Initiation of triple immunization program clinical trial for PD-1/L1 monoclonal antibody treatment of drug-resistant prenabulin

Transfer from Pharmaceutical Mission Hills

On June 4, Wanchun Medicine announced that a Phase 1b/2 study of pranabulin combined with checkpoint inhibitors and radiotherapy at MD Anderson Cancer Center ushered in the first patient administration
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This is a three-drug combination clinical trial recently launched by Wanchun Medicine to solve the problem of drug resistance after PD-1/PD-L1 antibody treatment

It is reported that this trial was initiated by researchers to evaluate the safety and tolerability of pranabulin, PD-1/PD-L1 antibody and radiotherapy triple therapy in patients with 7 types of metastatic or locally advanced cancer Sex
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The seven types of cancers include non-small cell lung cancer (NSCLC), small cell lung cancer, renal cell carcinoma, bladder cancer, melanoma, Merkel cell carcinoma, and high-microsatellite instability (MSI-H) cancers (histologically variable) Limited)

Pranabrin is a selective immunomodulator that binds to microtubules.
It activates tumor antigen-specific T cells by inducing the maturation of dendritic cells to target and recognize cancer cells in a specific way
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Studies have shown that Pranabrin can trigger a high-intensity anti-cancer immune response

Wanchun Medicine demonstrated the concept of triple therapy at the AACR annual meeting held in 2020
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According to pre-clinical studies published earlier, Pranabrin has shown a key role in triple I/O therapy with PD-1 antibody and radiotherapy

Effectiveness study: In a breast cancer animal model that is resistant to PD-1 antibody monotherapy, the triple I/O regimen of prinabulin + PD-1 antibody + radiotherapy achieved 100% complete tumor remission (CR)
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Distal effect: When the anticancer effect of pranabulin triple therapy on chemotherapy-irradiated and unirradiated tumors (distal effect) was evaluated in the same mouse, the results showed a good distal effect, indicating that the systemic anticancer effect was activated.
Cancer immune response
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Moreover, the level of CD8 T cells in unirradiated tumors (distal tumors) in the triple therapy group was almost twice that of the PD-1 antibody and radiotherapy alone treatment group

This provides data support for the concept of triple therapy and clinical research
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Due to the reduced immune-related sensitivity observed in PD-1/PD-L1 antibody therapy, the potential of prinabulin demonstrated in preclinical studies is expected to alleviate this phenomenon and curb PD-1/PD-L1 therapy The disease progresses after failure, and the therapeutic effect of immunotherapy and radiotherapy is enhanced

Therefore, the goal of this trial is to allow those patients who developed drug resistance during PD-1/PD-L1 treatment to continue to receive the original immunotherapy, and to reverse their resistance to the original PD-1/PD-L1 through triple therapy.
Resistance of L1 therapy
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According to the trial plan, Pranabrin and 5 PD-1/PD-L1 immunotherapy drugs will be evaluated, including avelumab, duvalizumab, nivolizumab, atilizumab, and pembrolizumab The combination plan of monoclonal antibodies, and the exact dosage and dosing plan of each immunotherapy drug are determined according to the treatment cycle

Public information shows that Panabrin has completed 9 clinical trials around the world, including four phase 2 and 3 international multicenter clinical trials for neutropenia (CIN), and submitted them in China and the United States.

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