On June 6, 2023 ImmVira reported four abstracts covering latest results from Phase I/II clinical trials of MVR-T3011 IT (intratumoral injection) and MVR-T3011 IV (intravenous injection) in both U.S. and China with all selected to be published (1 chosen for poster discussion) at the 2023 American Society for Clinical Oncology Annual Meeting (ASCO 2023) taking place from June 2nd to 6th, 2023 in Chicago, IL (Press release, Immvira, JUN 6, 2023, View Source [SID1234632531]).
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1. Intratumoral product MVR-T3011 IT demonstrated clinical efficacy both as monotherapy and combination therapy
1） Phase I/IIa study of MVR-T3011 IT administered via intratumoral injection in China as monotherapy
Being among the 22 China studies selected for Poster Discussions this year, MVR-T3011 IT clinical updates in China was also presented in a Poster discussion session on June 3rd (see below).
As of January 18, 2023, among 90 patients who received MVR-T3011 IT monotherapy, the most frequent treatment-related adverse events ("TRAEs") were pyrexia and no dose-limiting toxicity ("DLT") events were reported. Recommended Phase II dose ("RP2D") was determined to be 1×108 PFU/ml.
The confirmed objective response rate ("ORR") was 11% and disease control rate ("DCR") was 49% in 55 patients (with head and neck squamous cell carcinoma ("HNSCC"), sarcoma, melanoma, breast cancer, etc.) treated under RP2D evaluable for tumor response. 12 evaluable HNSCC patients who progressed after platinum-based chemotherapy and anti-PD-1/PD-L1 therapy achieved confirmed ORR of 25% and DCR of 50%, respectively.
Meanwhile, 69.2% of patients were observed with increases in tumor-infiltrating CD8+ cell density in biopsy collected at 8 weeks after the first dose. In particular, 3 head and neck cancer patients with partial response ("PR") had notable increases in tumor-infiltrating CD8+ cell density in biopsy.
Trial results showed that, MVR-T3011 IT had excellent safety profile and clinical compliance. The drug didn’t spread to blood, urine or saliva when injected intratumorally. Additionally, MVR-T3011 IT monotherapy demonstrated encouraging anti-tumor activity in advanced HNSCC patients, supporting further evaluation in Phase II studies.
2） Phase I/IIa study of MVR-T3011 IT administered via intratumoral injection in the U.S. as monotherapy and combination therapy combined with Pembrolizumab
As of January 17, 2023, among 29 patients who received MVR-T3011 IT monotherapy or in combination with pembrolizumab, most frequent TRAEs were pyrexia, and no additional safety signals were observed in combination therapy.
12 advanced melanoma patients failing prior PD-1 or PD-1/CTLA-4 combination treatment received MVR-T3011 IT monotherapy. The confirmed ORR and DCR were 25.0% and 33.3%, respectively. 6 patients (including 5 with melanoma and 1 with mesothelioma) were re-challenged with MVR-T3011 IT combined with pembrolizumab after progression on monotherapy, among which 1 patient achieved PR after 4 months and ongoing PR had lasted for more than 8 months as of the data cutoff date.
Meanwhile, remarkable increases in tumor-infiltrating CD8+ cell density in biopsy were observed in 66.7% of patients with PR or stable disease ("SD"). In particular, the increment of CD8+ cell density in 2 melanoma patients with PR was over 15 folds.
Trial results showed that, MVR-T3011 IT monotherapy and combination therapy with pembrolizumab were safe and tolerable. MVR-T3011 may modify tumor microenvironment and overcome immune resistance.
2. MVR-T3011 IV, global first intravenous oHSV product, showed assuring safety profile
As of December 16, 2022, a total of 15 patients (including 12 patients who received single ascending dose and 3 patients who received multiple ascending dose) received MVR-T3011 IV monotherapy with different dosages (1×106 PFU~3×108 PFU), all of which were Stage IV patients with chemotherapy history, including 9 patients who had received third-line or above treatment. Among them, 11 patients achieved SD, and the DCR was 73.3%. Notably, one colorectal cancer patient who progressed after irinotecan-based chemotherapy, anti-VEGF, and radiation therapy had long-term disease control with SD for over 4 months.
Among these patients, three had Grade 3 treatment emergent adverse events ("TEAE") in the Common Criteria for the Evaluation of Adverse Events ("CTCAE") (hypertriglyceridemia, dyspnea, lymphopenia), only one case of Grade 3 TRAE (lymphopenia) was reported, and no≥ Grade 4 adverse event ("AE") was reported. No drug-related Serious Adverse Event ("SAE") or DLT occurred; maximum tolerated dose ("MTD") was not reached.
Trial results showed that, MVR-T3011 IV is safe, well-tolerated, and unlikely to spread to close contacts. Encouraging preliminary efficacy and MVR-T3011 viral DNA in blood in a dose-dependent manner with additive effects from repeated doses support continued recruitment of patients to higher dose cohorts.
In the meantime, MVR-T3011 IV’s U.S. Phase I clinical data was also selected to be published at ASCO (Free ASCO Whitepaper) this year. We are expecting to report more intravenous clinical results in both U.S. and China in the future.
About MVR-T3011 IT and MVR-T3011 IV
MVR-T3011 IT and MVR-T3011 IV are two separate products developed on the same basis of MVR-T3011. MVR-T3011 IT is designed for intratumoral injection of solid tumors while MVR-T3011 IV is designed for intravenous injection and is also global first systemic administered oHSV in clinical stage. MVR-T3011, ImmVira’s proprietary 3-in-1 oHSV, is a novel genetic engineered oHSV which aims to achieve the most favorable profile of attenuated HSV-1 with replication potency in tumor cells and highly restricted replication in normal cells. In addition, MVR-T3011 carries two latest and well-validated exogenous genes, PD-1 antibody and IL-12, to further enhance immune responses of tumor microenvironment.