A Multicenter, Open-label, Proof of Concept Phase II Aiming to Assess the Clinical and Biological Activity of Anti-netrin-1 (NP137) as Add on Therapy in Patients With Advanced/Metastatic Solid Tumors Treated by Standard Immunotherapies
概览
- 阶段
- 2 期
- 干预措施
- NP137
- 疾病 / 适应症
- Advanced Solid Tumors
- 发起方
- Centre Leon Berard
- 入组人数
- 57
- 试验地点
- 5
- 主要终点
- Objective Response Rate (ORR-12W)
- 状态
- 进行中（未招募）
- 最后更新
- 8天前
概览
简要总结
This study is a multicenter, open-label, proof-of-concept study aiming to assess the clinical and biological impact of NP137 when added to standard PD-1/PD-L1 blockade therapy in 3 independent cohorts of advanced or metastatic solid tumors with various sensitivity to anti-PD-1/PD-L1:
- Cohort 1 [Stable Disease]: Patients with a radiological documentation of SD according to RECIST V1.1 criteria following at least 12 weeks under standard anti PD-1/PD-L1 therapy. Note: This treatment arm closed on 27/09/2024 due to non-feasibility.
- Cohort 2 [primary refractory]: Patients with documented radiological PD or short-term SD (< 6months) according to RECIST V1.1 but with clinical benefit under PD-1/PD-L1 standard therapy.
- Cohort 3 [secondary refractory]: Patients with documented radiological PD following an initial Objective Response or long-term SD (i.e. ≥6 months) according to RECIST V1.1, with clinical benefit under standard PD-1/PD-L1.
详细描述
To be eligible to cohort 1 \[stable disease\], the initial evidence of SD is to be confirmed by a second assessment, no less than 4 weeks from the date of the first documented SD. To be eligible to cohorts 2 and 3 \[primary and secondary refractory patients\], patients must meet all the following criteria: * Evidence of clinical benefit according to investigator assessment. The assessment of clinical benefit should be balanced by clinical judgment as to whether the patient is clinically deteriorating and unlikely to receive any benefit from continued anti-PD-1/PD-L1 treatment. * Absence of symptoms and signs (including laboratory values, such as new or worsening hypercalcemia) indicating unequivocal progression of disease, * Absence of decline in ECOG PS that can be attributed to disease progression, * Absence of tumor progression at critical anatomical sites (e.g., leptomeningeal disease) that cannot be managed by protocol-allowed medical interventions. * No ongoing clinically significant AE related to anti-PD-1/PD-L1. During this study: * All patients will receive NP137 (14 mg/kg, IV, Q3W) as add-on treatment to their standard anti-PD1 or anti-PDL1 treatment administered. * To facilitate the study treatments administration and to not over burden patients, the study drug NP137 which is administered every 3 weeks (Q3W) will be associated to standard PD-1/PD-L1 therapies for which dosing are administered every 3 weeks or every 6 weeks (Q3W or Q6W). A treatment delay of up to 3 days is allowed before the start of a new cycle.
研究者
入排标准
入选标准
- •Male or female patients aged ≥ 18 years at time of inform consent signature.
- •Patient with histologically confirmed locally advanced / metastatic solid tumors of any histological types
- •Patients treated with standard anti-PD-1/PD-L1 (e.g. pembrolizumab, atezolizumab, or any other ICI to be approved and reimbursed in France during the course of this trial, with a Q3W or Q6W schedule, either as monotherapy or in combination with chemotherapies according to their approved label). A positive list of eligible solid tumour types together with the associated anti-PD-1/PD-L1 standard therapy approved for each indication is provided in appendix
- •For any pathology not listed in this appendix but for which an anti-PD-1/PD-L1 has newly obtained a MA and is now reiumbursed in France, please refer to the section 0 of this protocol) and meet the following criteria :
- •I3a. Cohort 1: Patient with RECIST 1.1.-defined SD under at least 12 weeks anti-PD-1/PD-L
- •The initial evidence of SD is to be confirmed by a second assessment, no less than 4 weeks from the date of the first documented SD. Stable disease must be the best response observed since initiation of anti-PD-1/PD-L1 standard therapy or induction phase.
- •I3b. Cohort 2: Patient with RECIST 1.1-defined PD under anti-PD-1/PD-L1 or short-term SD i.e. \< 6 months as best response under anti-PD-1/PD-L
- •I3c. Cohort 3: Patients with RECIST 1.1-defined PD under anti-PD1/PD-L1 after initial objective response (CR or PR) or long-term benefit i.e. SD lasting at least 6 months as per RECIST V1.1
- •Note 1 : For patients treated with an anti-PD-1/ PD-L1 previously combined to another anti-cancer agents of any type (including but not limited to chemotherapy/ other immunotherapy/ biological -or targeted agents) theseagents must be stopped 2 weeks or 5\* t ½ whichever is shorter before C1D1 while anti-PD1 or anti PDL1 is continued according to Market Authorisation.
