Off-the-Shelf Cervical Cancer Vaccine Shows Promising Initial Results in HPV16+ Patients

VB10.16, a first-in-class, off-the-shelf therapeutic cancer vaccine, yielded promising initial responses in patients with HPV16-positive advanced cervical cancer who were heavily pretreated and who were also receiving atezolizumab (Tecentriq), according to interim results from the phase 2 VB C-02 trial (NCT04405349) that were announced by Nykoke Therapeutics.¹

At a median follow-up of 6 months in 39 patients, data showed VB10.16 plus atezolizumab elicited an overall response rate (ORR) of 21%, including a complete response (CR) in 2 patients and a partial response (PR) in 6 patients. The disease control rate (DCR) was 64%.

“These interim results support Nykode’s unique approach of targeting antigen-presenting cells (APCs), designed to produce a robust and long-lasting CD8 killer T-cell response against cancer cells. We look forward to reporting updated efficacy data readouts from the phase 2 trial during the first half of 2023 as we continue to advance our cervical cancer program,” Michael Engsig, chief executive officer of Nykode Therapeutics, stated in a press release.

The single-arm, multicenter, open-label VB C-02 trial enrolled female patients who were at least 18 years of age with advanced or recurrent nonresectable HPV16-positive cervical cancer, including squamous cell carcinoma, adenosquamous carcinoma, or adenocarcinoma. Patients were required to have failed or be ineligible for systemic chemotherapy, radiotherapy, or other standard-of-care treatment.²

Other eligibility criteria included a biopsy to assess PD-L1 status at screening; measurable disease per RECIST v1.1 criteria; recovery from the effects of surgery, radiation therapy, or chemoradiotherapy; an ECOG performance status of 0 or 1 at screening; and a life expectancy of at least 6 months per the best judgement of the investigator.

The primary end points of the study were incidence and severity of adverse effects (AEs), and ORR per RECIST v1.1 criteria. Secondary end points include duration of response, progression-free survival (PFS), overall survival, and the evaluation of immunogenicity of VB10.16 in combination with atezolizumab by analyzing HPV16 E6/E7-specific cellular immune responses.

Additional data from the interim results showed VB10.16 and atezolizumab elicited responses irrespective of PD-L1 status. In patients with PD-L1–positive disease, the ORR was 27% with a DCR of 77% compared with an ORR of 17% with a DCR of 58% in patients with PD-L1–negative disease. Patients with non-inflamed tumors had a DCR of 71%.

Per the press release, immunological analyses of the peripheral T-cell responses showed an increased HPV16-specific IFNγ T-cell immune response following vaccination in most subjects. These responses were associated with clinical efficacy, and the clearance of circulating HPV16 DNA was significantly correlated with clinical response and PFS, pointing to circulating tumor DNA as an early marker of response to treatment in cervical cancer.

After previously reporting positive interim safety data from the trial, this interim data found VB10.16 was generally safe and well tolerated. Notably, 10% of patients experienced grade 3 or higher treatment-related AEs, indicating no increased toxicity compared with atezolizumab monotherapy.

“The patients who were treated with VB10.16 in combination with atezolizumab in the C-02 trial were heavily pretreated and are prone to progress quickly. It is very encouraging to see that a majority of patients experienced a clinical benefit and that many patients had durable responses. The combination of VB10.16 and atezolizumab was also well tolerated by patients,” principal trial investigator Peter Hillemanns, MD, PhD, director of the Departments of Gynecology, Obstetrics and Breast Cancer at Hannover University Hospital in Germany, stated in a press release.

The VB C-02 trial is fully enrolled to date, with 52 patients across Europe.

References

1. Nykode Therapeutics announces positive interim results from its phase 2 trial with VB10.16 in combination with immune checkpoint inhibitor atezolizumab in advanced cervical cancer. News release. Nykode Therapeutics. May 9, 2022. Accessed May 10, 2022. https://bit.ly/38cY98o
2. Investigating the combination of VB10.16 and atezolizumab in patients with HPV 16-positive cervical cancer. ClinicalTrials.gov. Updated February 23, 2022. Accessed May 10, 2022. https://clinicaltrials.gov/ct2/show/NCT04405349