zamtocabtagene autoleucel (MB-CART2019.1)

P2, N=168, Recruiting, Miltenyi Biomedicine GmbH | Trial completion date: Dec 2024 --> Jul 2027 | Trial primary completion date: Dec 2023 --> Dec 2024

P2, N=110, Recruiting, Miltenyi Biomedicine GmbH | N=65 --> 110 | Trial completion date: Jun 2025 --> Dec 2026 | Trial primary completion date: Jul 2023 --> Dec 2024

P2, N=168, Recruiting, Miltenyi Biomedicine GmbH | Trial completion date: Sep 2024 --> Dec 2024 | Trial primary completion date: Sep 2023 --> Dec 2023

Sponsored By MILTENYI

P2, N=65, Recruiting, Miltenyi Biomedicine GmbH | Trial completion date: Sep 2024 --> Jun 2025 | Trial primary completion date: Oct 2022 --> Jul 2023

MB-CART2019.1 is manufactured without freeze-thaw cycles and intended to be infused as a fresh product (day 0) after lymphodepleting chemotherapy with fludarabine 30 mg/m2body surface area (BSA)/d and cyclophosphamide 300 mg/m2 BSA/d on day -5 to day -3 prior to MB-CART2019.1 infusion. The comparator treatment consists of R-GemOx (rituximab, gemcitabine and oxaliplatin) or Pola-BR (polatuzumab vedotin, bendamustine and rituximab), pre-defined to a maximum of 10% of enrolled patients...Safety endpoints include frequency and severity of adverse events as well as the use of tocilizumab and/or high-dose steroids...The study is actively enrolling patients since August 2021. In addition, MB-CART2019.1 is under development in the United States, and a separate pivotal Phase II trial is currently enrolling patients with r/r DLBCL who have failed at least two lines of prior systemic therapy (DALY 2.0 USA, NCT04792489).

All 12 MB-CART2019.1 DPs exhibited a consistent and reproducible expansion profile, high CD4:CD8 ratio, high TCM proportion and low expression of exhaustion markers. Increased proliferative ability in the DP, higher Cmax, as well as maintaining higher levels of TCM during in vivo expansion were characteristically elevated parameters of pts with CR. Other product characteristics, e.g. CD4:CD8 ratio or number of infused T-cells, were not significantly associated with in vivo performance.

P2, N=65, Recruiting, Miltenyi Biomedicine GmbH | Trial completion date: Apr 2024 --> Sep 2024 | Trial primary completion date: May 2022 --> Oct 2022

Fludarabine and cyclophosphamide were used for lymphodepletion. Importantly, all 5 pts with CR were still in CR 12 months after treatment and have now completed the 2-year follow-up visit without evidence of relapse. MB-CART2019.1 is currently challenging conventional immune-chemotherapy in a randomized Phase II trial for elderly, non-transplant eligible pts with first progression or relapse of aggressive B-NHL ( NCT04844866).

Safety endpoints include frequency and severity of adverse events as well as the use of tocilizumab and/or high-dose steroids...MB-CART2019.1 is infused as a fresh product (day 0) after a lymphodepleting chemotherapy regimen consisting of fludarabine 30 mg/m 2 body surface area (BSA) and cyclophosphamide 300mg/m 2 BSA (each from day -5 to day -3 prior to MB-CART2019.1 infusion). The comparator treatment consists of either R-GemOx (rituximab, gemcitabine and oxaliplatin) or BR (rituximab and bendamustine) plus polatuzumab vedotin, pre-defined to a maximum of 10% of enrolled patients...The study is actively enrolling patients since August 2021. Clinical trial information: NCT04844866.

P2, N=168, Recruiting, Miltenyi Biomedicine GmbH | Not yet recruiting --> Recruiting | Trial completion date: Jun 2024 --> Sep 2024 | Initiation date: Apr 2021 --> Aug 2021 | Trial primary completion date: Jun 2023 --> Sep 2023

P1/2, N=12, Active, not recruiting, Miltenyi Biomedicine GmbH | Trial completion date: Jul 2025 --> Dec 2025

P2, N=168, Not yet recruiting, Miltenyi Biomedicine GmbH

Fludarabine/cyclophosphamide lymphodepleting chemotherapy was administered from day -5 to -3...Tocilizumab was given in 1 patient...The sustained expansion of tandem CAR T-cells was accompanied by efficacy: all patients (6/6) treated on DL2 responded and all 5 patients with CR (5/5) are in ongoing remission by the time of this report. Based on the promising risk-to-benefit ratio observed in our study, evaluation of MB-CART2019.1 at a dose of 2.5x106/kg body weight in clinical phase II and phase III trials for patients with relapsed aggressive B-NHL is underway.

In this first-in-human dose finding study of MB-CART2019.1 no DLT occurred. Furthermore, no severe CRS or neurotoxicity and no grade 5 AE were observed. General feasibility and safety were very good in this cohort of elderly r/r B-NHL patients.

In this first-in-human dose finding study of MB-CART2019.1 no DLT occurred. Furthermore, no severe CRS or neurotoxicity and no grade 5 AE were observed. General feasibility and safety were very good in this cohort of elderly r/r B-NHL patients.

In this first-in-human dose finding study of MB-CART2019.1 no DLT occurred. Furthermore, no severe CRS or neurotoxicity and no grade 5 AE were observed. General feasibility and safety were very good in this cohort of elderly r/r B-NHL patients.

In this first-in-human dose finding study of MB-CART2019.1 no DLT occurred. Furthermore, no severe CRS or neurotoxicity and no grade 5 AE were observed. General feasibility and safety were very good in this cohort of elderly r/r B-NHL patients.

P1/2, N=12, Active, not recruiting, Miltenyi Biotec B.V. & Co. KG | Trial completion date: Mar 2025 --> Jul 2025 | Trial primary completion date: Sep 2019 --> Dec 2020 | Recruiting --> Active, not recruiting