A Modular, Multi-part, Multi-arm, Open-label, Phase I/II Study to Evaluate the Safety and Tolerability of GRWD5769 Alone and in Combination with Anticancer Treatments in Patients with Solid Malignancies

Phase 1

Recruiting

• Conditions: Solid malignancies; MedDRA version: 21.1Level: LLTClassification code: 10065147Term: Malignant solid tumor Class: 10029104; MedDRA version: 21.1Level: LLTClassification code: 10065143Term: Malignant solid tumour Class: 10029104; Therapeutic area: Diseases [C] - Neoplasms [C04]

• Registration Number: CTIS2023-504845-30-00
• Lead Sponsor: Grey Wolf Therapeutics Limited

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2023-06-02
• Last Update Posted: 22 July 2024

Recruitment & Eligibility

• Status: Recruiting
• Sex: All
• Target Recruitment: 288

Inclusion Criteria

All Modules: Must have given written informed consent before any study-related activities are carried out and must be able to understand the full nature and purpose of the trial, including possible risks and adverse effects., All Modules: Willing to permit access to stored historical tumour tissue and prior tumour radiological assessments and tumour biomarker data (if available)., All Modules: Able to take oral medications and be willing to record daily adherence to the study drug., All Modules: Female participants must be of non-childbearing potential i.e., surgically sterilised (hysterectomy, bilateral salpingectomy, bilateral oophorectomy at least 6 weeks before the screening visit) or post-menopausal (where post-menopausal is defined as no menses for 12 months without an alternative medical cause and a folliclestimulating hormone (FSH) level consistent with post-menopausal status, per local laboratory guidelines), or, if of childbearing potential: a. Must have a negative serum pregnancy test at the screening visit and a negative urine pregnancy test within 24 hours prior to the start of study drug b. Must agree not to attempt to become pregnant c. Must not donate ova from signing consent until at least: i. 33 days (30 days + minimum of 5 × half-lives of GRWD5769) after the last dose of study drug (Module 1) ii. 6 months after the last dose of cemiplimab (Module 2 or Module 1 Part A crossover) d. If not exclusively in a same sex relationship, must agree to use adequate contraception (which is defined as use of a condom by the male partner combined with use of a highly effective method of contraception [Section 23.1]) from signing the consent form until at least: i. 33 days after the last dose of study drug (Module 1) ii. 6 months after the last dose of cemiplimab (Module 2 or Module 1 Part A crossover), All Modules: Male participants must: a. Agree not to donate sperm from the time of signing consent until at least 93 days (90 days + minimum of 5 x half-lives of GRWD5769) after the last dose of study drug; b. If engaging in sexual intercourse with a female partner who could become pregnant, must agree to use a condom plus a highly effective method of contraception (Section 23.1) from the time of signing consent until at least 93 days after the last dose of study drug; c. If engaging in sexual intercourse with a female partner who is not of childbearing potential or a same-sex partner, must agree to use a condom from the time of signing consent until at least 93 days after the last dose of study drug., All Modules: Estimated life expectancy of at least 3 months, in the opinion of the PI., All Modules: Willing and able to comply with all scheduled visits, treatment plans, laboratory tests, and other study procedures., Module 2 (Part C) Cohort 2: Participants with histologically confirmed hepatocellular carcinoma who are not amenable to curative therapy and ineligible for loco-regional therapy., Module 2 (Part C) Cohort 2: Participants should have received at least 3 months first line anti-PD(L)-1 containing therapy and a scan done 6 weeks or more after starting therapy that did not demonstrate progression (per physician assessment) but have now progressed on anti- PD(L)-1 therapy., Module 2 (Part C) Cohort 2: Participants may enrol in the study immediately following progression on the first line CPI or may have received 1 further line of systemic cancer therapy after progression on CPI., Module 2 (Part C) Cohort 2: Participant has Chi

Exclusion Criteria

All Modules: Prior therapy with an ERAP1 inhibitor, within any timeframe prior to the first dose of IMP., All Modules: Liver function deteriorating in a manner that would likely make the participant meet the AST, ALT, or bilirubin levels specified above prior to the day of the first dose of IMP., All Modules: Other evidence of impaired hepatic synthesis function, All Modules: Any other malignancy not meeting inclusion criterion #10 (Module 1 Parts A, B, and C and Module 2 Part A and B), or inclusion criteria #13, 16 or 20 (Module 2 Part C) which has been active or treated within the past 3 years, with the exception of cervical intraepithelial neoplasia and non-melanoma skin cancer., All Modules: Inadequate bone marrow reserve or organ function as demonstrated by any of the following laboratory values: a. Absolute neutrophil count (ANC) < 1.5 × 109/L. b. Platelet count < 100 × 109/L. c. Haemoglobin < 90 g/L., All Modules: Any prior history of persistent (> 4 weeks) severe pancytopenia due to previous therapy rather than to disease (ANC < 0.5 × 109/L or platelets < 50 × 109/L)., All Modules: Cardiac dysfunction (defined as myocardial infarction within the last 6 months, New York Heart Association Class II/III/IV heart failure, unstable angina, unstable cardiac arrhythmias, or known left ventricular ejection fraction < 55%) or other clinically significant cardiac pathology likely to impair the participants ability to participate in the study. Participants with low normal LVEF (50-55%) are eligible if there is no evidence of significant cardiomyopathy or valvular disease on echo (or other imaging) and no significant clinical symptoms of heart failure., All Modules: Mean QTcF > 450 ms for males or > 470 ms for females at both screening and prior to the first dose of IMP (on the day of first dose administration) (the mean of triplicate measurements [within 10 minutes with each reading separated by 1-5 minutes] will be used to determine eligibility)., All Modules: Any clinically important abnormalities in rhythm, conduction, or morphology on resting ECG (e.g., complete left bundle branch block, third degree heart block). Controlled atrial fibrillation is permitted., All Modules: Any factor that in the Investigator’s opinion increases the risk of QTc prolongation or arrythmic events., All Modules: In the opinion of the Investigator, unlikely to comply with study procedures, restrictions, or requirements., All Modules: Participant has received an organ transplant., All Modules: A history of haemolytic anaemia or marrow aplasia, All Modules: Has received a live virus vaccination within 28 days or less of planned treatment start. Note: seasonal flu or COVID vaccines that do not contain live virus are permitted, All Modules: History of Grade 3 or 4 pneumonitis or interstitial lung disease within the last 5 years, or other clinically significant pulmonary pathology likely to impair ability to participate in the study., All Modules: Any unresolved toxicity (except alopecia) from prior therapy of = CTCAE Grade 1, prior to the day of the first dose of IMP. Participants with Grade 2 toxicity that is not clinically significant (e.g., alopecia, vitiligo), or that is deemed stable or irreversible (e.g., peripheral neuropathy) can be enrolled., Module 2 all Parts and Module 1A Crossover Participants Only: Has discontinued a prior checkpoint inhibitor due to toxicity., Module 2 all Parts and Module 1A Crossover Participants Only: Hypersensitivity to cemiplim

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified