QUILT-3.055: A Phase IIb, Multicohort, Open-Label Study of Combination Immunotherapies in Patients Who Have Previously Received Treatment With PD-1/PD-L1 Immune Checkpoint Inhibitors
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 40
- 试验地点
- 70
- 主要终点
- ORR, defined as Investigator-assessed CR + PR per RECIST v1.1.
研究概览
简要总结
QUILT-3.055 is a Phase 2b, open-label, multicohort study investigating combination immunotherapies in patients with advanced solid tumors who have previously been treated with PD-1/PD-L1 checkpoint inhibitors. The study aims to evaluate the safety and efficacy of NAI (nogapendekin alfa inbakicept) in combination with other agents like checkpoint inhibitors and cell therapies across various cancer types and treatment settings. The study includes multiple cohorts based on prior therapies and cancer types, with a focus on assessing overall response rate (ORR), overall survival (OS), and other measures of anti-tumor activity and immune response.
详细描述
All cohorts are closed to enrollment
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •(Cohort 6 only)
- •Age ≥ 18 years old.
- •Able to understand and provide a signed informed consent that fulfills the relevant IRB/IEC guidelines.
- •Pathologically confirmed stage IV NSCLC disease.
- •Have received exactly 1 anti-PD-1 or anti-PD-L1 therapy (either pembrolizumab or nivolumab) for advanced disease (stage IV or recurrent disease, or stage I-III disease in certain circumstances) outlined below. Anti-PD-1 or anti-PD-L1 therapy may have been given alone or in combination with other therapy.
- •a. For those participants who received neoadjuvant, adjuvant, and/or consolidation anti-PD-1 or anti-PD-L1 therapy for stage
- •I-III disease:
- •If they had disease progression within (≤) 365 days from initiation (cycle 1 day 1) of anti-PD-1 or anti-PD-L1 therapy, this counts as the single allowed anti-PD-1 or anti-PD-L1 therapy for advanced disease OR if they had disease progression more than (>) 365 days from initiation (cycle 1 day 1) of anti-PD-1 or anti-PD-L1 therapy, this is not considered anti-PD-1 or anti-PD-L1 therapy for advanced disease. These participants must have received anti-PD-1 or anti-PD-L1 therapy for stage IV or recurrent disease.
- •Have reported disease progression (in the opinion of the treating physician) more than (>) 84 days following initiation (cycle 1 day 1) of their most recent anti-PD-1 or anti-PD-L1 therapy (either pembrolizumab or nivolumab).
- •Participants who received anti-PD-1 or anti-PD-L1 therapy for stage IV or recurrent disease, must have had a best response of SD, PR or CR (in the opinion of the treating physician) on the anti- PD-1 or anti-PD-L1 therapy (either nivolumab or pembrolizumab) for stage IV or recurrent disease.
- •Participants with a known sensitizing mutation for which an - approved targeted therapy for NSCLC exists (e.g., EGFR, ALK, ROS1, BRAF, RET, NTRK, KRAS, HER2 and MET sensitizing mutations), must have previously received at least 1 of the approved therapy(s). Prior targeted therapy for participants with targetable alterations is allowed if all other eligibility criteria are also met.
- •ECOG performance status of 0 to
- •Measurable tumor lesions according to RECIST v1.
- •Ability to attend required study visits and return for adequate follow-up, as required by this protocol.
- •Agreement to practice effective contraception for female participants of child-bearing potential and non-sterile males. Female participants of child-bearing potential must agree to use effective contraception for up 7 months after completion of therapy, and non-sterile male participants must agree to use a condom for up to 7 months after treatment. Effective contraception includes surgical sterilization (eg, vasectomy, tubal ligation), orals, injectables, 2 forms of barrier methods (eg, condom, diaphragm) used with spermicide, intrauterine devices (IUDs), and hormonal therapy.
排除标准
- •(Cohort 6 only)
- •Systemic autoimmune disease currently requiring treatment (e.g., lupus erythematosus, rheumatoid arthritis, Addison's disease, or autoimmune disease associated with lymphoma). The participant must have been off treatment for 180 days.
- •History of organ transplant requiring immunosuppression; or history of pneumonitis or interstitial lung disease requiring treatment with systemic steroids; or a history of receiving systemic steroid therapy or any other immunosuppressive medication ≤ 3 days prior to study initiation. Daily steroid replacement therapy (eg, prednisone or hydrocortisone) and corticosteroids used to manage AEs are permitted.
