AACR24: Cancer vaccines find foothold in immunotherapy combos, relapse prevention

2024-04-11

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After falling out of favour following a series of clinical failures, cancer vaccines may have finally found their niches in the cancer treatment paradigm. Data presented at this year’s American Association for Cancer Research (AACR) annual meeting suggest cancer vaccines might be effective in treating later-stage patients in combination with established immunotherapies, and to prevent relapse.

Moderna notches second win

After demonstrating the potential of its personalised cancer vaccine to treat melanoma at last year’s American Society of Clinical Oncology (ASCO) meeting, Moderna shared Phase I data from a different tumour type at AACR, suggesting its versatility.

Moderna is partnered with Merck & Co. to develop mRNA-4157 (V940), an mRNA-based individualised neoantigen therapy that encodes up to 34 neoantigens inducing specific anti-tumour T-cell activation. In 22 patients with unresectable, metastatic HPV-negative head and neck squamous cell cancer (HNSCC), mRNA-4157 plus Merck's anti-PD-1 antibody Keytruda (pembrolizumab) led to a response rate of 27.3%.

The data was sufficient to add about 6% to Moderna’s market cap, one of the biggest gains seen by a biotech on the back of conference data. For more market analysis, see Vital Signs: AACR24’s most impactful market movers.

Keytruda combo success for Geneos

Geneos Therapeutics shared Phase I/II data of GT-30, a DNA plasmid encoded personalised therapeutic cancer vaccine (PTCV) that may include up to 40 neoantigens, as a second-line treatment for hepatocellular carcinoma patients who have previously received a multi-tyrosine kinase inhibitor multi-tyrosine kinase inhibitor.

In combination with DNA plasmid encoded IL-12 and Keytruda, the PTCV led to an observed response rate (ORR) of 30.6% in 36 evaluable patients, including three complete responses (CRs). Based on a 16.9% ORR historical benchmark for Keytruda monotherapy, GT-30 achieved a statistically significant response rate.

At the data cutoff, patients who received GT-30 had a median overall survival (OS) of 19.9 months compared with a historical OS range of 12.9 – 15.1 months for Keytruda.

"Other recent industry trials have tested personalised cancer vaccines in patients with highly immune-sensitive tumour phenotypes and no measurable disease. In marked contrast, the GT-30 trial assesses PTCVs in HCC, a cancer with very low tumour mutational burden and an immune-excluded phenotype, and in patients with significant late-stage unresectable and metastatic disease," said Geneos CEO Niranjan Sardesai. “We have not only met endpoints for safety, immunogenicity, and clinical efficacy based on ORR in this difficult-to-treat setting, but our mechanism of action data trace and confirm every step, from vaccination to tumour reduction, required to explain the immunological basis for the observed clinical responses."

Long-term data for Genentech, BioNTech

Vinod Balachandran, a surgical oncologist and researcher at the Memorial Sloan Kettering Cancer Center (MSKCC), presented three-year follow-up data from an MSKCC-sponsored Phase I trial of autogene cevumeran – an individualised mRNA vaccine from partners Genentech and BioNTech that targets up to 20 unique neoantigens identified from each patient’s tumour.

Of the 16 evaluable patients with resectable pancreatic cancer who received autogene cevumeran in combination with Roche’s PD-L1 inhibitor Tecentriq (atezolizumab) and modified FOLFIRINOX chemotherapy, half experienced induced immune responses, as measured by high-magnitude neoantigen-specific T-cell expansion.

After a median follow-up of three years, those eight patients with vaccine-induced T-cell responses had still not reached median recurrence-free survival, compared with 13.4 months for the eight patients whose immune systems did not respond to the cancer vaccine.

“The findings that individualised neoantigen-specific cancer vaccines can induce a robust immune response that correlates with delayed disease recurrence continues to support these vaccines as an encouraging therapeutic approach for pancreatic cancer,” Balachandran said.

Transgene seeks to delay relapse

Transgene developed TG4050, a personalised cancer vaccine that uses a nonpathogenic form of poxvirus to deliver 30 neoantigens, to delay relapse of surgically resected tumours.

In a Phase I trial of 33 patients with stage 3 or 4 surgically resected HPV-negative HNSCC who have also undergone standard-of-care radiation and chemotherapy, TG4050 induced tumour-specific immune responses and led to low rates of disease relapse.

Of the 17 patients who received the cancer vaccine immediately after standard of care, none relapsed after a median follow-up of 16.2 months. In the 16-patient observational arm, three experienced disease relapse: one after 6.2 months, another after 8.8 months, and a third after 18.5 months. Participants in the cohort are eligible to receive TG4050 following relapse.

All but one of the vaccinated patients showed evidence of activated neoantigen-specific T cells in response to TG4050, which was individualised for each patient using AI and machine learning tools to analyse their tumour’s genome and identify relevant mutations and immunogenic neoantigens.

“A therapeutic vaccine tailored to each patient’s unique tumour may lead to strong immune responses, which could eliminate any minimal residual disease that may eventually lead to disease relapse,” said Olivier Lantz, a clinical immunologist and researcher at Institut Curie in Paris.