Results from a promising trial 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 biotechnology company designing and developing virus-based immunotherapies for the treatment of cancer, and NEC Corporation, a provider of IT, networking and AI technologies, announced new data on TG4050, an individualized neoantigen cancer vaccine, while ISA Pharmaceuticals BV, a clinical-stage biotechnology company developing immunotherapy to treat cancer and serious infectious diseases, presented the first clinical data of the combination ISA101b (peltopepimut-S) and anti-PD-1 Libtayo (cemiplimab) Regeneron.
Cue Biopharma Inc. also presented positive data from the ongoing phase 1 trial of CUE-101 for recurrent/metastatic HPV+ head and neck squamous cell carcinoma at the ASCO meeting.
Transgene positive data
New positive data from Transgene have been generated from patients with HPV-negative head and neck cancer who have been enrolled in a continuous randomized phase I trial assessing TG4050. All patients treated with TG4050 in the trial developed a specific immune response, as indicated by the results of additional immunological tests, and have remained disease free to date.
Alessandro Riva, chairman and CEO of Transgene, said: “TG4050 demonstrates 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 present at ASCO is a strong basis for accelerating clinical development of this innovative therapy as an adjunctive treatment for HPV-negative head and neck carcinoma and potentially for other indications.”
Masamitsu Kitase, Corporate Senior VP, Head of Healthcare and Life Science Division, NEC Corporation, added: “We are very pleased with the additional data from immunology testing presented in the poster at ASCO. This is certainly an encouraging result for the prediction of AI NEC for neoantigens capable of generating an immunological response. These are early results supporting NEC’s AI ability to make predictions that help make the TG4050 a efficacy product for patients worldwide. We look forward to working with Transgene to further develop this asset.”
Strong immune response after treatment with Transgene’s TG4050
Data presented at ASCO 2023 demonstrated that all evaluated patients developed specific immune responses after treatment with TG4050 against several cancer neoantigens. This immune response developed despite the patient having systemic immunity and an unfavorable tumor microenvironment at baseline (in the presence of non-functional immune cells or with low or negative levels of PD-L1 expression). This challenging characteristic is usually associated with a limited response to treatments, including immune checkpoint inhibitors.
Two patient case studies are also being reported. In patients free of disease after treatment with TG4050, the response of immunoreactive T cells to the target antigen was assessed by tetramer staining. The results confirm a large amplification of the frequency of immunoreactive T cells. These T cells are characterized as effector cytotoxic T cells, a cell population with potential anti-tumor activity. These data further indicate that TG4050 is capable of inducing anti-tumor cellular immune responses.
Disease free status
All patients in the trial who received TG4050 have remained disease free to date.
In May 2023, 32 patients were randomized into a phase I trial of head and neck cancer. All 16 patients who received TG4050 remained disease free, with a median follow-up time of 10.4 months. This compares favorably with the control group, 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 ongoing trials.
To date, the vaccine has been well tolerated and no associated serious side effects have been reported.
The last patient was recently randomized into a head and neck cancer trial. Transgene and NEC plan to achieve an average follow-up of 18 months by mid-2024.
The company is preparing for a phase II trial in head and neck cancer, in additional settings, which could start in H2 2023.
Last month, Transgene and BioInvent International AB announced positive phase Ia data on oncolytic virus BT-001 for the treatment of solid tumors.
Promising results from the ISA101b and Libtayo combo from ISA Pharmaceuticals
Preliminary data from the ISA Pharmaceuticals trial are presented, regarding 26 patients with recurrent and/or metastatic human papilloma virus type 16 (HPV16) positive for oropharyngeal cancer (OPC, a form of head and neck cancer) who were continued on pembrolizumab or nivolumab, and were followed for at least six months.
This population includes patients who have never responded to previous anti-PD1 therapy. Patients are treated until disease progression, toxicity, discontinuation of treatment 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%, according to the investigators’ assessment. Long-term (≥6 months) disease stabilization was achieved in 26.9% of all patients. The combination of cemiplimab and ISA101b is generally well tolerated with a safety profile similar to that of anti-PD-1 monotherapy.
There are two grade 3 side effects associated with ISA101b. Class 4–5 events related to study treatment did not occur. Re-enactment of the 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 head and neck cancer patients resistant to anti-PD1 therapy is the rate of disease control over 6 months: it appears that the ISA101b vaccine targeted therapeutic cancer along with antibodies anti-PD1 can have a marked stabilizing effect in a large proportion of these ill patients.”
In September 2021, ISA101b was granted Fast Track designation by the US Food and Drug Administration (FDA) for the treatment of recurrent and metastatic HPV16 positive OPC.
Biopharma data cues
Cue Biopharma presentation is an update of an ongoing phase 1 clinical trial evaluating its biologic lead from the IL-2-based CUE-100 series, CUE-101, for the treatment of patients with recurrent/metastatic head human papilloma virus (HPV16+) and squamous cell carcinoma of the neck (R/M HNSCC) as monotherapy and in combination with pembrolizumab.
“CUE-101 clinical data to date continue to show promising evidence of single-agent activity as well as complementary activity in combination with the checkpoint inhibitor pembrolizumab,” said Matteo Levisetti, chief medical officer of Cue Biopharma.
“Based on the strength of data to date, we believe CUE-101 holds promise as a potential therapeutic advance for patients battling head and neck cancer, a terminal medically unmet disease, with a potential enrollment pathway as either monotherapy or in combination with pembrolizumab.”
Key data highlights include an overall response rate of approximately 40% with 4 of 5 confirmed PRs occurring in tumors with low PD-L1 expression as evidenced by a combined positive score of 20 or less. All 5 patients with confirmed partial response showed more than 99% reduction in circulating cell-free HPV DNA (HPV cfDNA).
The median duration of response was 35 weeks with a median progression-free survival of close to 5 months.
Dan Passeri, chief executive of Cue Biopharma, said: “Overall, the emerging data supports the potential for CUE-101 to provide patients with enhanced levels of disease control. We look forward to continuing to evaluate response in these patients in addition to assessing enrollment trial options for CUE-101.
“In addition, observed evidence of single agent activity in end-stage patients and complementary mechanisms of action in combination with checkpoint inhibition has the potential to enhance anti-tumor activity in multiple cancer types with our Immuno-STAT platform.”