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Patient either has one of the following histologically or cytologically confirmed advanced cancers not amenable to curative intent surgical resection |
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Advanced TNBC |
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SCCHN (oral cavity, oropharynx, hypopharynx, or larynx) |
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HGSOC including fallopian tube and primary peritoneal cancers |
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RCC. Or the patient has histologically or cytologically confirmed SCCHN scheduled to have curative intent surgical resection |
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Specific criteria for prior treatment of individual tumour types are as follows |
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TNBC |
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The patient has received available standard therapy for advanced disease (Modi-1/Modi-1v monotherapy cohorts only), or |
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Patients who stopped immunotherapy due to toxicity and with residual disease as measurable by RECIST 1.1 (Modi-1/Modi-1v monotherapy cohorts only), or |
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Patients completing a systemic treatment regimen with immunotherapy, for whom a subsequent standard of care therapy is not yet indicated or appropriate and with measurable disease in accordance with RECIST 1.1 (Modi-1/Modi-1v monotherapy cohorts only), or |
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Patients with residual disease as measurable by RECIST 1.1 on an ongoing standard of care immunotherapy regimen (Modi-1 + CPI combination cohorts only) |
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HPV (-) SCCHN |
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The patient should have received first-line platinum containing chemotherapy (with or without radiotherapy) as treatment for advanced disease (Modi-1/Modi-1v monotherapy cohorts and Modi 1 + CPI cohorts), or |
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Patients with locally advanced or metastatic disease as measurable by RECIST 1.1 for whom all forms of platinum-based chemoradiotherapy treatment are contraindicated (Modi-1/Modi-1v monotherapy cohorts and Modi 1 + CPI cohorts), or |
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Patients completing immunotherapy therapy for whom a subsequent standard of care therapy is not yet indicated or appropriate and with measurable disease in accordance with RECIST 1.1 (Modi-1/Modi-1v monotherapy cohorts only), or |
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Patients who stopped immunotherapy due to toxicity or completion of immunotherapy but with measurable disease in accordance with RECIST 1.1 (Modi-1/Modi-1v monotherapy cohorts only), or |
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For untreated metastatic or unresectable recurrent SCCHN in adults whose tumours express PD-L1 with a combined positive score (CPS) of one or more (Modi-1 + CPI cohorts only), or |
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Patients with residual disease as measurable by RECIST 1.1 on ongoing standard of care CPI monotherapy (Modi-1 + CPI combination cohorts only) |
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SCCHN |
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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 pembrolizumab) has been established |
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HGSOC including fallopian tube and primary peritoneal cancers |
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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 more than two non-platinum regimens (Modi-1/Modi-1v monotherapy cohorts), or |
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Patients completing a course of systemic therapy for whom a subsequent standard of care therapy is not yet indicated or appropriate and with measurable disease in accordance with RECIST 1.1 (Modi-1/Modi-1v monotherapy cohorts only) |
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RCC |
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The patient must have received first-line treatment consisting of anti-angiogenic |
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therapy. The patient must also have favourable or intermediate International |
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Metastatic Renal-Cell Carcinoma Database Consortium (IMDC) risk score (Heng et al |
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) (Modi1/Modi-1v monotherapy cohorts and Modi-1 + CPI cohorts), or |
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Patients who stopped immunotherapy due to toxicity and with residual disease as |
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measurable by RECIST 1.1 (Modi-1/Modi-1v monotherapy cohorts only), or |
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Patients completing immunotherapy, for whom a subsequent standard of care therapy |
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is not yet indicated or appropriate and with measurable disease in accordance |
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with RECIST 1.1 (Modi-1/Modi-1v monotherapy cohorts only), or |
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Patients on active surveillance (Modi-1/Modi-1v monotherapy cohorts only), or |
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Patients eligible for standard of care nivolumab immunotherapy (Modi-1 + CPI |
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combination cohorts only), or |
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Patients with residual disease as measurable by RECIST 1.1 on ongoing standard of |
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care monotherapy CPI (Modi-1 + CPI combination cohorts only) |
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Patient has completed their last dose of prior cancer therapy at least 4 weeks before |
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the first dose of study treatment |
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Patient has been fully vaccinated against COVID-19, the last vaccination being at |
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least 28 days prior to enrolment, except for those who have declined or are not |
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eligible for COVID-19 vaccination |
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Patient has recovered to Grade ≤1 (CTCAE v5.0) from the effects (excluding alopecia) |
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of any prior therapy for their malignancies |
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Patient has at least one measurable lesion per RECIST 1.1 criteria by computed |
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tomography scan or magnetic resonance imaging (non-neoadjuvant cohorts) |
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Wherever possible, patients not scheduled for curative intent resection surgery should |
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have a fresh tumour biopsy (or have an archival biopsy [obtained within the past 5 |
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years] if obtaining a fresh biopsy is not feasible) at baseline for molecular studies |
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and agree to a post-treatment biopsy (at Week 25 or the end of treatment visits), if |
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feasible. Patients in the SCCHN neoadjuvant cohort must have both a fresh |
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pre-treatment biopsy and agree to have their resected tumour analysed |
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Patient is male or female and at least 18 years of age |
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Patient has a life expectancy of more than 6 months |
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Patient has an ECOG performance status of 0 or 1 |
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Patient has adequate organ function as determined by the following laboratory values |
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Absolute neutrophil count ≥1.5 x 10^9/L |
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Platelet count ≥100 x 10^9/L |
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Haemoglobin >90 g/L (>5.6 mmol/L) |
