The development of cancer vaccines has shown significant progress in recent years, with various studies exploring their efficacy and safety. Among the numerous phase I trials, a few stand out for their promising results in terms of response rates and disease-free survival. Below is an analysis of the most encouraging trials based on these parameters.
1. ELI-002 2P for KRAS-Mutated Pancreatic and Colorectal Cancers
In a phase 1 study, the cancer vaccine ELI-002 2P was evaluated for its efficacy in patients with KRAS-mutated pancreatic and colorectal cancers. This vaccine uses amphiphile (Amph) modification of KRAS peptides along with a CpG oligonucleotide adjuvant to enhance immune response.
- Response Rate: 84% of patients showed tumor biomarker responses, with biomarker clearance observed in 24% of patients.
- Disease-Free Survival: The median relapse-free survival (RFS) was 16.33 months.
This trial demonstrated substantial T cell responses, correlating with improved efficacy, suggesting that ELI-002 2P holds promise for treating KRAS-mutated tumors.
2. Personalized Therapeutic Cancer Vaccine (PTCV) for Hepatocellular Carcinoma (HCC)
A phase 1/2 study investigated a DNA plasmid PTCV encoding up to 40 neoantigens, combined with pembrolizumab, in patients with advanced HCC.
- Response Rate: The objective response rate was 30.6%, with 8.3% achieving a complete response.
- Disease-Free Survival: Specific data on disease-free survival were not provided, but clinical responses were linked to the number of neoantigens encoded in the vaccine.
The results indicate that the PTCV, when combined with pembrolizumab, induces significant antitumor T cell responses and shows clinical activity in advanced HCC.
3. BVAC-C for HPV-Positive Cervical Carcinoma
A phase IIa study assessed the efficacy of BVAC-C, an immunotherapeutic vaccine for patients with recurrent HPV 16- or 18-positive cervical cancer who had previously failed platinum-based chemotherapy.
- Response Rate: The objective response rate was 19.2%, with the highest response seen in Arm 1 (20%) and Arm 2 (33.3%).
- Disease-Free Survival: Data on disease-free survival were not explicitly provided.
BVAC-C showed a promising safety profile and antitumor activity, particularly in patients receiving the vaccine more frequently.
4. Chimeric Antigen Receptor (CAR) T Cells with RNA Vaccine for Solid Tumors
The BNT211-01 trial explored the safety and feasibility of CAR T cells targeting CLDN6, with or without a CAR-T cell-amplifying RNA vaccine, in patients with relapsed/refractory CLDN6-positive solid tumors.
- Response Rate: The unconfirmed objective response rate was 33%, including one complete response.
- Disease-Free Survival: Disease control rate was 67%, with stable disease in seven patients.
This trial highlighted the potential of combining CAR T cell therapy with an RNA vaccine to achieve manageable toxicity and robust engraftment, indicating promising clinical activity.
The most promising Phase II trials using vaccination for cancer based on response rates and disease-free survival are:
- ELI-002 2P Vaccine for KRAS Mutated Pancreatic and Colorectal Cancers
- Results: Treated 25 patients, with an 84% tumor biomarker response rate, 24% biomarker clearance, and a median relapse-free survival (RFS) of 16.33 months. Significant T cell responses and a substantial reduction in tumor biomarkers were observed.
- Highlights: Median tumor biomarker reduction was -76.0% with a median RFS not reached in the higher T cell response group.
- Conclusion: ELI-002 2P was safe and induced strong T cell responses, showing promise for patients with KRAS-mutated tumors.
- BVAC-C for HPV-Positive Cervical Carcinoma
- Results: Of the 30 patients analyzed, the overall response rate (ORR) was 19.2%, with disease control rates (DCR) of 53.8%. The ORR was higher in certain treatment arms, demonstrating potential efficacy.
- Conclusion: BVAC-C was well-tolerated and induced significant responses in patients with HPV-positive recurrent cervical carcinoma, showing potential for further development.
- DNA Vaccine (pTVG-HP) and Nivolumab for Prostate Cancer
- Results: In this trial, 21% of patients had a PSA decline of over 50%, with median PSA doubling times significantly increasing during treatment. No complete PSA responses were observed, but the vaccine showed potential in prolonging disease progression.
- Conclusion: The combination was safe and showed immunological activity, suggesting a potential role in early recurrent prostate cancer.
- Personalized Therapeutic Cancer Vaccine (PTCV) with Pembrolizumab for HCC
- Results: Objective response rate was 30.6% with 8.3% achieving complete response. Neoantigen-specific T cell responses were confirmed in 86.4% of evaluable patients.
- Conclusion: PTCV plus pembrolizumab demonstrated significant clinical activity in advanced HCC, supported by strong T cell responses and clonal expansion.