ModiFY (Modi-1 Scancell)

1) Patient has one of the following advanced cancers not amenable to curative intent surgical resection:

Advanced TNBC, SCCHN (oral cavity, oropharynx, hypopharynx, or larynx), High grade serous ovarian carcinoma including fallopian tube and primary peritoneal cancers (PPCs) or RCC.

Or the patient has confirmed SCCHN scheduled to have curative intent surgical resection.

2) Criteria for prior treatment are:

TNBC; patient has received available standard therapy (without immunotherapy) for advanced disease, and is eligible for immunotherapy alone.

SCCHN; patient should have received first-line platinum-containing chemotherapy (with or without radiotherapy) as treatment for advanced disease. Patients with locally advanced disease for whom all forms of platinum-based chemoradiotherapy treatment are contraindicated, and who have an ECOG score of 0, must have received first-line cetuximab with radiotherapy unless they are not eligible to do so.

SCCHN (neoadjuvant expansion cohort only); patients who are treatment-naïve and are scheduled to have tumour resection surgery, in whom a period of 6 weeks of neoadjuvant immunotherapy can be administered. Patients will only be enrolled once the Modi-1 expansion doses and a lack of increased anti-CCP antibodies (with, and without, concomitant CPI [e.g. pembrolizumab or nivolumab]) has been established.

High grade serous ovarian carcinoma including fallopian tube and PPCs; the patient must be considered unsuitable for platinum chemotherapy, defined as recurrence/progression within 6 months of prior platinum-containing chemotherapy or patients in whom platinum therapy is no longer thought appropriate. Patients must have received no > than two non-platinum regimens.

RCC; the patient must have received first-line treatment consisting of anti-angiogenic therapy The patient must also have favourable or intermediate International Metastatic Renal-Cell Carcinoma Database Consortium (IMDC) risk score.

3) Patient has completed last dose of prior cancer therapy at 4 weeks before first dose of study treatment.

4) Patient has been fully vaccinated against COVID-19, the last vaccination being ≥ 28 days prior to enrolment, except for those who have declined or are not eligible.

5) Patient has recovered to Grade ≤ 1 (CTCAE v5.0) from the effects (excluding alopecia) of prior therapy for their malignancies.

6) Patient has ≥ 1 measurable disease lesion per RECIST 1.1 criteria by CT scan or MRI (non-neoadjuvant cohorts).

7) Wherever possible, patients not scheduled for curative intent resection surgery should have a fresh tumour biopsy (or an archival biopsy [obtained within the past 5 years] if obtaining a fresh biopsy is not feasible) at baseline for molecular studies, and agree to a post-treatment biopsy (at Week 25 or the EOT visit), if feasible. Patients in the SCCHN neoadjuvant cohort must have both a fresh pre-treatment biopsy and agree to have their resected tumour analysed.

8) Male or female at least 18 years of age.

9) Life expectancy of > than 6 months.

10) ECOG performance status of 0 or 1.

11) Adequate organ function as determined by the following laboratory values: absolute neutrophil count ≥ 1.5 x 10^9/L, platelets ≥ 100 x 10^9/L, haemoglobin > 90 g/L (> 5.6 mmol/L), lymphocytes ≥ 1 x 10^9/L, serum creatinine ≤ 1.5 x upper limit of the normal range(ULN), serum total bilirubin ≤ 1.5 x ULN (an exception for patients with Gilbert’s syndrome may be granted after discussion with the Sponsor), serum transaminases (aspartate aminotransferase[AST]/alanine aminotransferase[ALT]) ≤ 2.5 x ULN or ≤ 5.0 x ULN if liver metastases present.

12) Able and willing to provide written informed consent prior to any study procedure.

13) Women of child-bearing potential must have a negative serum pregnancy test during screening (and a urine test within the 7 days prior to Day 1) and be neither breastfeeding nor intending to become pregnant during the study. They must agree to use highly effective contraceptive methods prior to and during the study and 120 days after discontinuation of study treatment.

14) Men who are potentially fertile with partners of childbearing potential must agree to use highly effective contraceptive methods for the duration of the study and for 120 days after discontinuation of study treatment.

15) Must be willing and able to comply with study visits, procedures and treatment plan.

16) Patients scheduled to receive CPI (e.g. pembrolizumab or nivolumab) together with Modi-1 must be clinically evaluated, have not received prior CPI therapy and the CPI must be deemed an appropriate treatment for their disease according to the CPI's SmPC. 

1) Patient has symptomatic central nervous system metastases or carcinomatous meningitis.

2) 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.

3) Patient has a history of malignancy other than the disease under study within the 2 years prior to Screening, with the exception of malignancies with a negligible risk of metastasis or death (e.g., with a 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.

4) Patient is pregnant, lactating, or is expecting to conceive/father children within the duration of the study.

5) Patient has a concurrent illness which would preclude study conduct and assessment, including, but not limited to, uncontrolled medical conditions, uncontrolled and active infection (considered opportunistic, life threatening, or clinically significant), uncontrolled risk of bleeding, uncontrolled diabetes mellitus, pulmonary disease (including obstructive pulmonary disease and pulmonary fibrosis), alcoholic liver disease, or primary biliary cirrhosis.

6) Patient has NYHA class III or IV heart disease, has had a myocardial infarction or stroke within the previous 6 months prior to the Screening, has a history of significant cardiac abnormality and/or significant abnormal baseline ECG readout, active ischaemia, or any other uncontrolled cardiac condition such as angina pectoris, clinically significant arrhythmia requiring therapy, uncontrolled hypertension, significant cerebrovascular disease, or congestive heart failure.

7) Patient has anti-CCP antibody levels of ≥ 7 U/mL (classified as equivocal or positive according to NHS guidelines) or an active autoimmune disease that may impact on the study treatment in the opinion of the Investigator.

8) Patient has received a live vaccine or influenza vaccine within 28 days prior to the first dose of study treatment. The timing of any other vaccines should be assessed on a case-by-case basis by the Investigator prior to study enrolment.

9) Patient has a known history of HIV or has any positive test for HBV (surface antigen reactive) or HCV (RNA detected) indicating active acute or chronic infection.

10) COVID-19 vaccination within 28 days prior to the first dose of study treatment.

11) Patient has a known current or recent history (within the last year) of substance abuse including illicit drugs or alcohol. 

Research Nurse: Lizzie Coates (x2031) Elizabeth.Coates@LTHTR.nhs.uk