- •History of known active hepatitis B or C infection.
- •Active infection requiring antibiotic therapy.
- •History of or active inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis).
- •Had major surgery within 28 days prior to study enrollment. Participants must have fully recovered from the effects of prior surgery in the opinion of the treating Investigator.
- •Inadequate organ function, evidenced by the following laboratory results:
- •Absolute lymphocyte count < institutional ULN.
- •Absolute neutrophil count (ANC) < 1,500 cells/mm
- •Platelet count < 100,000 cells/mm
- •Total bilirubin greater than the upper limit of normal (ULN; unless the participant has documented Gilbert's syndrome).
- •Aspartate aminotransferase (AST [SGOT]) or ALT (SGPT) > 1.5 × ULN.
- •Alkaline phosphatase (ALP) levels > 2.5 × ULN.
- •Hemoglobin < 9.0 g/dL.
- •Serum creatinine > 2.0 mg/dL or 177 μmol/L or creatinine clearance < 40 mL/min (using the Cockcroft-Gault formula below): Female = [(140 - age in years) × weight in kg × 0.85] / [72 × serum creatinine in mg/dL] Male = [(140 - age in years) × weight in kg × 1.00] / [72 × serum creatinine in mg/dL]
- •Have any of following:
- •Cirrhosis at a level of Child-Pugh B (or worse);
- •Cirrhosis (any degree) and a history of hepatic encephalopathy; or
- •Clinically meaningful ascites resulting from cirrhosis. Clinically meaningful ascites is defined as ascites from cirrhosis requiring diuretics or paracentesis.
- •Participation in an investigational drug study or history of receiving any investigational treatment within 30 days prior to the start of treatment on this study, except for hormone lowering therapy in participants with hormone-sensitive cancer.
- •Assessed by the Investigator to be unable or unwilling to comply with the requirements of the protocol.
- •Pregnant and nursing women.
研究组 & 干预措施
Cohort 1
Patients with any of the cancers listed below who have progressed on or after single-agent checkpoint inhibitor therapy after experiencing an initial complete response (CR) or partial response (PR) while taking a checkpoint inhibitor.
1a - Non-small cell lung cancer
1b - Small cell lung cancer
1c - Urothelial carcinoma
1d - Head and neck squamous cell carcinoma
1e - Merkel cell carcinoma
1f - Melanoma
1g - Renal cell carcinoma
1h - Gastric cancer
1i - Cervical cancer
1j - Hepatocellular carcinoma
1k - Microsatellite instability-high or mismatch repair deficient solid tumor cancer or colorectal cancer
干预措施: N-803 + Pembrolizumab (Drug)
Cohort 4
Patients who are currently receiving PD-1/PD-L1 checkpoint inhibitor therapy and have disease progression after experiencing stable disease (SD) for at least 6 months during their previous treatment with PD-1/PD-L1 checkpoint inhibitor therapy.
干预措施: N-803 + Nivolumab (Drug)
Cohort 1
Patients with any of the cancers listed below who have progressed on or after single-agent checkpoint inhibitor therapy after experiencing an initial complete response (CR) or partial response (PR) while taking a checkpoint inhibitor.
1a - Non-small cell lung cancer
1b - Small cell lung cancer
1c - Urothelial carcinoma
1d - Head and neck squamous cell carcinoma
1e - Merkel cell carcinoma
1f - Melanoma
1g - Renal cell carcinoma
1h - Gastric cancer
1i - Cervical cancer
1j - Hepatocellular carcinoma
1k - Microsatellite instability-high or mismatch repair deficient solid tumor cancer or colorectal cancer
干预措施: N-803 + Nivolumab (Drug)
Cohort 1
Patients with any of the cancers listed below who have progressed on or after single-agent checkpoint inhibitor therapy after experiencing an initial complete response (CR) or partial response (PR) while taking a checkpoint inhibitor.
