2024-514826-22-00招募中2 期
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
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 70
- 试验地点
- 10
- 主要终点
- Part A: Occurrence of dose limiting toxicity (DLT) for MTD determination and/or RP2D.
研究概览
简要总结
Part A: To determine the Maximum Tolerated Dose (MTD) and/or the Recommended Phase 2 Doses (RP2D) when administered as single IV infusion on every 3 or 6 weeks. 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.
研究设计
- 研究类型
- Interventional
入排标准
- 年龄范围
- 18 years 至 65+ years（65+ Years, 18-64 Years）
- 接受健康志愿者
- 否
入选标准
- •Male or female adult patients (≥ 18 years).
- •Part B and C: Tumor type: a.Histologically or cytologically documented Stage IV squamous or non-squamous 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.
- •Part B and C: 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.
- •Part B and C: Patients with at least one measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.
- •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.
- •ECOG performance status 0-
- •Part A: Tumor type: a. 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; b. 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; c.PD-L1 positive tumors.
- •Part A: Prior treatment with at least one line of systemic therapy and no standard of care available.
- •Part A: Evaluable or measurable disease according to RECIST 1.1/RECIL.
- •Adequate organ function: a. Bone marrow: neutrophils ≥ 1.5 x 10^9/L, hemoglobin ≥ 90 g/L, platelets ≥ 100 x 10^9/L; 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.
- •Patients must be affiliated to a social security system or an equivalent system, if applicable as per local regulations.
- •Part B and C: 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.
排除标准
- •Patient eligible to surgical resection or another approved therapeutic regimen known to provide clinical benefit.
- •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.
- •Patient with organ(s) transplant including hematopoietic stem cell allograft.
- •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, mAb: 4 week; b. 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; c. 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; d. Recent major surgery within the previous 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 (except low-dose up to a total dose equivalent to prednisolone 10 mg/day).
- •Patients with hypersensitivity to OSE-279/OSE2101 or any of its excipients.
- •Patients with active tuberculosis (Mycobacterium tuberculosis).
- •Patients with: a. Active hepatitis B (defined as Hbs Ag+ and/or anti-HBc+ and HBV DNA+); b. Active hepatitis C (anti-HCV+ and HCV RNA+); c. Active HIV infection: HIV+ patients on highly active antiretroviral therapy (HAART) are eligible if PCR for HIV is negative at screening; d. Presence of signs/symptoms suggestive of active infection (including COVID-19 infection).
- •Patients with known psychiatric or substance abuse disorders that would interfere their ability to comply with protocol requirements.
- •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 8 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.
- •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 8 months after the last dose of trial treatment.
- •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.
- •Patient previously treated with an approved or investigational anti-PD-1/PD-L
- •Part B and C: Small-cell lung cancer/mixed NSCLC with small cell component or other neuroendocrine lung cancers (typical and atypical carcinoids, large-cell neuroendocrine carcinomas).
- •Part B and C: Patients with hypersensitivity to OSE-279 or OSE-2101 or any of one of their excipients.
- •Part B and C: Patients previously treated with anti-PD-L2, anti-CD137, or anti-Cytotoxic T-Lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways).
- •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.
- •Patient participating in another clinical trial with a medicinal product.
- •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-
- •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 non-inclusion criteria.
- •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 C1D
- •Patients with active or history of non-infectious pneumonitis requiring steroids, or interstitial lung disease.
- •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.
结局指标
主要结局
Part A: Occurrence of dose limiting toxicity (DLT) for MTD determination and/or RP2D.
Part A: Occurrence of dose limiting toxicity (DLT) for MTD determination and/or RP2D.
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 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.
Part C: ORR: Complete Response (CR) and Partial Response (PR) rate.
次要结局
- Part A: Efficacy (Objective Response Rate (ORR): Complete Response (CR) and Partial Response (PR) rate ; Disease Control 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; Overall Survival (OS)).
- Part A: Pharmacokinetics and Pharmacodynamics (OSE-279 Pharmacokinetic parameters; Detection of anti-OSE-279 antibodies).
- 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).
- Part B: 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).
- Part C: Safety (Nature, incidence and severity of TEAE (including DLT like events and AESI), of SAE, SUSARs graded according to CTCAE grading version 5.0).
研究者
Lucie BEGERT
Scientific
OSE Immunotherapeutics
研究点 (10)
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