Dose-finding and Dose Expansion Study of OSE-279 in Subjects With Advanced Solid Tumors or Lymphomas

Study Overview
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Brief Summary
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This is a phase 1/2, multicenter, dose-finding and dose expansion study of OSE-279, a PD-1 blocking monoclonal antibody, in subjects with advanced solid tumors or lymphomas.

Official Title
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A Multicenter, Phase 1/2, Dose-finding and Dose Expansion Study of OSE-279, a PD-1 Blocking Monoclonal Antibody, in Subjects With Advanced Solid Tumors or Lymphomas

Conditions
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Solid Advanced Tumor, Lymphoma

Intervention / Treatment
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* Drug: OSE-279 100mg
* Drug: OSE-279 300mg
* Drug: OSE-279 500mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria (I): I-1. Male or female adult patients. I-2. Signed and dated informed consent form (ICF) prior to any trial-specific procedures. Patients should be able and willing to comply with study visits and procedures as per protocol. I-3. ECOG performance status 0-1. I-4. Tumor type: advanced solid tumors or lymphomas for which an anti PD-1/PD-L1 has shown efficacy (e.g., with high microsatellite instability or MSI-H) but is not available in the center/country (no marketing authorization, no reimbursement, no early access program, etc.) or; rare tumors with reported significant activity of anti-PD-1 (e.g., Tertiary Lymphoid Structures positive or TLS+ sarcomas, alveolar soft part sarcomas, etc.), or; PD-L1 positive tumors. I-5. Prior treatment with at least one line of systemic therapy and no standard of care available. I-6. Evaluable or measurable disease according to RECIST 1.1/RECIL. I-7. Adequate organ function: Bone marrow: neutrophils ≥ 1.5 x 109/L, hemoglobin ≥ 90 g/L, platelets ≥ 100 x 109/L. Renal function: serum creatinine ≤ 1.5 ULN or CKD-EPI creatinine clearance ≥ 30 mL/min. Liver function: AST and ALT ≤ 3 ULN, bilirubin ≤ 1.5 ULN. In case of liver metastasis: AST and ALT ≤ 5 ULN. For patients with Gilbert's syndrome total bilirubin ≤ 3 ULN or direct bilirubin ≤ 1.5 ULN. I-8. Patients must be affiliated to a social security system or an equivalent system, if applicable as per local regulations. Non-Inclusion Criteria (NI): NI-1. Patient eligible to surgical resection or another approved therapeutic regimen known to provide clinical benefit. NI-2. Patient previously treated with an approved or investigational anti-PD-1/PD-L1. NI-3. Patient with active autoimmune disease or a documented history of autoimmune disease requiring systemic treatment (i.e., corticosteroids or immunosuppressive drugs); except autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone, controlled hypophysitis, controlled Type 1 diabetes mellitus on a stable insulin regimen, vitiligo, resolved childhood asthma/atopy, alopecia, or any chronic skin condition not requiring systemic therapy. NI-4. Patient participating in another clinical trial with a medicinal product. NI-5. Patients who have not recovered from adverse events (i.e., > Grade 1 according to CTCAE v5.0) due to prior treatment with anti-cancer agents with exception of Grade 2 neuropathy or any Grade alopecia. Lab values must be within the limits presented in criterion I-7. NI-6. Patients with known additional malignancy progressing or requiring active treatment. Basal cell carcinoma, squamous cell carcinoma of the skin, or in situ cervical cancer are not a non-inclusion criteria. NI-7. Patients with known active central nervous system metastases and/or carcinomatous meningitis. Patients with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least 4 weeks prior to C1D1 and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids (at doses higher than 10 mg/day of methylprednisolone or equivalent) for at least 4 weeks prior C1D1. NI-8. Patients with active or history of non-infectious pneumonitis requiring steroids, or interstitial lung disease. NI-9. Patients with a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the patient's participation for the full duration of the study. NI-10. Patients with a history of uncontrolled or symptomatic, clinically significant cardiovascular disease: stroke, myocardial infarction, angina pectoris, arrhythmias, congestive heart failure (NYHA Class >2), or myocarditis within 6 months prior to first study drug administration. NI-11. Patient with organ(s) transplanted including hematopoietic stem cell allograft. NI-12. Patients receiving or to be treated during the treatment period with one of the following forbidden treatments: Any anti-cancer systemic chemotherapy, targeted therapy or biological therapy including any immunotherapy not mentioned in this protocol. Washout prior to screening: chemotherapy: 3 weeks (6 weeks for nitrosourea), TKi or other small molecules: 2 weeks or 5 half-lives whichever is shortest, mAb: 4 weeks. Radiation therapy (washout prior to screening: 7 days prior to Cycle 1). Note: Radiation therapy to a symptomatic solitary non target lesion or to the brain may be allowed after consultation with Sponsor. Live vaccines. