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: 21.0 Level: PT Classification code 10062006 Term: HLA marker study System Organ Class: 10022891 - Investigations
MedDRA version: 21.0 Level: PT Classification code 10030155 Term: Oesophageal carcinoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 20.1 Level: LLT Classification code 10017770 Term: Gastric carcinoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 20.0 Level: PT Classification code 10042863 Term: Synovial sarcoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 20.0 Level: LLT Classification code 10064467 Term: Urothelial carcinoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 21.1 Level: LLT Classification code 10033131 Term: Ovarian carcinoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 21.1 Level: PT Classification code 10061873 Term: Non-small cell lung cancer
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2018-003120-36-ES

Lead Sponsor: Immunocore Limited

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: Not specified

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. In the opinion of the Investigator, all other relevant medical conditions must be stable and well-managed for at least 28 days prior to first drug administration
6. HLA-A*02:01 positive (testing by central laboratory)
7. MAGE-A4-positive tumor (testing by central laboratory)
8. Patients enrolling in biomarker backfill cohorts must have disease that is amenable to biopsy and consent to undergo biopsies during Screening and on treatment
9. Patients 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
10. Patients with metastatic/unresectable NSCLC, esophageal, gastric, urothelial, HNSCC, ovarian, or synovial sarcoma are eligible. Patients must meet the indication-specific histology and biomarker testing requirements specified in the protocol
11. 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.
12. Male and female patients who are sexually active with a non-sterilized 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 = 4 weeks after intervention (surgery and/or radiation)
• Patients must be neurologically stable off systemic corticosteroids for receiving systemic corticosteroids or have received systemic corticosteroids within 3 weeks prior to enrollment
2. 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).
3. 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 immunotherapy
• imAE requiring immunosuppressive treatments other than corticosteroids
• imAE that recurred upon rechallenge
• Any neurological or ocular imAE
4. 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 Section 5.3.
• Immunotherapies (eg, atezolizumab, pembrolizumab, ipilimumab): 28 days
• HER2-targeted antibodies (eg, trastuzumab): 28 days
• All other systemic therapies: 14 days
• Radiotherapy: 14 days (excepting palliative radiotherapy to a limited field, which is permitted at any time)
5. Patient with an out-of-range Screening laboratory values defined as shown below
• Creatinine clearance (calculated using Cockcroft-Gault formula, or measured) < 50 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
6. History of interstitial lung disease or severe chronic obstructive pulmonary disease (forced expiratory volume in less than 1 second = 50% of predicted)
7. Clinically significant cardiac disease or impaired cardiac function, including any of the following:
• Uncontrolled hypertension (systolic blood pressure [BP] > 160 mmHg or diastolic BP > 110 mmHg despite treatment with appropriate anti-hypertensive treatment)
•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 congenital prolonged QT syndrome
• Cardiac troponin T > ULN at Screening
• Acute myocardial infarction or unstable angina pectoris = 6 months p

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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