A Multicenter, Open-Label, Phase I/II Study of EOS884448 in combination with standard of care and/or investigational therapies in participants with advanced solid tumors
- Conditions
- Therapeutic area: Diseases [C] - Cancer [C04]Advanced solid tumors
- Registration Number
- EUCTR2021-001329-29-BE
- Lead Sponsor
- iTeos Belgium SA
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 276
1. Provide a signed written informed consent for the trial and consent for biopsies before and during administration of study treatment at Cycle 2 with an optional consent for biopsy at Cycle 5 and at disease progression, if applicable.
Note: For Part 1G, Part 2C & 2D only: biopsies are optional, therefore consent for biopsies is optional
2. Be =18 years of age on day of signing informed consent.
3. Have measurable disease, per RECIST v1.1 for solid tumor (Appendix 8.1) based on local assessment.
4. Have a predicted life expectancy of = 16 weeks.
5. Have an Eastern Cooperative Oncology Group (ECOG) performance status of Grade 0 or 1 (Appendix 8.2).
6. Have adequate organ function as defined by the following criteria collected within 10 days prior to start of study treatment. A participant not qualifying for any of these parameters on the initial screening assessment can be considered eligible providing that recovery is expected during the screening period and the criteria above are met prior to the start of therapy (Note: please refer to inclusion criterion #13 specific to Part 1G):
a. Serum albumin = 30 g/L (3.0 g/dL)
b. Hemoglobin = 9.0 g/dL or = 5.6 mmol/L
c. Platelet count = 100 × 109/L
d. Absolute neutrophil count = 1.2 × 109/L
e. Measured or calculated creatinine clearance = 30 mL/min for Parts 1A, 1D, 2A, 2B, 2C, 2D and = 60 mL/min for Part 1B, 1C, 1E, 1F and 2E, using the formula of Cockroft and Gault (1976).
f. Adequate hepatic function within 28 days prior to C1D1: Total bilirubin < 1.5 X ULN (except participants with Gilbert's syndrome [hereditary indirect hyperbilirubinemia] who must have a total bilirubin of = 2.5 X ULN (upper limit of normal)) and both AST (aspartate transaminase) and ALT (alanine transaminase) < 3.0 X ULN.
g. International normalized ratio (INR) = 1.5 × ULN unless participant is receiving anticoagulant therapy provided that prothrombin time (PT) or activated partial thromboplastin time (aPTT) is within therapeutic range of intended use of anticoagulants.
7. Female participants of childbearing potential (defined as women with < 12 continuous months of amenorrhea with no identified cause other than menopause, or not surgically sterile), must have a negative pregnancy test within 7 days before the first administration of study treatment and agree to use highly efficient contraception, as defined in Appendix 8.5, during the treatment and until 60 days after the last administration of EOS-448 or inupadenant, 120 days after the last administration of pembrolizumab or dostarlimab whichever applicable date is the latest. Prolonged period may be required in case of chemotherapy according to summary of product characteristics (SmPC), package insert or equivalent document for the specific country/region and should follow local standard of care (SOC) beyond 120 days.
8. Male participants with female partner(s) of childbearing potential must agree to remain sexually abstinent or use condoms during the treatment and 120 days after the last dose of the study medication whichever applicable date is the latest. Prolonged period may be required in case of chemotherapy according to SmPC and should follow local SOC beyond 120 days. In addition, male participants must forego sperm donation during this time.
Additional inclusion criteria for Parts 1A, 1B, 1C, 1D, 1E and 1F (advanced solid tumors):
9. Have histologically or cytologically confirmed advanced or metastatic solid tumor for whom no standard treatment with survival
2. Have received a live vaccine within 30 days prior to the first dose of study treatment. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette–Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., FluMist®) are live attenuated vaccines and are not allowed. All approved COVID-19 vaccines are authorized unless otherwise indicated by the sponsor.
3. Have known primary Central Nervous System (CNS) cancer.
4. Have known CNS metastases (including leptomeningeal disease) except for the following:
a. Participants with previously treated CNS metastases that are well controlled for at least one month (defined as clinically stable, no edema, no steroid dose increases for 4 weeks and stable on 2 scans at least 4 weeks apart), are allowed.
b. Participants with known CNS metastases for whom the treating physician determines that immediate CNS specific treatment is not required and is unlikely to be required during the first cycle of therapy are allowed.
c. In case of known CNS metastases, baseline CNS imaging must be obtained up to 4 weeks before the start of the study treatment to document CNS metastases measurements.
6. Have received lung radiation therapy of >30 Gy within 6 months of the first dose of study treatment.
7. Have a history of Grade = 2 pneumonitis, active autoimmune disease, or persistent immune-mediated toxicity caused by immune checkpoint inhibitor therapy of Grade = 2 with the exception of residual endocrinopathy adequately substituted, vitiligo, Type 1 diabetes mellitus, or psoriasis not requiring systemic therapy.
8. Have toxicity (except for alopecia) related to prior anti-cancer therapy and/or surgery, unless the toxicity is either resolved, returned to baseline or Grade 1, or deemed irreversible.
9. Have any active neuropathy > Grade 2 (CTCAE v5.0).
10. Have history of grade 3 or higher liver toxicity or life-threatening toxicity related to prior immune therapy or any toxicity that resulted in permanent discontinuation of prior immune therapy.
11. Have any condition requiring concurrent use of systemic immunosuppressants or corticosteroids > 10 mg daily prednisone equivalents or other immunosuppressive medications within 14 days of study treatment administration (permitted: premedication/prophylaxis if indicated, e.g. for IV contrast, treatment with a short course of steroids [< 5 days] up to 7 days before initiating study treatment, topical glucocorticoids, or steroid replacement doses for adrenal insufficiency).
12. Have evidence of active infection that requires systemic antibacterial, antiviral, or antifungal therapy = 7 days before the first dose of study treatment (except for viral infections that are presumed to be associated with the underlying tumor type required for study entry).
13. Have uncontrolled or significant cardiovascular disease including, but not limited to, any of the following:
a. Left ventricular ejection fraction = 50% determined by echocardiogram or other approved method of evaluation
b. Myocardial infarction within the past 2 years
c. Uncontrolled angina within the past 6 months
d History of clinically significant arrhythmias (such as atrial fibrillation and conduction disorders, ventricular tachycardia, ventricular fibrillation). For part 1G and 2C/2D, participa
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