Â鶹ӳ»­

• Cancer patients who received mRNA COVID vaccines within 100 days of starting immunotherapy were twice as likely to be alive three years after treatment as those who never received a vaccine
• These findings have prompted a randomized Phase III trial to determine if mRNA COVID vaccines should be part of the standard of care for this type of therapy
• If validated, findings could significantly increase the number of patients who benefit from immunotherapy

BERLIN, OCTOBER 19, 2025 ¨D Patients with cancer who received mRNA-based COVID vaccines within 100 days of starting immune checkpoint therapy were twice as likely to be alive three years after beginning treatment, according to a new study led by researchers at Â鶹ӳ»­ MD Anderson Cancer Center.

These findings, which include more than 1,000 patients treated between Aug. 2019 and Aug. 2023, were presented at the () and published in . The study was led by professor of Radiation Oncology, and Adam Grippin, M.D., Ph.D.,?senior resident in Radiation Oncology.

¡°This study demonstrates that commercially available mRNA COVID vaccines can train patients¡¯ immune systems to eliminate cancer,¡± Grippin said. ¡°When combined with immune checkpoint inhibitors, these vaccines produce powerful antitumor immune responses that are associated with massive improvements in survival for patients with cancer.¡±

How was this association discovered?

The discovery that mRNA vaccines were powerful immune activators came from research conducted by Grippin during his graduate work at the University of Florida in the lab of Elias Sayour, M.D., Ph.D. While developing personalized mRNA-based cancer vaccines for brain tumors, Grippin and Sayour found that mRNA vaccines trained immune systems to eliminate cancer cells, even when the mRNA didn¡¯t target tumors directly.

This finding led to the hypothesis that other types of mRNA vaccines might have the same effect, and the approval and use of mRNA-based COVID vaccines created an opportunity to test this hypothesis. Lin and Grippin initiated a major effort to retrospectively study if MD Anderson patients who received mRNA COVID vaccines lived longer than those who did not receive these vaccines.

How do mRNA COVID vaccines impact immunotherapy responses in cancer?

To better understand the mechanisms at work that can help explain the clinical data, the Lin and Sayour labs at both institutions studied preclinical models. They discovered that mRNA vaccines work like an alarm, putting the body¡¯s immune system on high alert to recognize and attack cancer cells.

In response, the cancer cells start making the immune checkpoint protein PD-L1, which works as a defense mechanism against immune cells. Fortunately, several immune checkpoint inhibitors are designed to block PD-L1, creating a perfect environment for these treatments to unleash the immune system against cancer.

These preclinical observations held up in clinical studies as well. The investigators found similar mechanisms, including immune activation in healthy volunteers and increased PD-L1 expression on tumors in patients who received COVID mRNA vaccines.

While the mechanisms are not yet fully understood, this study suggests COVID mRNA vaccines are powerful tools to reprogram immune responses against cancer.

What are the major implications of this discovery?

¡°The really exciting part of our work is that it points to the possibility that widely available, low-cost vaccines have the potential to dramatically improve the effectiveness of certain immune therapies,¡± Grippin said. ¡°We are hopeful that mRNA vaccines could not only improve outcomes for patients being treated with immunotherapies but also bring the benefits of these therapies to patients with treatment-resistant disease.¡±

A multi-center, randomized Phase III trial currently is being designed to validate these findings and investigate whether COVID mRNA vaccines should be part of the standard of care for patients receiving immune checkpoint inhibition.

What are the key data from this study on mRNA COVID vaccines and immunotherapy outcomes?

This study included multiple cohorts of several cancer types, evaluating patients who had received an mRNA vaccine within 100 days of starting immunotherapy treatment.

In the first group, 180 patients with advanced non-small cell lung cancer who received a vaccine had a median survival of 37.33 months, compared to 20.6 months in 704 patients who did not receive a vaccine. In a cohort of patients with metastatic melanoma, median survival was 26.67 months in 167 patients who did not receive a vaccine, but it had not yet been reached in 43 patients receiving a vaccine ¨C suggesting a significant improvement.

Importantly, these survival improvements were most pronounced in patients with immunologically ¡°cold¡± tumors, which would not be expected to respond well to immunotherapy. These patients, who have very low PD-L1 expression on their tumors, experienced a nearly five-fold improvement in three-year overall survival with receipt of a COVID vaccine.

Findings were consistent even when considering independent factors, such as vaccine manufacturer, number of doses, and when patients received treatment at MD Anderson.

***

This study was supported by the National Institutes of Health and National Cancer Institute, the Food and Drug Administration, the American Brain Tumor Association, the Radiological Society of North America, Conquer Cancer Foundation of ASCO, CureÂ鶹ӳ»­ for Children¡¯s Cancer, Stop Children¡¯s Cancer/Bonnie R. Freeman Professorship for Pediatric Oncology Research, Danny¡¯s Dream, Ian¡¯s Friends Foundation Inc., Alex¡¯s Lemonade Stand Foundation, The Medulloblastoma Initiative and Cure Group 4 Consortium, and the National Pediatric Cancer Foundation. For a full list of collaborating authors, disclosures and funding sources, ?or see the full paper in

• Lung cancer is the leading cause of cancer-related death worldwide, with up to 4% of non-small cell lung cancer cases having a HER2 gene mutation.

• Sevabertinib is an oral drug targeting HER2 mutations that shrinks tumors in advanced lung cancer patients, with minimal side effects.?

• FDA granted priority review for sevabertinib, and results of this study will help inform the decision.??

BERLIN, OCTOBER 17, 2025 ¨C The oral targeted therapy sevabertinib led to tumor reduction and manageable side effects in patients with HER2-mutant non-small cell lung cancer (NSCLC), according to data from a trial led by researchers at Â鶹ӳ»­ MD?Anderson Cancer Center.?

