Cavatak (gebasaxturev)

P1/2, N=146, Completed, Merck Sharp & Dohme LLC | Active, not recruiting --> Completed | N=90 --> 146

This study demonstrates the potential of CVA21 to modulate the immunogenicity of tumor cells and remodelling the tumor microenvironment, providing novel insights for patient selection for trials involving novel immunotherapeutic approaches.

P1/2, N=90, Active, not recruiting, Merck Sharp & Dohme LLC | Trial completion date: Apr 2030 --> Oct 2025 | Trial primary completion date: Apr 2030 --> Oct 2025

Here we report results from the first three arms: pembrolizumab plus vibostolimab (anti-TIGIT), pembrolizumab plus gebasaxturev (coxsackievirus A21) and pembrolizumab monotherapy. Longer follow-up will provide insight into the incremental benefit of combining neoadjuvant pembrolizumab with other therapies in stage IIIB-D melanoma. ClinicalTrials.gov registration: NCT04303169 .

In vitro, PD-H exhibited robust replication, as measured by plaque assays, and potent lytic activity, as assessed by XTT assays, in most pancreatic tumor cell lines, outperforming two other coxsackievirus strains tested, H3N-375/1TS and CVA21...Although pancreatic tumors respond to PD-H treatment, its therapeutic efficacy is limited. Combining PD-H with other treatments, such as those aiming at reducing the desmoplastic stroma which impedes viral infection and spread within the tumor, may enhance its efficacy.

Additionally, this platform allows us to investigate not only the contribution of processes related to the viral kinetics and dynamics on tumor response, but also the influence of its interaction with an ICI. Additionally, the model can be used to explore different scenarios aiming to optimize treatment combinations and support clinical development.

In addition, both recombinant interferon-gamma and pembrolizumab increased ICAM-1 on tumor cell lines or organoids and, in turn, amplified V937-mediated oncolysis and immunogenicity. These findings provide critical mechanistic insights on the cross-talk between V937-mediated oncolysis and immune responses, demonstrating the therapeutic potential of V937 in combination with PD-1 blockade to treat immunologically quiescent cancers.

P1/2, N=75, Terminated, Merck Sharp & Dohme LLC | Phase classification: P1b/2 --> P1/2 | Completed --> Terminated; Business Reasons

P2, N=85, Terminated, Merck Sharp & Dohme LLC | Completed --> Terminated; Business Reasons

The results of the current study suggest that MSCs loaded with oncolytic CVA21 therapy for the CRC mouse model may have some potential advantages. On the other hand, the results of the study showed that, in addition to activating the acquired immune system, the use of MSCs loaded with oncolytic CVA21 also stimulates the innate immune system by increasing levels of nitric oxide.

P1/2, N=90, Active, not recruiting, Merck Sharp & Dohme LLC | Recruiting --> Active, not recruiting

Given the relative safety and tolerability of oncolytic viruses, and the lack of reports of dose-limiting-dependent toxicities, more patients treated with T-VEC with or without ICIs should be added to future assessment analyses. There is still a long way to go before it can be used as a first-line therapy for patients with advanced or unresectable melanoma.