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Moderna, Inc. and Merck today announced distant metastasis-free survival (DMFS) results from the Phase 2b randomized KEYNOTE-942/mRNA-4157-P201 study, a clinical trial evaluating mRNA-4157 (V940), an investigational individualized neoantigen therapy (INT), in combination with KEYTRUDA, Merck's anti-PD-1 therapy, in patients with resected high-risk melanoma (stage III/IV).
In the overall intention-to-treat (ITT) population, adjuvant treatment with mRNA-4157 (V940) in combination with KEYTRUDA demonstrated a statistically significant and clinically meaningful improvement in DMFS, a key secondary endpoint of the study, compared with KEYTRUDA alone and reduced the risk of developing distant metastasis or death by 65% (HR=0.347 [95% CI, 0.145-0.828]); one-sided p value=0.0063).
The secondary endpoint of DMFS, defined as the time from the first dose of KEYTRUDA until the date of first distant recurrence or death from any cause, was pre-specified for statistical testing following the positive primary endpoint of recurrence-free survival.
"We are excited to share these results with the oncology community and thrilled to see such an exceptional result in distant melanoma recurrence or death. Patients who experience metastases at distant sites typically have worse survival outcomes and a poor prognosis, thus, these results showing a reduction in the risk of distant recurrence underscore the potential of neoantigen therapy," said Kyle Holen, M.D. Moderna's Senior Vice President and Head of Development, Therapeutics, and Oncology, in a press release on June 5, 2023.
Companies plan to initiate a Phase 3 study in the adjuvant setting in patients with high-risk melanoma in 2023 and rapidly expand to additional tumor types, including non-small cell lung cancer.
Based on data from KEYNOTE-942/mRNA-4157-P201, the U.S. Food and Drug Administration and European Medicines Agency granted Breakthrough Therapy Designation and the Priority Medicines scheme, respectively, for mRNA-4157 (V940) in combination with KEYTRUDA for the adjuvant treatment of patients with high-risk melanoma following complete resection.
Transgene today announced that new data confirm the ability of this novel investigational therapeutic cancer vaccine to induce immune responses against human papillomavirus (HPV) 16 antigens that are associated with antitumor response.
TG4001 is an investigational viral vector-based therapeutic cancer vaccine.
It is being evaluated in a randomized controlled Phase II clinical study comparing TG4001 with avelumab to avelumab alone in patients with HPV16-positive anogenital tumors.
The data presented on June 5, 2023, were generated from 46 patients in both trial arms.
- TG4001 induced the priming of adaptive immunity
- 58% of patients receiving TG4001 + avelumab showed an increase of immune responses against HPV antigens versus 9% in the avelumab arm. At baseline, immune responses against HPV antigens were limited to 4/46 patients.
- An immune response was detected at day 43 and tended to increase intensity at day 85.
- These data demonstrate that Transgene's TG4001 could induce a specific immune response against the antigens vectorized within this vaccine.
- 11 of the 13 patients with an immune response had either stable disease, partial or complete tumor response according to RECIST criteria.
- Remarkably, two case studies are presented, with patients exhibiting a strong E6 and E7 immune response while showing a complete clinical response.
- Transgene anticipates that the last patient will be randomized in the current Phase II clinical study in the first half of 2024. The final results will be communicated in 2024.
Dr. Alessandro Riva, MD, Chairman and CEO of Transgene, commented in a press release, "These data further confirm that our therapeutic vaccine TG4001 can induce clinically meaningful immune responses that are associated with antitumor response."
The abstract and poster can be accessed on the ASCO and Transgene websites.
TG4001 is an investigational therapeutic vaccine based on a non-propagative, highly attenuated Vaccinia vector, which is engineered to express HPV16 antigens (E6 & E7) and an adjuvant (IL-2).
TG4001 was designed to have a two-pronged antiviral approach: to alert the immune system specifically to cells presenting the HPV16 E6 and E7 antigens that can be found in HPV16-related tumors and to further stimulate the infection-clearing activity of the immune system through interleukin 2 (IL-2).
