, N=18, Not yet recruiting, UNC Lineberger Comprehensive Cancer Center

The efficacy and safety profile of programmed death (PD)-1 checkpoint inhibitors, nivolumab and pembrolizumab, in cHL have been well demonstrated (Chen et al., 2017; Kuruvilla et al., 2021; Younes et al., 2016), with FDA approval for r/r cHL. PD-1 checkpoint inhibitors, in combination with CD30-directed antibody therapy (brentuximab vedotin) or other chemotherapies, have also shown high efficacy in this setting (Advani et al., 2021; Mei et al., 2022; Moskowitz et al., 2021)...Following a leukapheresis procedure for manufacture of CD30.CAR-T cells, patients will be treated with 4 cycles of nivolumab every 4 weeks (Q4W), and a single infusion of CD30.CAR-T cells (given between nivolumab Cycles 2 and 3, and after lymphodepletion with bendamustine and fludarabine)...The key secondary objective is to evaluate potential anti-tumor activity, as assessed by the CR rate of autologous CD30.CAR-T in combination with nivolumab at EOT in 14 evaluable patients, as per Lugano Classification Revised Response System for malignant lymphoma (Cheson et al., 2014). Other secondary objectives are to assess the overall response rate (ORR), duration of response (DOR), and progression-free survival (PFS) of patients in the ASCT and non-ASCT groups.This study is ongoing and one patient has been enrolled to date.

The anti-PD-1 antibodies nivolumab and pembrolizumab have both been studied in phase II studies in patients with r/r cHL with ORR ranging between 65-87% and median progression free survival (PFS) ranging from 13-15 months...This study is the first to describe CD30.CAR-T expansion following anti-PD-1 therapy. While further analysis is warranted to assess for CD30.CAR-T functionality after anti-PD-1 exposure, our data suggest that anti-PD-1 therapy may rescue CD30.CAR T cells, supporting further investigations in patients with cHL.

A single infusion of CD30.CAR-T therapy rapidly induces MRD negativity in a significant subset of patients at Day 42. ctDNA as exploratory biomarker will be further evaluated in Pivotal part of the study.

Methods This is a Phase 2 single arm, multi-center study, enrolling patients (12-75 years) with cHL progression after at least 3 lines of therapy, including chemotherapy, brentuximab vedotin, and anti-programmed cell death (PD)-1 antibodies...The patients were treated with CD30.CAR-T cells, after lymphodepletion chemotherapy using bendamustine and fludarabine, with an allowable dose range of 2.0 to 2.7 × 108 CD30.CAR-T cells per m2...The CD30.CAR-T cells showed good expansion and persistence after infusion. The efficacy, safety and exploratory biomarkers of CD30.CAR-T will be further evaluated in the Pivotal segment of this Phase 2 study.

P1, N=66, Recruiting, Baylor College of Medicine | Trial primary completion date: Apr 2022 --> Apr 2026

P1, N=21, Active, not recruiting, Tessa Therapeutics | Recruiting --> Active, not recruiting

P1b, N=15, Recruiting, Tessa Therapeutics | Not yet recruiting --> Recruiting

P1b, N=15, Not yet recruiting, Tessa Therapeutics

P2, N=97, Active, not recruiting, Tessa Therapeutics | Recruiting --> Active, not recruiting | Trial completion date: Feb 2036 --> Mar 2037 | Trial primary completion date: Feb 2023 --> May 2025

P1, N=18, Active, not recruiting, UNC Lineberger Comprehensive Cancer Center | Recruiting --> Active, not recruiting

P2, N=20, Recruiting, UNC Lineberger Comprehensive Cancer Center | Trial completion date: Aug 2037 --> Aug 2038 | Trial primary completion date: Aug 2022 --> Aug 2023

To assess the safety and clinical activity of banked CD30.CAR EBVSTs, we enrolled patients with multiply relapsed (median of 4 prior lines of therapy; range 3-5) or refractory CD30-positive lymphomas in a Phase 1 dose escalation study using 4 × 10 7 , 1 × 10 8 or 4 × 10 8 CD30.CAR EBVSTs infused after cytoreduction with cyclophosphamide and fludarabine...In summary, banked CD30.CAR EBVSTs can safely be given to allogeneic recipients and may cause significant tumor responses including complete remissions. These cells may be a suitable platform for other “off-the-shelf” CAR-T cell therapies.

