An open-label study in patients with advanced cancer

Phase 1

Conditions: Patients with metastatic/unresectable tumors of interest which include NSCLC, esophageal carcinoma, gastric carcinoma, HNSCC, urothelial carcinoma, ovarian carcinoma and synovial sarcoma
MedDRA version: 21.0Level: PTClassification code 10062006Term: HLA marker studySystem Organ Class: 10022891 - Investigations
MedDRA version: 21.0Level: PTClassification code 10030155Term: Oesophageal carcinomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 20.1Level: LLTClassification code 10017770Term: Gastric carcinomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 20.0Level: LLTClassification code 10064467Term: Urothelial carcinomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 21.1Level: LLTClassification code 10033131Term: Ovarian carcinomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 20.0Level: PTClassification code 10042863Term: Synovial sarcomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2018-003120-36-GB

Lead Sponsor: Immunocore Limited

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: 174

Inclusion Criteria

1. Age = 18 years at time of informed consent
2. Ability to understand and provide written informed consent prior to undergoing any study procedures
3. Life expectancy of at least 3 months as estimated by the Investigator
4. Eastern Cooperative Oncology Group (ECOG) status of 0 or 1 at start of treatment
5. HLA-A*02:01 positive (testing by central laboratory)
6. MAGE-A4-positive tumor , defined as follows:
a. Documentation of a histologically confirmed diagnosis of a tumor type in which MAGE-A4 expression is detectable in >70% of tumors (eg, serous ovarian carcinoma or synovial sarcoma). Note that the availability of an adequate tumor biopsy (as defined in the study Laboratory Manual) for retrospective MAGE-A4 testing must be confirmed during Screening
b. For tumor types in which MAGE-A4 expression is detectable in = 70% of tumors (eg, NSCLC, esophageal, gastric, HNSCC, or urothelial carcinoma) and tumor types for which the frequency of MAGE-A4 expression is unknown, tumor MAGE-A4 expression must be documented based on testing by the study central laboratory
7. Patients enrolling in biomarker backfill cohorts must have disease that is amenable to biopsy and consent to undergo biopsies during Screening and on treatment
8. Patients who are enrolling in Phase 1 may have either measurable or only non-measurable disease, and patients who are enrolling in Phase 2 must have measurable disease, according to RECIST v1.1
a. A previously irradiated lesion may be followed as a target lesion only if there was documented progression of the lesion following completion of radiotherapy
b. A lesion that will be biopsied on study may be followed as a target lesion only if it is > 2 cm in diameter and the biopsy will not significantly impact its diameter
9. Patients with metastatic/unresectable solid tumors are eligible. Patients must meet the indication-specific histology and biomarker testing requirements specified in the protocol
10. There is no maximum limit on the number of prior therapies. Patients must be relapsed from, refractory to, or intolerant of all therapies listed in the protocol for their indication and study phase. These therapies must have been given for unresectable / metastatic disease or given in the adjuvant setting if disease progression occurred during or within 6 months of completing adjuvant therapy
11. Male and female patients who are sexually active with a nonsterilized partner must agree to use highly effective methods of birth control from the trial screening date until 6 months after the final dose of the investigational product; cessation of birth control after this point should be discussed with a responsible physician. Highly effective methods of contraception are described in Section 6.4.4.
• Pregnant or lactating women are prohibited from enrolling
• Male patients are not allowed to donate sperm from the time of
enrolment until 6 months post-administration of study drugs

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 170
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 4

Exclusion Criteria

1. Presence of untreated or symptomatic central nervous system (CNS) metastases, leptomeningeal disease, or cord compression NOTE: patients with treated CNS lesions may enroll provided ALL the following apply:
• Treated CNS lesions must be radiographically stable for = 2 weeks after intervention (surgery and/or radiation)
• Patients must be neurologically stable and off systemic corticosteroids for = 2 weeks prior to the planned first dose of study treatment
2. Bowel obstruction within 3 months prior to the planned first dose of study treatment
3. Ongoing ascites or pleural effusion requiring recurrent paracentesis (ie, at least twice within 28 days prior to the planned first dose of study treatment)
4. Presence of NCI CTCAE = Grade 2 toxicity due to prior cancer therapy (excepting Grade 2 alopecia, Grade 2 stable peripheral neuropathy, Grade 2 endocrine disorder [on stable replacement doses], Grade 2 hypophosphatemia [on appropriate replacement therapy], and Grade 2 ototoxicity)
5. Patients enrolling in Arm A2 or Arm B2 with prior immunotherapy exposure must not have experienced immune-mediated AE (imAE) meeting any of the following criteria:
• Grade 4 imAE
• imAE resulting in the discontinuation of any prior single-agent immunotherapy
•imAE that did not resolve with initial immunosuppressive intervention (eg, corticosteroids, infliximab, mycophenolate mofetil)
• imAE that recurred upon rechallenge
• Any neurological or ocular imAE
• Pneumonitis that required oral or IV steroids
6. Receipt of anti-cancer therapy for the disease under study within the following times prior to the first planned dose of study drug:
• Cellular therapies (eg, CAR-T): 90 days. Please refer to the NOTE added in the clinical study protocol for this exclusion criteria.
• CTLA-4 targeted immunotherapies (eg, ipilimumab):28 days
• HER2-targeted antibodies (eg, trastuzumab):28 days
•All other immunotherapies (eg, atezolizumab, pembrolizumab): 21 days
• All other systemic therapies: 14 days
• Radiotherapy: 14 days (excepting palliative radiotherapy to a limited field, which is permitted at any time)
7. Patient with an out-of-range Screening laboratory values defined as shown below
• Creatinine clearance (calculated using Cockcroft-Gault formula, or measured) < 40 mL/min
• Total bilirubin > 1.5 × ULN (patients with Gilbert's syndrome are excluded if total bilirubin > 3.0 x ULN or direct bilirubin > 1.5 × ULN)
• ALT > 3 × ULN
• AST > 3 × ULN
• Absolute neutrophil count < 1.0 × 109/L
• Absolute lymphocyte count < 0.5 × 109/L
• Platelet count < 75 × 109/L
• Hemoglobin < 8 g/dL
8. Evidence of active pneumonitis at Screening by chest imaging or the
ongoing requirement for intermittent or continuous supplemental
oxygen
9. Clinically significant cardiac disease or impaired cardiac function,
including any of the following:
• Uncontrolled hypertension (consistent findings of systolic blood
pressure [BP] > 160 mmHg or diastolic BP > 110 mmHg as defined in
the protocol
•History of ventricular arrhythmia currently requiring medical treatment
or uncontrolled atrial fibrillation
• Ejection fraction < 50% on Screening echocardiogram
• QTcF > 470 msec on Screening ECGs or known history of congenital
prolonged QT syndrome
• Cardiac troponin T > ULN at Screening
• Acute myocardial infarction or unstable angina pectoris = 6 months
prior to Screening
10. Active autoimmune disease requiring treatment, including
inflammatory bowel disease (ulcerative colitis or Crohn's disease),
within

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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