HPV is a group of more than 200 related viruses, some of which are spread through sex. Researchers previously confirmed that infection with HPV16 precedes the development of some head and neck cancers.
Other HPV cancer vaccine news is posted by Precision Vaccinations.
Nykode Therapeutics ASA today announced that it had expanded the clinical collaboration and supply agreement with Roche to cover the evaluation of VB10.16, an off-the-shelf therapeutic cancer vaccine candidate in development for the treatment of human papillomavirus type 16 (HPV16)-positive cancers.
This collaboration, unveiled on June 1, 2023, is evaluating the combination with Roche’s cancer immunotherapy atezolizumab in patients with advanced cervical cancer who have progressed on pembrolizumab plus chemotherapy +/- bevacizumab as first-line treatment.
The VB-C-04 clinical trial is expected to be initiated in the U.S. in the fourth quarter of 2023 with registrational intent, which provides a potential fast-to-market path.
“We look forward to expanding our collaboration with Roche to bring the combination of VB10.16 and atezolizumab to cervical cancer patients with limited treatment options. Cervical cancer has a poor prognosis, and the recent positive clinical data from VB-C-02 has strengthened our commitment to contribute to a well-tolerated treatment that can potentially prolong the life of these women. The trial provides a potential fast path to market for VB10.16,” commented Michael Engsig, CEO of Nykode Therapeutics, in a press release.
Precision Vaccinations post other cervical cancer vaccine updates.
Southern Africa is again weathering a season of cholera, with six countries in the region recording outbreaks in 2023, reported Derick Matsengarwodzi with GAVI.
As of May 25, 2023, Malawi is the worst affected, recording 36,943 cases and 1,210 associated deaths between March 2022 and February 2023, according to World Health Organization (WHO).
So far this year, Malawi has received three shipments of oral cholera vaccine (OCV) in response to applications to the Gavi-supported stockpile established in 2013.
The latest 1.4 million OCV dose shipment arrived in Lilongwe in April 2023.
On May 22, 2023, Gavi published a roadmap outlining critical actions needed to ensure the supply of OCV can meet growing demand from countries.
The roadmap describes how these organizations, manufacturers, and countries can work together towards ensuring global OCV supply can support large-scale preventive vaccination by 2026.
"Cholera vaccines have steadily become more available over the past decade, meeting rising country demand," said Dr. Derrick Sim, Managing Director for Vaccine Markets and Health Security at Gavi, in a media release.
"As a result, the good news is we have doses to meet all emergency demand despite the rise in outbreaks, which is expected to continue. But this trend underscores the increasing importance of preventing outbreaks before they occur."
"The ultimate solution to both sustainable OCV supply and cholera control lies in our collective ability to step up our efforts on prevention programs."
As of May 31, 2023, various cholera vaccines have been approved but remain in limited supply.
Note: The U.S. CDC recently issued an Alert Level 2, Practice Enhanced Precautions, regarding polio outbreaks, which includes Malawi.
Immorna today announced that the first subject had been dosed in the Company's First-In-Human Phase 1 multi-center study of JCXH-105, a self-replicating RNA (srRNA) vaccine being developed for the prevention of Shingles.
The U.S. Food and Drug Administration (FDA) cleared its investigational new drug application on January 9, 2023, to conduct a Phase 1 multi-center study of JCXH-105.
NgocDiep Le, M.D., Ph.D., Global Chief Medical Officer of Immorna, commented in a press release on May 30, 2023, "If proven successful in clinical studies, JCXH-105 may become a valuable alternative to current standard-of-care to meet the large world-wide medical need for Shingles prevention."
"Due to its self-replicating nature, JCXH-105 may be effective at a significantly reduced dose level compared to non-replicating conventional mRNA vaccines and thereby may cause less reactogenicity and substantially reduce the cost of production."
"In addition, due to the synthetic nature of all JCXH-105 vaccine components, there are no raw material limitations or production bottlenecks."
