PDS0101 Plus Chemoradiation Elicits 100% ORR in High-Risk Locally Advanced Cervical Cancer

PDS0101 given in conjunction with chemoradiation elicited an 100% overall response rate (ORR), along with tumor shrinkage greater than 60%, in 9 patients with high-risk, locally advanced cervical cancer, according to results of the phase 2 IMMUNOCERV trial (NCT04580771) that were presented during the 2022 SITC Annual Meeting.^1,2

Specifically, the ORR was comprised of 8 complete responses and 1 partial responses. Eight of the 9 patients who completed treatment were alive at the time of data cutoff. The greater than 60% tumor shrinkage was observed at mid-point evaluation by MRI.

Moreover, the 1-year disease-free survival and 1-year overall survival rates were both 89%.

“The updated data from the ongoing IMMUNOCERV phase 2 clinical trial presented during SITC 2022 add to the encouraging results observed thus far and suggest that the combination of PDS0101 and CRT may hold promise as a potential first-line treatment for advanced, localized cervical cancer,” Frank Bedu-Addo, MD, CEO of PDS Biotech, the developer of PDS0101, stated in a news release.² “Importantly, 100% of patients responded to treatment with the combination of PDS0101 and CRT. We believe this study also provides further confirmation that PDS0101 induces the right type, quality, and potency of killer T cells in humans that may translate to effective treatment of cervical cancer.”

The company added that it plans to report additional data from the trial in 2023.

Human papillomavirus (HPV) cancers are said to be uniquely antigenic with expression of the E6 and E7 proteins. Radiation is a standard treatment for patients with locally advanced HPV-associated cancers, such as cervical cancer. Therefore, investigators theorize that radiation may synergize with immunotherapy and stimulate T-cell–mediated antitumor effects by increasing T-cell flux in tumors; it also promotes pathways that result in increased antigen presentation.

In the single-arm, phase 2 trial, investigators are combining PDS101, which is a subcutaneous E6/7 HPV16 T-cell–activating immunotherapy, with chemoradiation for patients with locally advanced squamous cell cervical cancer with either lymph node metastasis or tumors greater than 5 cm.

Thirty-five patients are planned for the study and 17 have enrolled, with 9 having completed treatment. The main outcome measures were efficacy and safety.

T0, T1, T2, T3, T4, T4B, and T5 were all assessed for HPV16-specific immune responses by measuring CD8-positive tumor-infiltrating lymphocytes, circulating tumor (ct)HPV DNA in peripheral blood, and comparing intratumoral T-cell receptor diversities.

PDS0101 was given subcutaneously in conjunction on days -14, 7, 28, 49, and 170 for a total of 5 doses.

The mean age at diagnosis was 42.2 years (range, 26-65), and patients had either HPV16 (66.7%), HPV18 (22.2%), or other (11.1%). Most patients (66.7%) received 5 doses of PDS0101 while the rest received 3. Moreover, 66.7% of patients had poor-differentiated tumors vs moderately differentiated (33.3%), and 2 patients (22.2%) had lymphovascular space invasion. More than half (55.6%) of patients had FIGO stage III disease, and all patients had node-positive tumors.

Regarding safety, grade 1/2 AEs included local injection site reactions (n = 7). One patient died due to a cardiac event.

Additional data showed that CD69 activation in CD8 T cells increased throughout treatment. CD9 expression peaked at T4; interferon-gamma decreased in T3 and increased at T4 and T5. In the assessment of ctDNA, it was found that ctHPV16 DNA in plasma increases at T1 and T2 before dropping in T3. TCR clonality did not change throughout treatment, and T-cell diversity was to be highest at the T4B following brachytherapy.

In June 2022, the FDA granted fast track designation to PDS0101 for use in combination with pembrolizumab in patients with recurrent or metastatic HPV16-positive head and neck cancer.³

References

1. Yoshida-Court K, Gjyishi O, Lin L, set al. IMMUNOCERV, an ongoing Phase II trial combining PDS0101, an HPV-specific T cell immunotherapy, with chemotherapy and radiation for treatment of locally advanced cervical cancers (NCT04580771). Presented at: 2022 SITC Annual Meeting; November 8-12, 2022; Boston, MA. Abstract 674
2. PDS Biotech announces 100% clinical response in cervical cancer patients in preliminary data from IMMUNOCERV phase 2 clinical trial. News release. PDS Biotech. November 14, 2022. Accessed November 16, 2022. https://bit.ly/3hLQh23
3. PDS Biotechnology granted FDA fast track designation for lead candidate PDS0101. News release. PDS Biotechnology Corporation. June 2, 2022. Accessed October 4, 2022. https://bit.ly/3mSq2WL