The Phase I/II?SOHO-01 clinical trial found that over 70% of the patients studied saw their tumors shrink or disappear. The results were published today in the and presented concurrently at the () by principal investigator , associate professor of Thoracic/Head and Neck Medical Oncology.

Why is the SOHO-01 study important??

While platinum-based chemotherapy and, in some cases, immunotherapy are the standard first-line treatments for patients with advanced HER2-mutant NSCLC, opportunities remain to improve outcomes and minimize toxicity with new targeted therapies.?

One such therapy, trastuzumab deruxtecan, a HER2-targeted antibody-drug conjugate (ADC), has received Food and Drug Administration (FDA) accelerated approval for patients who have already been treated. However, this treatment comes with health risks, including interstitial lung disease (ILD).?

The trial results suggest sevabertinib, a reversible tyrosine kinase inhibitor developed by Bayer ¨C targeting mutant HER2 while avoiding effects on normal EGFR ¨C may be a safe and effective option for this patient group.?

¡°For patients with HER2-mutant lung cancer, treatment options have historically been limited and outcomes suboptimal,¡± Le said. ¡°FDA approval of sevabertinib would introduce another targeted therapy option, one that precisely targets this mutation. This drug has demonstrated meaningful clinical activity with a manageable safety profile, representing a significant advance in the care of this challenging disease.¡±

What are the key findings of the Phase I/II?SOHO-01 trial??

The open-label, multicenter SOHO-01 study enrolled 209 patients with advanced NSCLC driven by EGFR or HER2 into three different cohorts, each receiving 20 mg. of sevabertinib twice a day. Cohort D included 81 patients who had received prior therapy not targeted to HER2; Cohort E included 55 patients who had received HER2-targeted ADCs; and Cohort F enrolled 73 patients who had not received prior therapies.?

The results demonstrated sevabertinib reduced tumor activity in patients both na?ve to and previously treated with HER2-targeted antibody-drug conjugates. Diarrhea was the most common side effect, and no ILD was reported.

Of the subgroups, Cohort D patients had a response rate of 70.5%, with a median time of 8.3 months before their cancer progressed. Encouragingly, similar results were seen across different patient cohorts, no matter which treatments they¡¯d had before or whether their cancer had spread to the brain.

Is sevabertinib currently approved for use in NSCLC patients??

In May 2025, sevabertinib was granted priority review for accelerated approval by the FDA. This came after it received the FDA¡¯s 2024 Breakthrough Therapy designation. The results of SOHO-01 support the New Drug Approval (NDA) submitted to the FDA.

***

This study was funded by Bayer AG. For a full list of collaborating authors, disclosures and funding sources, read the full paper in the

• VT3989 is a first-in-class YAP-TEAD inhibitor from Vivace Therapeutics that is currently in Phase I/II trials for patients with advanced solid tumors, with a focus on refractory mesothelioma
• In this trial, VT3989 demonstrated notable antitumor activity, with a disease control rate of 86% at the clinically optimized dosing levels
• These data provide the first clinical proof-of-concept for effectively drugging the Hippo-YAP-TEAD pathway
• VT3989 was awarded Orphan Drug Designation and Fast Track Designation for the treatment of mesothelioma by the FDA

BERLIN, OCTOBER 19, 2025 ¨D The first-in-class YAP-TEAD inhibitor VT3989 continued to be well tolerated and demonstrated notable initial antitumor activity, particularly in patients with refractory mesothelioma, according to results from a trial led by researchers from Â鶹ӳ»­ MD Anderson Cancer Center.

Data from the Phase I/II trial were presented today by , professor of Investigational Cancer Therapeutics and vice president and head of clinical development of MD Anderson¡¯s Therapeutics Discovery division, at the (Abstract ) and published simultaneously in

What are the notable results of this study evaluating VT3989?

The trial enrolled 172 patients, including 135 with refractory mesothelioma. Of the 22 mesothelioma patients treated with the optimized dose levels, seven had partial responses and 12 had stable disease ¨C a disease control rate of 86%. All 22 mesothelioma patients had previously received immunotherapy, and 82% had previously received chemotherapy.

¡°This study has multiple important takeaways, including the demonstration of significant disease control even in this heavily pretreated population,¡± Yap said. ¡°The safety profile was also encouraging, with mainly low-grade adverse effects. These data were strong enough to support the continued clinical development of VT3989 in mesothelioma, and we look forward to the next clinical study of the compound.¡±

How does VT3989 work?

This trial of VT3989 represents the first clinical proof-of-concept for inhibiting part of an important signaling pathway that regulates cell growth and immune response. This pathway is known as the Hippo signaling pathway and, within this pathway, the yes-associated proteins (YAP) work with transcriptional enhancer activator domain (TEAD) proteins.

In several cancer types, YAP is overexpressed or overactivated due to dysfunction in the pathway, which fuels cancer growth. VT3989 inhibits a specific modification on the TEAD protein, which blocks YAP function. Hence, VT3989 is known as a YAP-TEAD inhibitor.

Why is this being studied in mesothelioma patients?

Cancers with NF2 gene mutations are particularly dependent on the YAP-TEAD pathway. The NF2 gene encodes a protein called Merlin, and NF2 gene mutations/Merlin protein loss are common in mesothelioma patients.

Additionally, mesothelioma is a cancer that is very difficult to treat, and there are currently limited options for patients who do not respond to first-line treatments, making this a major unmet clinical need.

Previous trial updates

Initial data from this trial were presented at the American Association for Cancer Research (AACR) Annual Meeting 2023, demonstrating encouraging Phase I results.

***

This trial is funded by Vivace Therapeutics. A full list of authors and their disclosures can be found in the full paper in and in the