Therapy Areas: Vaccines
Moderna Presents Interim Data from Phase 1 Study of mRNA Personalised Cancer Vaccine at 2019 ASCO Annual Meeting
5 June 2019 - - US-based clinical-stage biotechnology company Moderna, Inc., (NASDAQ: MRNA) has presented interim data from an ongoing Phase 1 clinical study in patients with both resected (adjuvant) and unresected (advanced) solid tumors, the company said.
The data showed that the company's mRNA personalized cancer vaccine mRNA-4157, given alone or in combination with Merck's pembrolizumab (KEYTRUDA), was well-tolerated at all doses tested and elicited neoantigen-specific T-cell responses.
There were no vaccine-related serious adverse events reported for the PCV when administered to patients as a monotherapy or in combination with pembrolizumab.
Presented at the 2019 American Society of Clinical Oncology (ASCO) annual meeting, the study demonstrates the immunogenicity of Moderna's mRNA platform for developing PCVs.
In addition, clinical activity was observed in some patients receiving mRNA-4157 in combination with pembrolizumab.
These safety, tolerability and immunogenicity data and the initial clinical activity observed support Moderna's randomised Phase 2 study investigating pembrolizumab in combination with a 1 mg dose of mRNA-4157, compared to pembrolizumab alone, for the treatment of high-risk adjuvant melanoma.
mRNA-4157 was well-tolerated at all dose levels studied with no dose-limiting toxicities or grade 3/4 adverse events or SAEs reported when administered as a monotherapy or in combination with pembrolizumab. The most common grade 2 adverse events were fatigue, soreness at the injection site, colitis and myalgias.
A cohort of patients at the top dose level are undergoing apheresis and deeper characterization of immunogenicity responses.
Data from one such patient was available at the data cutoff and showed neoantigen-specific CD8 T-cell responses were detected to 10 out of 18 class I neoantigens after the 4th dose of the vaccine (compared to 0/18 at baseline).
Clinical responses (one complete response + five partial responses) at doses ranging from 0.04-1.0 mg were observed in 6 out of 20 patients receiving at least one dose of mRNA-4157 in combination with pembrolizumab.
The complete response occurred to pembrolizumab monotherapy before mRNA-4157 was administered. Of the five partial responses, two were seen in patients previously treated with a checkpoint inhibitor.
Of the 13 patients who received adjuvant mRNA-4157 monotherapy, all patients have completed a full course of vaccination per the study protocol. Eleven patients remained disease free up to 75 weeks on study.
Additionally, the National Cancer Institute presented early data TODAY from its Phase 1 study of PCV mRNA-4650 as a monotherapy for patients with advanced metastatic cancers.
The NCI program uses Moderna's mRNA technology but uses a different neoantigen selection process and study design than Moderna's Phase 1 mRNA-4157 study.
Moderna's oncology programmes are currently focused on two main areas: cancer vaccines and intratumoral immuno-oncology therapies. Moderna is developing these potential mRNA treatments as monotherapies and/or in combination with checkpoint inhibitors from our strategic collaborators Merck and AstraZeneca.
The company currently has five I/O programmes in development, including two programs advancing into Phase 2 trials.
An advantage of Moderna's mRNA platform is that it allows for investigational medicines that combine in a single mRNA therapy several different approaches to activate the immune system to attack cancer, either with mRNA encoding for common tumor proteins found across cancer types or multiple mRNAs encoding for various immunomodulatory proteins.
Moderna's investigational PCVs are designed to use neoantigens identified from an individual's tumor to program the body's immune system to elicit a more effective anti-tumor response.
Upon sequencing the tumor, Moderna's proprietary algorithms predict the neoantigens (antigens encoded by tumor-specific mutated genes) most likely to trigger the immune system to attack a particular cancer. Today, mRNA encoding up to 34 unique neoantigens can be delivered in a single vaccine.
Moderna develops and manufactures these investigational PCVs at its personalized vaccines unit within its Norwood, Mass. manufacturing facility.
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