CD30 is a validated target for classical Hodgkin Lymphoma (cHL), as demonstrated by the activity of the anti-CD30 antibody drug conjugate, brentuximab vedotin (BV), making it an attractive target for CAR-T therapy in this disease...Eligible patients undergo leukapheresis for manufacture of CD30.CAR-T cells, followed by LD chemotherapy using bendamustine and fludarabine, prior to infusion of CD30.CAR-T with an allowable dose range of 2.0 to 2.7 × 10 8 CD30.CAR-T cells per m 2...Conclusion Preliminary data from the Pilot segment of this study confirms favorable safety profile and excellent anti-tumor responses of CD30.CAR-T in heavily-treated R/R cHL patients. The efficacy and safety of CD30.CAR-T will be further evaluated in the Pivotal segment of this Phase 2 study.

Five patients, 3 HL and 2 NHL, were enrolled on a phase Ib/II study and received 1x10 8 CD30.CAR-T cells/m 2 , as treatment for relapsed disease, after lymphodepletion with bendamustine and fludarabine (NCT02690545). HL patients had failed multiple lines of therapies (5-6), including 2 with prior pembrolizumab, 2 with prior ASCT, and all 3 with prior brentuximab vedotin (BV) and radiation therapy...The ALK negative patient had been treated with 3 prior lines of therapy and the ALK positive patient had been treated with 6 lines of prior therapy including ASCT and two ALK inhibitors, crizotinib and brigatinib...He responded to antibacterial agents and two doses of tocilizumab, as well as brief supplemental oxygen by nasal cannula... Our studies show that CD30.CAR-T cells are well tolerated in pediatric patients. CRs were observed in all heavily pre-treated and refractory HL patients, highlighting the potential of this strategy. All patients treated on both studies had previously received BV, which suggests CD30.CAR-T cells are effective even post BV progression.

To assess the safety and activity of banked CD30.CAR EBVSTs, we treated patients with multiply relapsed (median of 4 prior lines of therapy; range 3-5) or refractory CD30-positive lymphomas in a Phase 1 dose escalation study using 4 × 10 7 , 1 × 10 8 or 4 × 10 8 CD30.CAR EBVSTs infused after lymphodepletion with cyclophosphamide and fludarabine...Thus banked CD30.CAR EBVSTs can safely be given to allogeneic recipients and may cause significant tumor responses including complete remissions. These cells may be a suitable platform for other “off-the-shelf” CAR-T cell therapies.

P1, N=66, Recruiting, Baylor College of Medicine | Trial primary completion date: Apr 2021 --> Apr 2022

P2, N=94, Recruiting, Tessa Therapeutics | Trial completion date: Aug 2024 --> Feb 2036

P1, N=21, Recruiting, Tessa Therapeutics | Trial completion date: Feb 2023 --> Mar 2036 | Initiation date: Nov 2020 --> Mar 2021 | Trial primary completion date: Feb 2022 --> Mar 2023

P2, N=94, Recruiting, Tessa Therapeutics | Not yet recruiting --> Recruiting

P1, N=21, Recruiting, Tessa Therapeutics | Not yet recruiting --> Recruiting

P2, N=90, Not yet recruiting, Tessa Therapeutics | Initiation date: May 2020 --> Dec 2020

P1/2, N=40, Recruiting, UNC Lineberger Comprehensive Cancer Center | Trial completion date: Feb 2037 --> Aug 2038 | Trial primary completion date: Feb 2022 --> Aug 2023

P1, N=21, Not yet recruiting, Tessa Therapeutics