- •Note 2: Patients may have received a line of chemotherapy or any other standard anti-cancer agent after PD under anti-PD-1/PD-L1 but recurrence/progression under aPD-1/aPD-L1 y must have been documented ≤ 12 months before inclusion. Intercurrent chemotherapy or other standard agents must be stopped 2 weeks or 5\* t ½ whichever is shorter before C1D
排除标准
- •Patients eligible to curative treatment E
- •For refractory cohorts: patients eligible to standard treatment with documented proof of activity in the tumor type or to other therapeutic options (approved or investigational) with documented evidence of clinical activity.
- •For patients under chemotherapy /Immunotherapy/ biological- or targeted- or any other type of therapy + ICI before inclusion: Persistence of CTCAE ≥ Grade 2 toxicity due to prior combined agent (except alopecia (any grades), blood tests values according to inclusion criteria).
- •Patient with any history of CTCAE Grade 4 irAEs under anti-PD-1/PD-L1 treatment or any history of CTCAE Grade 3 requiring steroid treatment (\>10 mg/day prednisone or equivalent dose) for \>12 weeks or CTCAE Grade 2 pneumonitis regardless of steroid treatment.
- •History of severe (≥ Grade 3) allergic anaphylactic reactions to one of the components of NP137, standard ICI, premedication and/or any of their excipients.
- •Has known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, i.e., without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study treatment.
- •Has a known additional malignancy that is progressing or has required active treatment within the past 2 years.
- •Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g., breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded.
- •Prior therapy or needs to be treated with a forbidden concomitant/concurrent therapies/procedures including:
- •Any investigational agent or have used an investigational device. Note: Participants who have entered the follow-up phase of an investigational study may participate as long as it has been 2 weeks or 5\* ½ whichever is shorter after the last dose of the previous investigational agent.
研究组 & 干预措施
Stable Disease
Patients with a radiological documentation of SD according to RECIST V1.1 criteria following at least 12 weeks under standard PD-1/PD-L1 therapy. The initial evidence of SD is to be confirmed by a second assessment, no less than 4 weeks from the date of the first documented SD. Note : This treatment arm closed on 27/09/2024 due to non-feasibility.
干预措施: NP137
Stable Disease
Patients with a radiological documentation of SD according to RECIST V1.1 criteria following at least 12 weeks under standard PD-1/PD-L1 therapy. The initial evidence of SD is to be confirmed by a second assessment, no less than 4 weeks from the date of the first documented SD. Note : This treatment arm closed on 27/09/2024 due to non-feasibility.
干预措施: anti-PD-1/PD-L1
Primary refractory
Patients with documented radiological PD or short-term SD (\< 6months) according to RECIST V1.1 but with clinical benefit under PD-1/PD-L1 standard therapy.
干预措施: NP137
Primary refractory
Patients with documented radiological PD or short-term SD (\< 6months) according to RECIST V1.1 but with clinical benefit under PD-1/PD-L1 standard therapy.
干预措施: anti-PD-1/PD-L1
Secondary refractory
Patients with documented radiological PD following an initial Objective Response or long-term SD (i.e. ≥6 months) according to RECIST V1.1, with clinical benefit under standard PD-1/PD-L1.
干预措施: NP137
Secondary refractory
Patients with documented radiological PD following an initial Objective Response or long-term SD (i.e. ≥6 months) according to RECIST V1.1, with clinical benefit under standard PD-1/PD-L1.
干预措施: anti-PD-1/PD-L1
结局指标
主要结局
Objective Response Rate (ORR-12W)
时间窗: 12 weeks
Cohort 1 (SD): rate of patients with CR or PR according to RECIST V1.1 after the first 12 weeks of the NP137 as add on therapy.
Progression Free Rate at 12 weeks (PFR-12W)
时间窗: 12 weeks
Cohort 2 \& 3 (primary and secondary refractory refractory): defined as the proportion of patients without documented disease progression according to RECIST V1.1 or documented clinical disease progression after the first 12 weeks of the NP137 as add on therapy.
次要结局
- Time to objective response (ToR)(Every 12 weeks, up to 52 weeks)
- Duration of Response (DoR)(Every 12 weeks, up to 52 weeks)
- Objective Response Rate (ORR-12W)(12 weeks)
- Safety profile(from the date of first intake of study drug until 90 days after study drug discontinuation or at time of initiation of a new anti-cancer treatment)