by Charlotte Kilpatrick | Sep 16, 2024 | Therapeutic |
In September 2024, IO Biotech announced “promising” data from its Phase II basket trial of IO102-IO103 in combination with Merck’s anti-PD-1 therapy KEYTRUDA (pembrolizumab). These results were shared in a conference presentation that included clinical and biomarker data from patients with recurrent or metastatic (advanced) squamous cell carcinoma of the head and neck (SCCHN) with PD-L1 CPS ≥ 20. The study met its primary endpoint and identified a safety profile consistent with prior studies.
IO102-IO103
IO Biotech’s lead product candidate is IO102-IO103, which combines two wholly owned T-win vaccines designed to “activate and expand” T cells specific for IDO and PD-L1. T-win is an immune-modulating vaccine technology that is directed against tumour cells and the “most important” immune-suppressive cells in the tumour microenvironment (TME). Many types of solid tumours and immune-suppressive cells (Tregs and TAms) in the TME overexpress IDO and/or PD-L1. Thus, the combination of the two vaccines is intended to “have a synergistic effect” that leads to “enhanced cell killing”.
The Phase II basket study is a non-comparative, open-label trial that investigates the safety and efficacy of a combination of IO101-IO103 with pembrolizumab as a first-line treatment in up to 60 patients with metastatic non-small cell lung cancer (NSCLC) with PD-L1 TPS ≥ 50% and recurrent or metastatic SCCHN with PD-L1 CPS ≥ 20. The primary endpoint is overall response rate (ORR).
Promising data
Data from 18 efficacy evaluable patients revealed:
- The achievement of the primary endpoint – confirmed 44.4% overall response rate (ORR) in a PD-L1 high population of patients with SCCHN irrespective of HPV status.
- An “encouraging” 6.6-month median progression-free survival (PFS).
- A 66.7% disease control rate (DCR).
- A safety profile that is consistent with previously reported data from a combination approach.
- The detection of T-cell responses to both IO102 (targeting IDO) and IO103 (targeting PD-L1) after treatment.
Dr Jonathan Riess, principal investigator of the trial and Director, Thoracic Oncology at UC Davis Comprehensive Cancer Centre, is encouraged by the data in support of the combination approach.
“Given the need for new treatment options that are effective, safe, and accessible for head and neck cancer patients, further investigation of this combination should be conducted to build on the findings of this Phase II trial.”
Chief Medical Officer of IO Biotech, Dr Qasim Ahmad described “accumulating” evidence that the combination could be a “safe and efficacious first-line treatment for patients with a range of cancers”. This includes those with metastatic and “difficult-to-treat disease”.
“Importantly, with mPFS of 6.6 months, more than half of the patients in this trial had over 180 days of progression-free survival. These data are supportive of further investigation of this combination regimen as part of our commitment to transform the lives of cancer patients through our novel therapeutic vaccine.”
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by Charlotte Kilpatrick | Aug 6, 2024 | Therapeutic |
In August 2024 Ultimovacs announced topline data from the FOCUS Phase II trial combining UV1 and pembrolizumab in patients with metastatic or recurrent head and neck squamous cell carcinoma, revealing that the combination did not meet primary or secondary endpoints. Although the vaccine “continues to show a positive safety profile”, adding it to the standard of care did not lead to clinical benefits in progression free survival or overall survival in late-stage HNSCC patients. Head and neck cancer is the seventh most common type of cancer globally, with squamous cell carcinoma representing about 90% of those patients.
“Despite advances in treatment strategies, the prognosis for these patients is poor.”
UV1
UV1 is Ultimovacs’ therapeutic cancer vaccine, designed to induce a specific T cell response against telomerase. It comprises long, synthetic peptides representing a sequence in the reverse transcriptase subunit of telomerase (hTERT), which is shown to induce CD4+ T cells. After intradermal injection, antigen presenting cells (APCs) in the skin are exposed to vaccine peptides. The APCs process the peptides and present vaccine epitopes on Human Leukocyte Antigen (HLA) molecules to naïve T cells in the lymph nodes.
FOCUS
The trial is an investigator-initiated randomised Phase II clinical trial, sponsored by Martin-Luther-University Halle-Wittenberg with support from Ultimovacs, taking place across 10 sites in Germany. It investigates Ultimovacs’ therapeutic cancer vaccine, UV1, in combination with pembrolizumab, compared to pembrolizumab alone, as a first-line treatment in patients with recurrent PD-L1 positive head and neck squamous cell carcinoma (HNSCC). The primary endpoint is progression free survival at 6 months.
A disappointing result
Dr Carlos de Sousa, Chief Executive Officer at Ultimovacs, reflected that the cancer vaccine has been tested in a “range of different indications” through a “broad Phase II clinical development programme”.
“Unfortunately, the FOCUS study did not provide us with the results we had hoped for, and we are disappointed that UV1 was not able to provide added clinical benefit for these HNSCC patients.”
