Synergy between Synthetic Long Peptides (SLP®) immunotherapeutics and standard chemotherapy in late stage cancer including meaningful survival improvements in SLP immune responders

Leiden, The Netherlands, 19 March 2020 — ISA Pharmaceuticals B.V., a clinical-stage immunotherapy company, announces publication of its phase 2, CervISA study in the peer-reviewed journal “Science Translational Medicine”. The paper titled ‘Strong vaccine responses during chemotherapy are associated with prolonged survival’ can be found here.

The CervISA study was an open label, phase 2 study in patients with late stage HPV16 positive cervical cancer. Seventy-seven patients were treated with ISA Pharma’s lead product, ISA101b, an HPV16-specific immunotherapeutic agent, in combination with standard-of-care (SoC) chemotherapy (carboplatin/paclitaxel). The addition of ISA101b to SoC chemotherapy led to a strong and highly specific anti-tumor immune response and significant improvement of patient survival in responding patients as evident from the following observations:

• + A strong correlation was seen between strength of the HPV-specific immune response and overall survival (OS). There was significantly longer (p=0.012) overal survival in patients with a good immune response (median OS 16.8 months) compared to patients with a weak response (median OS 11.2 months).

• + Additionally, 11 of the 14 patients still alive at the end of the study displayed a strong vaccine-induced response and included 9 FIGO stage IVa-IVb patients who had a mean OS of 3 years, an encouraging indication of highly durable survival outcomes in responding patients.

Professor Kees Melief, Chief Scientific Officer of ISA Pharmaceuticals, said: “We previously demonstrated that standard-of-care carboplatin/paclitaxel chemotherapy reduces abnormally high numbers of immunosuppressive myeloid cells, while leaving T-cell levels unharmed¹. Timed SLP therapy creates a highly specific T-cell mediated immune response, during the chemotherapy regimen. With this study, conducted in close collaboration with Prof. Sjoerd van der Burg and colleagues of the Leiden University Medical Center and the Oncode Institute, we have now convincingly confirmed the complementary benefit of these two treatment modalities without any additional toxicity burden. This type of chemo-immunotherapy approach may be generally applicable across many cancer types if the vaccine ingredients are changed to tumor-associated or neoantigen-containing SLP instead of HPV-SLP.”

Gerben Moolhuizen, Chief Executive Officer of ISA Pharmaceuticals, said: “This study provides valuable insights into how best to apply our immunotherapies in a late stage cancer clinical setting as well as in combination with standard-of-care chemotherapy. ISA Pharma is aiming to accelerate a number of novel SLP therapies into clinical development. We are happy to see such clear synergy between our SLPs and chemotherapy. A previous clinical study has also demonstrated a benefit of combining ISA101b with anti-PD1 therapy: a doubling of response rates and survival in Head and Neck cancer compared to the responses reported for anti-PD1 therapy alone². Our SLPs are thus expected to offer multiple options for advancing treatment of both pre-malignant and late stage cancers.”

References

1. 1. Welters MJ, et al. Sci Transl Med. 2016
2. 2. Massarelli E, et al. JAMA Oncology. 2018