Results from promising trials in the fight against head and neck cancer have been presented at the American Society of Clinical Oncology (ASCO) annual meeting in Chicago.
Transgene, a biotech company that designs and develops virus-based immunotherapies for the treatment of cancer, and NEC Corporation, a provider of IT, network and AI technologies, announced new data on TG4050, an individualized neoantigen cancer vaccine, while ISA Pharmaceuticals B.V., a clinical-stage biotechnology company developing immunotherapies to treat cancers and serious infectious diseases, presented the first clinical data of the combination of ISA101b (peltopepimut-S) and Regeneron’s anti-PD-1 Libtayo (cemiplimab).
Cue Biopharma Inc. also presents positive data from its ongoing phase 1 trials of CUE-101 for recurrent/metastatic HPV+ head and neck squamous cell carcinoma at the ASCO meeting.
Transgene’s positive data
The new positive data from Transgene have been generated from patients with HPV-negative head and neck cancer who have been enrolled in an ongoing randomized phase I trial assessing TG4050. All patients treated with TG4050 in the trial have developed a specific immune response, as demonstrated by the results of additional immunological testing, and remained disease-free to date.
Alessandro Riva, chairman and CEO of Transgene, said: “TG4050 is showing its potential to extend patient remission after surgery and firmly establishes Transgene among the leading pioneers in the emerging field of individualized cancer vaccines. The monotherapy data we are presenting at ASCO are a solid basis to accelerate the clinical development of this innovative therapy as an adjuvant treatment to HPV-negative head and neck carcinoma and potentially in other indications.”
Masamitsu Kitase, corporate senior VP, head of healthcare and Life Science Division, NEC Corporation, added: “We are excited by the additional data from immunological testing that is being presented in the poster at ASCO. It is certainly an encouraging outcome for NEC’s AI prediction for neoantigens that are able to effectuate an immunological response. These are early results that underpin NEC’s AI capability of making predictions that help in making TG4050 an efficacious product for patients across the globe. We look forward to working with Transgene to develop on this asset further.”
Strong immune responses after treatment with Transgene’s TG4050
The data presented at ASCO 2023 show that all evaluable patients developed a specific immune response after treatment with TG4050 against multiple cancer neoantigens. These immune responses were developed in spite of patients having unfavorable systemic immunity and tumor micro-environment at baseline (with the presence of non-functional immune cells or with low or negative levels of PD-L1 expression). These challenging characteristics are normally associated with limited responses to treatments, including immune checkpoint blockers.
Two patient case studies are also being reported. In these patients who are disease-free following treatment with TG4050, immunoreactive T cell response against targeted antigens was assessed by tetramer staining. The results confirm a large amplification of the frequency of immunoreactive T cells. These T cells were characterized as effector cytotoxic T cells, a cell population with potential anti-tumor activity. These data further demonstrate that TG4050 is able to induce an anti-tumor cellular immune response.
All patients in the trial who received TG4050 remain disease-free to date.
As of May 2023, 32 patients were randomized in the head and neck cancer phase I trial. All 16 patients who received TG4050 remained disease-free, with a median follow-up time of 10.4 months. This compares favorably to the control arm, in which two patients with similar characteristics experienced relapse. Two other patients also showed biochemical signs of relapse, as seen in the poster. These patients are still being followed in the ongoing trial.
To date, the vaccine has been well tolerated and no related serious adverse events have been reported.
The last patient has recently been randomized in the head and neck cancer trial. Transgene and NEC plan to achieve a median follow up of 18 months in mid-2024.
The companies are preparing for a phase II trial in head and neck cancer, in an adjuvant setting, which could be initiated in H2 2023.
Last month, Transgene and BioInvent International AB announced positive phase Ia data on the oncolytic virus BT-001 for the treatment of solid tumors.
Promising results from ISA Pharmaceuticals’ ISA101b and Libtayo combo
Early data from the ISA Pharmaceuticals trial were presented, regarding 26 patients with recurrent and/or metastatic human papilloma virus type 16 (HPV16) positive oropharyngeal cancer (OPC, a form of head and neck cancer) who progressed on pembrolizumab or nivolumab, and were followed for at least six months.
This population included patients that have never responded to prior anti-PD1 therapy. Patients were treated until disease progression, toxicity, treatment withdrawal for up to 24 months. Recruitment in this study is ongoing.
The combination of ISA101b and cemiplimab in these patients resulted in an overall response rate of 15.4%, as per investigator assessment. Long term (≥6 months) disease stabilization was achieved in 26.9% of all patients. The combination of cemiplimab and ISA101b was generally well tolerated with a safety profile resembling that of anti-PD-1 monotherapy.
There were two grade 3 adverse events related to ISA101b. Grade 4-5 events related to study treatment did not occur. Re-ignition of an anti-tumor effect of anti-PD-1 therapy after failure of checkpoint inhibition by the addition of a therapeutic vaccine is a unique feature.
Anthony Kong, principal investigator and medical oncologist at King’s College in London, said: “The initial results of this study are promising, given the high unmet medical need in this difficult-to-treat patient population.”
Leon Hooftman, chief medical officer of ISA Pharmaceuticals, said: “The most impressive element of this data-set of anti-PD1 therapy-resistant head and neck cancer patients is the 6 months’ disease control rate: it appears that the targeted therapeutic cancer vaccine ISA101b together with an anti-PD1 antibody can have a real stabilizing effect in a fair proportion of these sick patients.”
In September 2021, ISA101b was granted Fast Track designation by the U.S. Food and Drug Administration (FDA) for the treatment of recurrent and metastatic HPV16 positive OPC.
Cue Biopharma data
Cue Biopharma’s presentation was an update of its ongoing phase 1 clinical trials evaluating its lead biologic from the IL-2-based CUE-100 series, CUE-101, for the treatment of patients with human papilloma virus (HPV16+) recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) as a monotherapy and in combination with pembrolizumab.
“CUE-101 clinical data to date continues to demonstrate both promising evidence of single-agent activity as well as complementary activity in combination with checkpoint inhibitor pembrolizumab,” said Matteo Levisetti, chief medical officer of Cue Biopharma.
“Based on the strength of the data to date, we believe CUE-101 has the promise to be a potential therapeutic advancement for patients battling head and neck cancer, a devastating disease of unmet medical need, with potential registrational paths both as monotherapy and in combination with pembrolizumab.”
Key data highlights include an overall response rate of around 40% with 4 out of 5 confirmed PRs occurring in tumors with low PD-L1 expression as evidenced by combined positive scores of 20 or less. All 5 patients with a confirmed partial response demonstrated more than 99% reduction in circulating cell-free HPV DNA (HPV cfDNA).
The median duration of response is 35 weeks with a median progression free survival approaching 5 months.
Dan Passeri, chief executive officer of Cue Biopharma, said: “Overall, the emerging data supports the potential of CUE-101 to provide patients with an enhanced disease control rate. We look forward to continuing to evaluate responses in these patients in addition to assessing the registrational trial options for CUE-101.
“Furthermore, the observed evidence of single agent activity in late-stage patients and the complementary mechanism of action in combination with checkpoint inhibition holds the potential to enhance anti-tumor activity across a broad range of cancers with our Immuno-STAT platform.”
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