Dr de Sousa stated that a cash preservation programme, implemented earlier in the year, enabled the team to “extend our runway” to the fourth quarter of 2025, beyond the anticipated DOVACC Phase II topline readout.
“Further, the Ultimovacs team is actively developing a novel technology platform identified during the TET development and we look forward to providing more details before year-end.”
Dr Jens Bjørheim, Ultimovacs’ Chief Medical Officer, echoed Dr de Sousa’s disappointment that the FOCUS trial “did not achieve the desired outcome for patients”, adding that this “underscores the complexities of treating metastatic and recurrent head and neck cancer”.
“This cancer type is particularly aggressive with limited treatment options and high rates of recurrence. Our broad clinical development programme was designed to identify the best patient populations for UV1 and we are now focusing our efforts on the upcoming DOVACC data readout in the first half of next year.”
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by Charlotte Kilpatrick | Jun 3, 2024 | Therapeutic |
Transgene announced in June 2024 that the first patient has been enrolled in the Phase II part of a randomised Phase I/II clinical trial of TG4050 in the adjuvant treatment of head and neck cancer. Patient screening and enrolment are underway, with hopes of enrolling 80 patients internationally to continue the trial after Phase I data showed immunogenicity and first signs of clinical benefit. TG4050 is based on Transgene’s myvac viral vector platform and NEC’s cutting-edge AI capabilities for the identification and prediction of the most immunogenic neoantigens for every patient.
“TG4050 is the only individualised neoantigen cancer vaccine currently being developed in a randomised trial in the adjuvant treatment of head and neck cancer.”
The vaccine shows promise
Transgene states that “promising” data from Phase I showed “strong immunogenicity” and a “persistent cellular immune response” as well as “signs for clinical benefit for patients”. At the time of analysis all patients who received TG4050 were disease-free. Therefore, Transgene and partner NEC are moving into an extension of the randomised trial.
The Phase II will continue investigating single-agent TG4050 in patients with newly diagnosed, locoregionally advanced, HPV-negative, squamous cell carcinoma of the head and neck (SCCHN) in the adjuvant setting following completion of surgery and chemoradiotherapy. The international, multicentre, open label, two-arm trial is screening patients in Toulouse and Paris, in France, with other sites to be added in Europe and the US in the coming months.
A significant medical need
Despite advancements in the treatment of SCCHN, Transgene identifies a “significant medical need” for patients, including in the adjuvant setting. With the current standard of care, 30% to 40% of patients are expected to relapse within 24 months after surgery and adjuvant therapy. Dr Maud Brandely, Chief Medical Officer of Transgene, described the inclusion of the first patient as a “further milestone” for the company.
“In the ongoing trial, TG4050 is targeting patients with head and neck cancer at high-risk of relapse, with the aim of extending disease-free survival. The Phase I data we have generated indicate that TG4050 enables the induction of specific cellular immune responses that persist up to 7 months post treatment initiation, with all treated patients remaining disease-free after a median follow-up of 18.6 months.”
Dr Brandely is “encouraged” by the “promising clinical outcomes” and looks forward to generating more data.
“Personalised cancer vaccines are an extremely exciting development and, if successful, could also be utilised to treat other forms of cancer to improve and extend the lives of patients.”
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by Charlotte Kilpatrick | Mar 5, 2024 | Therapeutic |
In March 2024 Transgene, NEC Corporation, and BostonGene Corporation announced the expansion of their collaboration for the randomised Phase I/II trial of TG4050. TG4050 is an investigational cancer therapy vaccine, individualised for patients with head and neck cancers. It is based on Transgene’s myvac platform and is powered by NEC’s AI-driven Neoantigen Prediction System. The partnership will continue to perform tumour molecular profiling and microenvironment analysis, providing high-throughput sequencing services.
TG4050
TG4050 is a virus-based individualised immunotherapy that encodes neoantigens identified and selected by the Neoantigen Prediction System. It is designed to “stimulate the immune system” to induce a T-cell response that can “recognise and destroy tumour cells based on their own neoantigens”.
Comments on the collaboration
Dr Alessandro Riva, Chair and CEO of Transgene, is pleased to continue the collaboration, which has provided “in-depth information on patient phenotypes in the Phase I trial”.
“It has allowed us to understand the baseline status of our patients and how the tumour micro-environment (TME) might evolve following treatment.”
Masamitsu Kitase, Corporate SVP and Head of the Healthcare and Life Sciences Division at NEC Corporation, commented on the “combined expertise” of the partnership, which will “continue to provide a streamlined pipeline”. This will ensure “timely delivery of patient-tailored vaccines” alongside “data to guide the future development of new personalised treatment options” with the goal of “elevating the standard of care for head and neck cancer patients”.
BostonGene’s Chief Medical Officer Dr Nathan Fowler is “committed to supporting Transgene and NEC as they advance these clinical trials”.
“Our molecular and immune profiling techniques comprehensively analyse the tumour, microenvironment, and immune system to identify key predictors of response to TG4050, ultimately improving treatment outcomes.”
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