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Lymphocytes ≥1 x 10^9/L |
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Serum creatinine ≤1.5 x the upper limit of normal (ULN) |
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Serum total bilirubin ≤1.5 x ULN (an exception for patients with Gilbert's |
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syndrome may be granted after discussion with the Sponsor) |
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Serum transaminases (aspartate transaminase/alanine transaminase) ≤2.5 x ULN or |
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≤5.0 x ULN if liver metastases are present |
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Patient must be able and willing to provide written informed consent prior to any |
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study related procedure. In the event that the patient is re-screened for study |
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participation or if a protocol amendment alters the care of an ongoing patient, a new |
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informed consent form must be signed |
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Women of child-bearing potential must have a negative serum pregnancy test during |
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Screening (and urine test within the 7 days prior to Day 1) and be neither |
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breastfeeding nor intending to become pregnant during study participation. Women of |
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child-bearing potential must agree to use highly effective contraceptive methods prior |
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to study entry, for the duration of study participation and for 120 days after |
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discontinuation of vaccine monotherapy or 5 months after use with a CPI (or longer if |
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the summary of product characteristics [SmPC] of the CPI requires it) |
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Men who are potentially fertile with partners of child-bearing potential must agree to |
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use highly effective contraceptive methods for the duration of study participation |
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and for 120 days after discontinuation of vaccine monotherapy or 5 months after use |
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with a CPI (or longer if the SmPC of the CPI requires it) |
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Patient must be willing and able to comply with scheduled visits, treatment plan |
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laboratory tests and other study procedures |
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Patients scheduled to receive a CPI (e.g., pembrolizumab or nivolumab) together with |
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Modi 1 must have been clinically evaluated, have not received prior CPI therapy, and |
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the CPI must be deemed an appropriate treatment for their disease according to the |
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CPI's SmPC |
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Patient has symptomatic central nervous system metastases or carcinomatous meningitis
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Patient is taking any systemic steroid therapy (exceeding 10 mg/day of prednisolone or
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equivalent) or is on any other form of immune suppressant medication within 2 weeks
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prior to the first dose of investigational study treatment. Physiological doses of
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systemic steroids such as those for the management of adrenal insufficiency, topical
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and inhaled steroids, such as those for the management of asthma, and patients with
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hypothyroidism stable on hormone replacement, are permitted
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Patient has a history of malignancy other than the disease under study within the 2
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years prior to Screening, with the exception of malignancies with a negligible risk of
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metastasis or death (e.g., with a 2-year overall survival rate >90%), such as
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adequately treated carcinoma-in-situ of the breast or the cervix, melanoma-in-situ
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non-melanoma skin carcinoma, superficial bladder cancer, prostate cancer with Gleason
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grade ≤6 and prostate specific antigen within normal range, or stage I endometrial
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cancer
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Patient is pregnant, lactating, or is expecting to conceive/father children within the
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duration of the study
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Patient has a concurrent illness which would preclude study conduct and assessment
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including, but not limited to, uncontrolled medical conditions, uncontrolled and
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active infection (considered opportunistic, life threatening, or clinically
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significant), uncontrolled risk of bleeding, uncontrolled diabetes mellitus, pulmonary
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disease (including obstructive pulmonary disease and pulmonary fibrosis), alcoholic
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liver disease, or primary biliary cirrhosis
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Patient has New York Heart Association class III or IV heart disease, has had a
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myocardial infarction or stroke within the previous 6 months prior to the Screening
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has a history of significant cardiac abnormality and/or significant abnormal baseline
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ECG readout, active ischaemia, or any other uncontrolled cardiac condition such as
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angina pectoris, clinically significant arrhythmia requiring therapy, uncontrolled
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hypertension, significant cerebrovascular disease, or congestive heart failure
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Patient has anti-citrullinated peptide antibody levels of ≥7 U/mL (classified as
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equivocal or positive according to NHS guidelines) or an active autoimmune disease
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that may impact on the study treatment in the opinion of the Investigator
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Patient has received a live vaccine or influenza vaccine within 28 days prior to the
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first dose of study treatment. The timing of any other vaccines should be assessed on
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a case-by-case basis by the Investigator prior to study enrolment
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Patient has a known history of human immunodeficiency virus (HIV) or has any positive
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test for hepatitis B virus (surface antigen reactive) or hepatitis C virus (RNA
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detected) indicating active acute or chronic infection
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COVID-19 vaccination within 28 days prior to the first dose of study treatment
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Patient has a known current or recent history (within the last year) of substance
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abuse including illicit drugs or alcohol
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