1a - Non-small cell lung cancer
1b - Small cell lung cancer
1c - Urothelial carcinoma
1d - Head and neck squamous cell carcinoma
1e - Merkel cell carcinoma
1f - Melanoma
1g - Renal cell carcinoma
1h - Gastric cancer
1i - Cervical cancer
1j - Hepatocellular carcinoma
1k - Microsatellite instability-high or mismatch repair deficient solid tumor cancer or colorectal cancer
干预措施: N-803 + Atezolizumab (Drug)
Cohort 1
Patients with any of the cancers listed below who have progressed on or after single-agent checkpoint inhibitor therapy after experiencing an initial complete response (CR) or partial response (PR) while taking a checkpoint inhibitor.
1a - Non-small cell lung cancer
1b - Small cell lung cancer
1c - Urothelial carcinoma
1d - Head and neck squamous cell carcinoma
1e - Merkel cell carcinoma
1f - Melanoma
1g - Renal cell carcinoma
1h - Gastric cancer
1i - Cervical cancer
1j - Hepatocellular carcinoma
1k - Microsatellite instability-high or mismatch repair deficient solid tumor cancer or colorectal cancer
干预措施: N-803 + Avelumab (Drug)
Cohort 1
Patients with any of the cancers listed below who have progressed on or after single-agent checkpoint inhibitor therapy after experiencing an initial complete response (CR) or partial response (PR) while taking a checkpoint inhibitor.
1a - Non-small cell lung cancer
1b - Small cell lung cancer
1c - Urothelial carcinoma
1d - Head and neck squamous cell carcinoma
1e - Merkel cell carcinoma
1f - Melanoma
1g - Renal cell carcinoma
1h - Gastric cancer
1i - Cervical cancer
1j - Hepatocellular carcinoma
1k - Microsatellite instability-high or mismatch repair deficient solid tumor cancer or colorectal cancer
干预措施: N-803 + Durvalumab (Drug)
Cohort 2
Patients with NSCLC whose tumors have high PD-L1 expression (TPS ≥ 50%) and who relapsed on a PD-1 checkpoint inhibitor after experiencing an initial CR or PR when they received checkpoint inhibitor as a single-agent for first-line treatment.
干预措施: N-803 + Pembrolizumab (Drug)
Cohort 2
Patients with NSCLC whose tumors have high PD-L1 expression (TPS ≥ 50%) and who relapsed on a PD-1 checkpoint inhibitor after experiencing an initial CR or PR when they received checkpoint inhibitor as a single-agent for first-line treatment.
干预措施: N-803 + Nivolumab (Drug)
Cohort 3
Patients with NSCLC who had an initial CR or PR but subsequently relapsed on maintenance PD-1 checkpoint inhibitor therapy when they initially received checkpoint inhibitor therapy in combination with chemotherapy as first-line treatment.
干预措施: N-803 + Pembrolizumab (Drug)
Cohort 3
Patients with NSCLC who had an initial CR or PR but subsequently relapsed on maintenance PD-1 checkpoint inhibitor therapy when they initially received checkpoint inhibitor therapy in combination with chemotherapy as first-line treatment.
干预措施: N-803 + Nivolumab (Drug)
Cohort 4
Patients who are currently receiving PD-1/PD-L1 checkpoint inhibitor therapy and have disease progression after experiencing stable disease (SD) for at least 6 months during their previous treatment with PD-1/PD-L1 checkpoint inhibitor therapy.
干预措施: N-803 + Pembrolizumab (Drug)
Cohort 4
Patients who are currently receiving PD-1/PD-L1 checkpoint inhibitor therapy and have disease progression after experiencing stable disease (SD) for at least 6 months during their previous treatment with PD-1/PD-L1 checkpoint inhibitor therapy.
干预措施: N-803 + Atezolizumab (Drug)
Cohort 4
Patients who are currently receiving PD-1/PD-L1 checkpoint inhibitor therapy and have disease progression after experiencing stable disease (SD) for at least 6 months during their previous treatment with PD-1/PD-L1 checkpoint inhibitor therapy.
干预措施: N-803 + Avelumab (Drug)
Cohort 4
Patients who are currently receiving PD-1/PD-L1 checkpoint inhibitor therapy and have disease progression after experiencing stable disease (SD) for at least 6 months during their previous treatment with PD-1/PD-L1 checkpoint inhibitor therapy.
干预措施: N-803 + Durvalumab (Drug)
Cohort 5
Patients that have experienced disease progression by Investigator-assessment per irRECIST while receiving treatment in Cohorts 1-4.
