The main objectives of this study are to assess the safety, tolerability, immunological activity, and preliminary efficacy of the Modi-1 Moditope vaccine, both as monotherapy and in combination with a checkpoint inhibitor (CPI) such as pembrolizumab or nivolumab with or without Ipilimumab (where these are standard of care in a non-neoadjuvant setting), in patients with advanced triple negative breast cancer (TNBC), advanced/unresectable human papillomavirus-negative squamous cell carcinoma of the head and neck (SCCHN), high grade serous ovarian carcinoma (HGSOC), or renal cell carcinoma (RCC).
Modi-1 Moditope will also be investigated in the neoadjuvant setting for patients with SCCHN undergoing curative intent surgical resection in combination with pembrolizumab versus the Modi-1 alone.
TNBC
SCCHN (oral cavity, oropharynx, hypopharynx, or larynx)
HGSOC including fallopian tube and primary peritoneal cancers
RCC Or the patient has histologically or cytologically confirmed SCCHN scheduled to have curative intent surgical resection.
Patient has symptomatic central nervous system metastases or carcinomatous meningitis.
Patient is taking any systemic steroid therapy (exceeding 10 mg/day of prednisolone or equivalent) or is on any other form of immune suppressant medication within 2 weeks prior to the first dose of IMP. Physiological doses of systemic steroids such as those for the management of adrenal insufficiency, topical and inhaled steroids, such as those for the management of asthma, and patients with hypothyroidism stable on hormone replacement, are permitted.
Patient has a history of malignancy other than the disease under study within 2 years prior to Screening, with the exception of malignancies with a negligible risk of metastasis or death (e.g., 2-year overall survival rate >90%), such as adequately treated carcinoma-in-situ of the breast or the cervix, melanoma-in-situ, non-melanoma skin carcinoma, superficial bladder cancer, prostate cancer with Gleason grade ≤6 and prostate specific antigen within normal range or stage I endometrial cancer.
Patient is pregnant, lactating, or is expecting to conceive/father children within the duration of the study.
Parallel
Modi-1 Moditope
Biological/VaccineModi-1 Moditope administered intradermally (i.d.) using the MicronJet600™ microneedle device (NanoPass).
Pembrolizumab
Biological/VaccinePembrolizumab (exploratory cohorts) will be administered by intravenous infusion on Day 8, prior to tumour resection surgery at 6 weeks.
MicronJet600™ microneedle device (NanoPass)
DeviceIntradermal injection device
Incidence of clinical and laboratory adverse events (AEs)
To measure the incidence of AEs of Modi-1 Moditope (as monotherapy and in combination with a CPI (e.g., pembrolizumab or nivolumab provided as standard of care) when administered intradermally
Cellular immune response to Modi-1 Moditope on IFNγ ELISpot assay
(i) the mean peptide-specific ELISpot response minus two standard deviations is greater than the mean pre-treatment peptide-specific response plus one standard deviation (of this mean); and (ii) the ELISpot response is more than 50 spots per million peripheral blood mononuclear cells.
Imaging Response using RECIST 1.1 and iRECIST to Modi-1 Moditope in the non-neoadjuvant setting
To measure imaging response of Modi-1 Moditope in non-neoadjuvant cohorts, as monotherapy in patients with TNBC, advanced/unresectable HPV-negative SCCHN, HGSOC, or RCC and in combination with CPI therapy (e.g., pembrolizumab, nivolumab, Ipilimumab)
Overall survival
The overall survival will measured in patients vaccinated with Modi-1 Moditope either as monotherapy or in combination with checkpoint inhibitors in the target population.
Progression-free survival in patients vaccinated with Modi-1 Moditope
The progression-free survival will measured in patients vaccinated with Modi-1 Moditope either as monotherapy or in combination with checkpoint inhibitors in the target population.
Pathological response in the neoadjuvant setting in patients vaccinated with Modi-1 Moditope or Modi-1 Moditope + Pembrolizumab
Pathological response will be measured in tumour tissue of patients vaccinated with Modi-1 Moditope monotherapy or Modi-1 Moditope + Pembrolizumab in patients with SCCHN undergoing planned resection
Immune cell profiling in tumour samples
Immune cells will be profiled from available biopsy tissue
Measurement of circulating tumour deoxyribonucleic acid (ctDNA)
ctDNA will be measured in blood in patients vaccinated with Modi-1 Moditope either as monotherapy or in combination with checkpoint inhibitors in the target population.
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