QUILT-3.055: A Study of Combination Immunotherapies in Patients Who Have Previously Received Treatment With Immune Checkpoint Inhibitors
- Conditions
- Merkel Cell CarcinomaCervical CancerMismatch Repair DeficiencyMelanomaColorectal CancerUrothelial CarcinomaGastric CancerMicrosatellite InstabilityNon-Small Cell Lung CancerSmall Cell Lung Cancer
- Interventions
- Drug: N-803 + NivolumabDrug: N-803 + Nivolumab + PD-L1 t-haNKDrug: N-803 + Docetaxel + Nivolumab
- Registration Number
- NCT03228667
- Lead Sponsor
- ImmunityBio, Inc.
- Brief Summary
This Phase 2b, multicohort, open-label clinical trial (QUILT-3.055) evaluates combination immunotherapies in patients with various advanced solid tumors who have progressed following prior PD-1/PD-L1 checkpoint inhibitor therapy. The trial includes six cohorts:
Cohorts 1-4: Patients who progressed after an initial response (PR or CR) to prior PD-1/PD-L1 therapy, receiving combination therapy with N-803 and a PD-1/PD-L1 checkpoint inhibitor. (Closed to enrollment)
Cohort 5: Patients who progressed while receiving treatment in cohorts 1-4; they receive combination therapy with N-803, a PD-1/PD-L1 checkpoint inhibitor, and PD-L1 t-haNK cells.(Closed to enrollment)
Cohort 6A \& 6B: Patients with acquired resistance to prior PD-1/PD-L1 therapy; they receive combination therapy with N-803, docetaxel, and either pembrolizumab (6A) or nivolumab (6B).
Treatment is administered for up to two years or until disease progression, and participants are closely monitored for adverse events (AEs), including immune-related AEs, with specific dose modifications outlined. The primary endpoint is objective response rate (ORR) assessed by RECIST v1.1. The study uses Simon's two-stage design for cohorts 1-3 to determine the optimal dose and further assesses safety and efficacy endpoints for all cohorts.
- Detailed Description
Only Cohort 6 is recruiting.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 40
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Cohort 1 N-803 + Atezolizumab 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 Cohort 1 N-803 + Avelumab 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 Cohort 1 N-803 + Durvalumab 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 Cohort 4 N-803 + Atezolizumab 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. Cohort 4 N-803 + Avelumab 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. Cohort 4 N-803 + Durvalumab 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. Cohort 5 N-803 + Atezolizumab + PD-L1 t-haNK Patients that have experienced disease progression by Investigator-assessment per irRECIST while receiving treatment in Cohorts 1-4. Cohort 5 N-803 + Avelumab + PD-L1 t-haNK Patients that have experienced disease progression by Investigator-assessment per irRECIST while receiving treatment in Cohorts 1-4. Cohort 5 N-803 + Durvalumab + PD-L1 t-haNK Patients that have experienced disease progression by Investigator-assessment per irRECIST while receiving treatment in Cohorts 1-4. Cohort 1 N-803 + Pembrolizumab 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 Cohort 1 N-803 + Nivolumab 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 Cohort 2 N-803 + Pembrolizumab 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. Cohort 2 N-803 + Nivolumab 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. Cohort 3 N-803 + Pembrolizumab 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. Cohort 3 N-803 + Nivolumab 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. Cohort 4 N-803 + Pembrolizumab 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. Cohort 4 N-803 + Nivolumab 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. Cohort 5 N-803 + Pembrolizumab + PD-L1 t-haNK Patients that have experienced disease progression by Investigator-assessment per irRECIST while receiving treatment in Cohorts 1-4. Cohort 5 N-803 + Nivolumab + PD-L1 t-haNK Patients that have experienced disease progression by Investigator-assessment per irRECIST while receiving treatment in Cohorts 1-4. Cohort 6 N-803 + Docetaxel + Pembrolizumab 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). Cohort 6 N-803 + Docetaxel + Nivolumab 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).
- Primary Outcome Measures
Name Time Method Objective Response Rate 24 months Assess ORR, defined as Investigator-assessed CR + PR, per RECIST 1.1.
- Secondary Outcome Measures
Name Time Method Disease-specific Survival 24 months Assess time from first treatment to death resulting from cancer.
Overall Survival 24 months Assess time from first treatment to death resulting from any cause.
Time to Response 24 months Assess time to response
Duration of Response 24 months Assess duration of response
Incidence of Adverse Events 24 months Assess incidence of adverse events.
Quality of life (QoL) - Assessed in cohorts 1-5 only. 24 months Compare changes in QOL scores from baseline.
Progression Free Survival 24 months Assess time from first treatment to disease progression or death from any cause, whichever occurs first.
Trial Locations
- Locations (35)
Mercy Clinic Oklahoma City
🇺🇸Oklahoma City, Oklahoma, United States
Alaska Clinical Research Center
🇺🇸Anchorage, Alaska, United States
Genesis Cancer Center
🇺🇸Hot Springs, Arkansas, United States
Chan Soon-Shiong Institute for Medicine
🇺🇸El Segundo, California, United States
MemorialCare Health System
🇺🇸Fountain Valley, California, United States
Glendale Adventist Medical Center
🇺🇸Glendale, California, United States
University of Southern California Norris Comprehensive Cancer Center
🇺🇸Los Angeles, California, United States
Desert Hematology Oncology Medical Group, Inc.
🇺🇸Rancho Mirage, California, United States
Memorial Healthcare System
🇺🇸Hollywood, Florida, United States
Miami Cancer Institute (Baptist Health South Florida)
🇺🇸Miami, Florida, United States
University of Miami
🇺🇸Miami, Florida, United States
Horizon Oncology Associates
🇺🇸Lafayette, Indiana, United States
University of Iowa Holden Comprehensive Cancer Center
🇺🇸Iowa City, Iowa, United States
Baptist Health - Lexington
🇺🇸Lexington, Kentucky, United States
Baptist Health- Louisville
🇺🇸Louisville, Kentucky, United States
Dana Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Henry Ford Hospital
🇺🇸Detroit, Michigan, United States
University of Minnesota - Masonic Cancer Center
🇺🇸Minneapolis, Minnesota, United States
Mercy Research Joplin
🇺🇸Joplin, Missouri, United States
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
Mercy Clinic Cancer & Hematology - Chub O'Reilly Cancer Center
🇺🇸Springfield, Missouri, United States
St. Vincent Frontier Cancer Center (SCL)
🇺🇸Billings, Montana, United States
Dartmouth-Hitchcock Medical Center
🇺🇸Lebanon, New Hampshire, United States
Roswell Park Cancer Institute
🇺🇸Buffalo, New York, United States
University of Rochester
🇺🇸Rochester, New York, United States
Cleveland Clinic - Main Site
🇺🇸Cleveland, Ohio, United States
Providence Portland Medical Center
🇺🇸Portland, Oregon, United States
Gettysburg/Hanover Cancer Centers
🇺🇸Gettysburg, Pennsylvania, United States
Medical University of South Carolina
🇺🇸Charleston, South Carolina, United States
St. Francis Cancer Center/Bon Secours St. Francis Health System
🇺🇸Greenville, South Carolina, United States
Spartanburg Medical Center
🇺🇸Spartanburg, South Carolina, United States
Sanford Clinical Research
🇺🇸Sioux Falls, South Dakota, United States
University of Tennessee Medical Center
🇺🇸Knoxville, Tennessee, United States
Oncology Consultants of Houston
🇺🇸Houston, Texas, United States
Bon Secours Richmond
🇺🇸Richmond, Virginia, United States