干预措施: N-803 + Pembrolizumab + PD-L1 t-haNK (Drug)
Cohort 5
Patients that have experienced disease progression by Investigator-assessment per irRECIST while receiving treatment in Cohorts 1-4.
干预措施: N-803 + Nivolumab + PD-L1 t-haNK (Drug)
Cohort 5
Patients that have experienced disease progression by Investigator-assessment per irRECIST while receiving treatment in Cohorts 1-4.
干预措施: N-803 + Atezolizumab + PD-L1 t-haNK (Drug)
Cohort 5
Patients that have experienced disease progression by Investigator-assessment per irRECIST while receiving treatment in Cohorts 1-4.
干预措施: N-803 + Avelumab + PD-L1 t-haNK (Drug)
Cohort 5
Patients that have experienced disease progression by Investigator-assessment per irRECIST while receiving treatment in Cohorts 1-4.
干预措施: N-803 + Durvalumab + PD-L1 t-haNK (Drug)
Cohort 6
Patients who have progressed after an initial response (CR or PR) to a PD-1/PD-L1 checkpoint inhibitor but now exhibit acquired resistance. They have received exactly one line of anti-PD-1 or anti-PD-L1 therapy (either pembrolizumab or nivolumab) for advanced NSCLC (Stage IV or recurrent).
干预措施: N-803 + Docetaxel + Pembrolizumab (Drug)
Cohort 6
Patients who have progressed after an initial response (CR or PR) to a PD-1/PD-L1 checkpoint inhibitor but now exhibit acquired resistance. They have received exactly one line of anti-PD-1 or anti-PD-L1 therapy (either pembrolizumab or nivolumab) for advanced NSCLC (Stage IV or recurrent).
干预措施: N-803 + Docetaxel + Nivolumab (Drug)
结局指标
主要结局
ORR, defined as Investigator-assessed CR + PR per RECIST v1.1.
时间窗: Evaluated from the first dose of study drug and repeated at each scheduled disease-assessment visit for up to 24 months (or until progression/death), with the time-to-response summarized using Kaplan-Meier methods
ORR reflects tumor shrinkage and is the key measure of antitumor activity.
Prolongation of OS with NAI therapy by ALC response, where: - OS is defined as the time from first study drug administration to death resulting from any cause. - ALC response is defined as achievement or maintenance of an on-treatment ALC ≥ 1,000 cells/μ
时间窗: Measured from the date of the first study-drug administration to the date of death (any cause) and followed for up to 24 months after the last dose (or until death), allowing the correlation with on-treatment ALC changes
OS is the gold-standard efficacy endpoint; the protocol explores whether an ALC rise predicts a survival benefit.
次要结局
- ALC response to NAI therapy(From the date of first study-drug administration until the earlier of death or the planned end of follow-up, assessed up to 24 months.)
- Prolongation of therapy(From the date of first study-drug administration until the earlier of death or the planned end of study follow-up, assessed up to 24 months after the last dose of study drug.)
- Overall survival (OS) for all patients and subgroups(From the date of first study-drug administration until the earlier of death or the planned end of study follow-up, assessed up to 24 months after the last dose of study drug.)
- Disease-specific survival (DSS)(From the date of first study-drug administration until the earlier of death or the planned end of study follow-up, assessed up to 24 months after the last dose of study drug.)
- Progression-free survival (PFS)(From the date of first study-drug administration until the earlier of death or the planned end of study follow-up, assessed up to 24 months after the last dose of study drug.)
- Time to response(From the date of first study-drug administration until the earlier of death or the planned end of study follow-up, assessed up to 24 months after the last dose of study drug.)
- Duration of response (DoR)(From the date of first study-drug administration until the earlier of death or the planned end of study follow-up, assessed up to 24 months after the last dose of study drug.)
- Disease Control Rate (DCR):(Assessed at the end of each 6-week cycle (each cycle = 42 days) through 2 years (up to Cycle 17))
- Quality of life (QoL) - Assessed in cohorts 1-5 only.(From the date of first study-drug administration until the earlier of death or the planned end of study follow-up, assessed up to 24 months after the last dose of study drug.)
- Physical examinations(Baseline (screening), Day 1 (first dose), and prior to every subsequent NAI dose (e.g., every 2 weeks), then at each post-treatment safety visit (Week 12, Week 24, Week 36, Week 48, and at end-of-study visit))