This Phase 1 study is a randomized, double-blinded, multi-center, active-controlled study to assess the safety, immunogenicity, and determine the Recommended Phase 2 Dose for JCXH-105 for seniors.
In this study, JCXH-105 will be compared to GSK's U.S. FDA-approved Shingrix® vaccine.
Other shingles vaccine development news is posted by Precision Vaccinations.
After a lull of nearly two months throughout the country, the resurgence of avian influenza (bird flu) in France's South West in May 2023 has triggered an immediate response.
Reuters reported on May 26, 2023, France announced an avian influenza (bird flu) vaccination program would launch in late 2023.
Marc Fesneau, Minister of Agriculture and Food Sovereignty, called on May 22, 2023, for all avenues to be explored to improve the fight against highly pathogenic avian influenza (HPAI), foremost among which is vaccination.
On April 6, 2023, France launched a tender for 80 million doses of bird flu vaccines.
Temporary authorization for use has recently been submitted for vaccines for poultry species currently being assessed by the French Agency for Veterinary Medicinal Products and the European Medicines Agency.
To date, only one vaccine for chickens (Gallus gallus species) has marketing authorization in France (2006).
In the U.S., the Department of Agriculture's Agricultural Research Service recently confirmed they are testing several bird flu vaccine candidates. On May 16, 2023, the emergency use of an HPAI vaccine candidate to prevent additional deaths of California Condors.
Additional avian and human bird flu vaccine development news as of May 27, 2023, is posted by Precision Vaccinations.
According to Japan's National Institute of Infectious Diseases reported on May 14, 2023, the number of syphilis patients totaled 5,164 in 2023. The data for the same period in 2022 was 3,630.
The IDWR Surveillance Data Table week #19 confirmed Tokyo had the most cases at 1,332, followed by Osaka with 699 cases and Fukuoka with 257 cases.
According to the Institute, cases of congenital syphilis have been increasing in recent years, with 20 cases reported in 2022. In 2023, six patients were confirmed by early April.
Congenital syphilis is caused by the bacterium Treponema pallidum, which can be passed from mother to child during fetal development or at birth. Up to half of all babies infected with syphilis in the womb die shortly before or after birth.
"There is a possibility that cases of congenital syphilis will increase along with those of syphilis," commented Prof. Satoshi Takahashi, who heads the Japanese Society for Sexually Transmitted Infections, according to local media on May 24, 2023.
"Syphilis is a curable disease, so people should get tested without hesitation if they have worrisome symptoms or concerns."
As of April 11, 2023, the U.S. Centers for Disease Control and Prevention reported 176,713 syphilis cases in 2021 and 2,855 congenital syphilis cases, resulting in 220 stillbirths and infant deaths, a YOY increase of 32%.
Unfortunately, the U.S. Food and Drug Administration has not approved a syphilis vaccine as of May 27, 2023.
Biofabri and IAVI recently announced signing an agreement for the end-to-end development of tuberculosis (TB) vaccine candidate MTBVAC. This agreement provides a framework for the future collaboration that the partners first announced in 2021.
After securing sufficient funding, IAVI plans to begin an efficacy clinical trial in 2024.
MTBVAC is a highly promising vaccine candidate that has the potential to be used as an alternative to BCG vaccination in infants and for the prevention of TB disease in adolescents and adults.
"The world urgently needs a new, effective vaccine that can prevent TB disease in adults, adolescents, and infants," said Dr. Mark Feinberg, president, and CEO of IAVI, in a press release on May 17, 2023.
"We are honored to work with Biofabri and our other collaborators to advance MTBVAC."
"In addition, we are actively seeking the support of global health funders and other partners, public and private, to ensure that this promising vaccine candidate has the potential to be part of a solution to ending the TB epidemic."
Should MTBVAC be safe and efficacious, Biofabri will ensure that the TB vaccine is manufactured and supplied in sufficient quantities globally and is accessible at affordable prices in low- and middle-income countries.
Precision Vaccinations post other TB vaccine and outbreak news.