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, chicken pox, yellow fever, rabies, tuberculosis (BCG), and typhoid (oral) vaccines. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are not allowed. Recent major surgery within the previous 3 months. Systemic corticosteroids for any purpose other than to modulate symptoms from an event of clinical interest of suspected immunologic etiology. The use of physiologic doses of corticosteroids may be approved after consultation with the Sponsor. Immunosuppressive agents such as steroids should be tapered off before initiation of study treatment (except low-dose up to a total dose equivalent to prednisolone 10 mg/day). NI-13. Patients with hypersensitivity to OSE-279 or any of its excipients. NI-14. Patients with active tuberculosis (Mycobacterium tuberculosis). NI-15. Patients with: Active hepatitis B (defined as HBsAg+ and/or HBVc+ and HBV DNA+). Active hepatitis C (anti-HCV+ and HCV RNA+). Active HIV infection: HIV+ patients on highly active antiretroviral therapy (HAART) are eligible if PCR for HIV is negative at screening. Presence of signs/symptoms suggestive of active infection (including COVID-19 infection). NI-16. Patients with known psychiatric or substance abuse disorders that would interfere their ability to comply with protocol requirements. NI-17. WOCBP and men participating in the study (and their partners) must agree to follow the precautions to avoid gestational problems, by using highly efficient contraception throughout the study and until 4 months after the last administration of investigational treatment based on CTFG guidance. In addition, during this study period men should use condoms and avoid semen donation. NI-18. Women who are pregnant or breast-feeding or women/men expecting to conceive children within the projected duration of the trial, starting with the screening visit through 4 months after the last dose of trial treatment. NI-19. Vulnerable persons, if applicable as per local regulations, such as individuals under the protection of a legal guardian, pregnant or breastfeeding women, persons in custody by judicial or administrative decision, persons under psychiatric care without consent, persons admitted in a healthcare facility or social institution not for research purposes, minors, individuals unable to state their consent.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: OSE-279 100 mg<br>Dose Level 1: OSE-279 100 mg | Drug: OSE-279 100mg<br>* Human IgG4 mAb against PD-1<br>|
| Experimental: OSE-279 300 mg<br>Dose Level 2: OSE-279 300 mg | Drug: OSE-279 300mg<br>* Human IgG4 mAb against PD-1<br>|
| Experimental: OSE-279 500 mg<br>Dose Level 3: OSE-279 500 mg | Drug: OSE-279 500mg<br>* Human IgG4 mAb against PD-1<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Occurrence of dose limiting toxicity (DLT) | Occurrence of dose limiting toxicity (DLT) | DLT observation period is defined as the first 21 days after receiving the 1st injection of OSE-279 (Cycle 1) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) | Objective Response Rate (ORR): complete response (CR) and partial response (PR), based on RECIST 1.1/RECIL and iRECIST | Through study completion, an average of 1 year | 
| Disease Control Rate (DCR: CR, PR and SD) | Disease Control Rate (DCR): complete response (CR), partial response (PR) and stable disease (SD) based on RECIST 1.1/RECIL and iRECIST | Through study completion, an average of 1 year | 
| Time to response | Time to response | From start of treatment until date of first occurence of response (CR or PR based on RECIST 1.1/RECIL and iRECIST), an average of 1 year | 
| Duration of response (DR) | Duration of response (DR) | From the first assessment of CR or PR until the date of the first occurrence of PD, or until the date of death (up to 1 year) | 
| Progression Free Survival (PFS) | Progression Free Survival (PFS) | From start of treatment until date of progression based on RECIST 1.1/RECIL and iRECIST or date of death (up to 1 year) | 
| DCR at 12 weeks (CR+PR+SD) | DCR at 12 weeks (CR+PR+SD) | Up to 12 weeks | 
| Overall Survival (OS) | Overall Survival (OS) | From start of treatment to Death (up to 2 years) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Solid advanced tumor, Lymphoma, Rare tumor, PD-L1 positive tumor, PD-1 blocking monoclonal antibody