Advanced solid tumors and lymphomas MedDRA version: 21.1 Level: LLT Classification code 10065143 Term: Malignant solid tumour System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 20.0 Level: LLT Classification code 10025055 Term: Lung cancer non-small cell stage IV System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 20.0 Level: LLT Classification code 10079440 Term: Non
Conditions
Interventions
Product Name: OSE-279
Product Code: OSE-279
Pharmaceutical Form: Concentrate for solution for infusion
Product Name: OSE2101
Product Code: OSE2101
Pharmaceutical Form: Emulsion for injection
Sponsors
OSE Immunotherapeutics
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Part A, B and C: 1. Male or female adult patients (= 18 years at the time of ICF signature). 2. Signed and dated informed consent (ICF) prior to any trial-specific procedures. Patients should be able and willing to comply with study visits and procedures as per protocol. 3. Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1. 4. Tumor type: a. advanced solid tumors or lymphomas for which 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; b. rare tumors with reported significant activity of anti-PD1 (e.g., TLS+ sarcomas, alveolar soft part sarcomas, etc.), or; c. PD-L1 positive tumors. 5. Prior treatment with at least one line of systemic therapy and no standard of care available. 6. Evaluable or measurable disease according to RECIST 1.1/RECIL (Ribrag 2017). 7. Patient with adequate organ function: a. Bone marrow: neutrophils = 1.5 x 10^9/L, hemoglobin = 90 g/L, platelets = 100 x 10^9L. b. Renal function: serum creatinine = 1.5 ULN or CKD-EPI creatinine clearance = 30 mL/min. c. 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. 8. Patients must be affiliated to a social security system or an equivalent system, if applicable as per local regulations. Part B and C: In addition to the inclusion criteria of PART A: 9. Patients expressing HLA-A2 phenotype on blood sample performed by an experienced laboratory using a validated test.(PCR or NGS); Additional patients HLA-A2 negative will be included in Part C. 10. Tumor type: a. Histologically or cytologically documented Stage IV squamous or nonsquamous NSCLC not eligible for definite surgery or radiation, which does not have EGFR sensitizing (activating) mutation or ALK and ROS1 gene alterations eligible for targeted therapy or other mutations for which an approved therapy exists in 1st line metastatic setting (i.e.; KRAS G12C, RET, MET SKIP14, BRAFV600E mutations). b. Documented PD-L1 expression by TPS = 50% by local testing. 11. Patients must not have received prior systemic therapy including immunotherapy in the first-line metastatic setting; Completion of treatment with chemotherapy and/or radiation as part of neoadjuvant/adjuvant therapy is allowed as long as therapy was completed at least 6 months prior to the diagnosis of metastatic disease. 12. Patients with at least one measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. 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 47 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 8
Exclusion criteria
Exclusion criteria: Part A, B and C: 1.Patient eligible to surgical resection or another approved therapeutic regimen known to provide clinical benefit 2. Patient previously treated with an approved or investigational anti-PD-1/PD-L1. 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. 4. Patient participating in another clinical trial with a medicinal product. 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 7. 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 exclusion criteria. 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, have no evidence of new or enlarging brain metastases, and are not using steroids for at least 4 weeks prior C1D1. 8. Patients with active or history of non-infectious pneumonitis requiring steroids, or interstitial lung disease. 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. 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. 11. Patient with organ(s) transplanted including stem cell allograft. 12. Patients receiving or to be treated during the treatment period with one of the following forbidden treatments. a. 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, mAbs: 4 weeks. b. Radiation therapy (washout prior to screening: 7 days prior to Cycle 1). c. Live vaccines. d. Recent major surgery (<3 months). e. 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. 13. Patients with hypersensitivity to OSE-279 or any of its excipients. 14. Patients with active tuberculosis. 15. Patients with: Active hepatitis B, Active hepatitis C, Active HIV infection: HIV+ patients on highly active antiretroviral therapy are eligible if PCR for HIV is negative at screening, Presence of signs/symptoms suggestive of active infection (including COV
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Part A: To determine the Maximum Tolerated Dose (MTD) and/or the Recommended Phase 2 Doses (RP2D). Part B: To evaluate the safety and tolerability of the combination OSE-279/OSE2101. Part C: To assess the antitumor activity of OSE-279 in combination with OSE2101 versus 0SE-279 in terms of overall response rate (ORR) as assessed locally, in patients with 1st line metastatic (stage IV) NSCLC.;Secondary Objective: Part A: To assess the antitumor activity; To evaluate the safety profile; To evaluate the pharmacokinetic (PK) profile; To evaluate immunogenicity (ADA). Part B: To preliminary determine the antitumor activity of the combination (ORR, DCR, DOR, TTR, DCR at 12 weeks and 24 weeks, PFS, OS and OS at 12 months). Part C: To further assess the efficacy of the combination of OSE-279/OSE2101 versus OSE-279 with respect to DCR,TTR, DOR, PFS, DCR at 12 weeks and 24 weeks, OS and OS rate at 12 months; To further evaluate the safety profile of both treatment groups.;Primary end point(s): Part A: Occurrence of dose limiting toxicity (DLT). Part B: Occurrence of dose limiting toxicity (DLT) where DLT observation period is defined as the first 6 weeks after receiving the first injections of OSE-279 and of OSE2101. Part C: ORR: Complete Response (CR) and Partial Response (PR) rate.;Timepoint(s) of evaluation of this end point: Part A: DLT observation period is defined as the first 21 days after receiving the 1st injection of OSE-279. Part B: DLT observation period is defined as the first 6 weeks after receiving the first injections of OSE-279 and of OSE2101. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Part A: • Efficacy: Objective Response Rate (ORR: CR and PR); Disease Control Rate (DCR: CR, PR and SD); Time to response; Duration of response (DR); Progression Free Survival (PFS); DCR at 12 weeks (CR+PR+SD); Overall Survival (OS). • Pharmacokinetics and Pharmacodynamics: Pharmacokinetic parameters; Detection of anti-OSE-279 antibodies. • Safety: Nature, incidence and severity of TEAE (including DLT and AE of special Interest (AESI)), of SAE, SUSARs graded according to CTC-AE grading. Part B: • Efficacy: ORR: Complete Response (CR) and Partial Response (PR) rate; DCR: CR, PR and Stable Disease (SD) rate; Time to response (TTR); Duration of Objective Response (DOR); Progression Free Survival (PFS); DCR (CR+PR+SD) at 12 weeks and 24 weeks; Overall Survival (OS); OS rate at 12 months. • Safety: Nature, incidence and severity of TEAE (including DLT and AE of special Interest (AESI)), of SAE, SUSARs graded according to CTCAE grading v5.0. Part C: • Efficacy: DCR: CR, PR and Stable Disease (SD) rate; Time to response (TTR); Duration of Objective Response (DOR); Progression Free Survival (PFS); DCR (CR+PR+SD) at 12 weeks and 24 weeks; Overall Survival (OS); OS rate at 12 months. • Safety: Nature, incidence and severity of TEAE (including DLT like events and AESI), of SAE, SUSARs graded according to CTCAE grading version 5.0.;Timepoint(s) of evaluation of this end point: Part A: Assessments throughout the entire Part A duration. Part B: Assessments throughout the entire Part B duration. Part C: Assessments throughout the entire Part C duration. | — |
Countries
Belgium
Contacts
Public ContactOSE Contact
OSE Immunotherapeutics
Outcome results
None listed