Active, not recruiting
Phase 2
QUILT-3.055: A Study of Combination Immunotherapies in Patients Who Have Previously Received Treatment With Immune Checkpoint Inhibitors
Condition(s) studied
Non-Small Cell Lung CancerSmall Cell Lung CancerUrothelial CarcinomaHead and Neck Squamous Cell CarcinomaMerkel Cell CarcinomaMelanomaRenal Cell CarcinomaGastric CancerCervical CancerHepatocellular CarcinomaMicrosatellite InstabilityMismatch Repair DeficiencyColorectal Cancer
Investigational drug(s) / intervention(s)
N-803 + PembrolizumabN-803 + NivolumabN-803 + AtezolizumabN-803 + AvelumabN-803 + DurvalumabN-803 + Pembrolizumab + PD-L1 t-haNKN-803 + Nivolumab + PD-L1 t-haNKN-803 + Atezolizumab + PD-L1 t-haNKN-803 + Avelumab + PD-L1 t-haNKN-803 + Durvalumab + PD-L1 t-haNKN-803 + Docetaxel + PembrolizumabN-803 + Docetaxel + Nivolumab
N-803 + Pembrolizumab: Patients will receive 200 mg pembrolizumab as an intravenous infusion over 30 minutes every three weeks. Patients will receive 15 µg/kg N-803 administered by subcutaneous injection every three weeks.
N-803 + Nivolumab: Patients will receive 240 mg nivolumab as an intravenous infusion over 30 minutes every two weeks. Patients will receive 15 µg/kg N-803 administered by subcutaneous injection every three weeks.
N-803 + Atezolizumab: Patients will receive 1200 mg atezolizumab as an intravenous infusion over 60 minutes every 3 weeks; if the first infusion is tolerated, subsequent infusions may be given over 30 minutes. Patients will receive 15 µg/kg N-803 administered by subcutaneous injection every three weeks.
N-803 + Avelumab: Patients will receive 800 mg avelumab as an intravenous infusion over 60 minutes every 2 weeks. Patients will receive 15 µg/kg N-803 administered by subcutaneous injection every three weeks.
N-803 + Durvalumab: Patients will receive 10 mg/kg durvalumab as an intravenous infusion over 60 minutes every 2 weeks. Patients will receive 15 µg/kg N-803 administered by subcutaneous injection every three weeks.
N-803 + Pembrolizumab + PD-L1 t-haNK: Patients will receive 200 mg pembrolizumab as an intravenous infusion over 30 minutes every three weeks. Patients will receive 15 µg/kg N-803 administered by subcutaneous injection every three weeks. Patients will receive PD-L1 t-haNK administered IV over 30 minutes at \~2 x 10\^9 cells/dose weekly
N-803 + Nivolumab + PD-L1 t-haNK: Patients will receive 240 mg nivolumab as an intravenous infusion over 30 minutes every two weeks. Patients will receive 15 µg/kg N-803 administered by subcutaneous injection every three weeks. Patients will receive PD-L1 t-haNK administered IV over 30 minutes at \~2 x 10\^9 cells/dose weekly
N-803 + Atezolizumab + PD-L1 t-haNK: Patients will receive 1200 mg atezolizumab as an intravenous infusion over 60 minutes every 3 weeks; if the first infusion is tolerated, subsequent infusions may be given over 30 minutes. Patients will receive 15 µg/kg N-803 administered by subcutaneous injection every three weeks. Patients will receive PD-L1 t-haNK administered IV over 30 minutes at \~2 x 10\^9 cells/dose weekly
N-803 + Avelumab + PD-L1 t-haNK: Patients will receive 800 mg avelumab as an intravenous infusion over 60 minutes every 2 weeks. Patients will receive 15 µg/kg N-803 administered by subcutaneous injection every three weeks. Patients will receive PD-L1 t-haNK administered IV over 30 minutes at \~2 x 10\^9 cells/dose weekly
N-803 + Durvalumab + PD-L1 t-haNK: Patients will receive 10 mg/kg durvalumab as an intravenous infusion over 60 minutes every 2 weeks. Patients will receive 15 µg/kg N-803 administered by subcutaneous injection every three weeks. Patients will receive PD-L1 t-haNK administered IV over 30 minutes at \~2 x 10\^9 cells/dose weekly
N-803 + Docetaxel + Pembrolizumab: The study employs a 6-week cycle combination of: N-803 (1.2 mg flat dose SC), docetaxel (75 mg/m² IV - first 2 cycles only), and pembrolizumab (200 mg IV).
N-803 + Docetaxel + Nivolumab: The study employs a 6-week cycle combination of:N-803 (1.2 mg flat dose SC), docetaxel (75 mg/m² IV - first 2 cycles only), and nivolumab (240 mg IV). Nivolumab dosing may be increased to 480mg every four weeks as per the investigator's discretion.
Study summary
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.
Eligibility
INCLUSION CRITERIA (Cohort 6 only)
1. Age ≥ 18 years old.
2. Able to understand and provide a signed informed consent that fulfills the relevant IRB/IEC guidelines.
3. Pathologically confirmed stage IV NSCLC disease.
4. 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.
5. 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).
6. 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.
7. 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.
8. ECOG performance status of 0 to 2.
9. Measurable tumor lesions according to RECIST v1.1.
10. Ability to attend required study visits and return for adequate follow-up, as required by this protocol.
11. 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.
EXCLUSION CRITERIA (Cohort 6 only)
1. 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.
2. 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.
3. History of known active hepatitis B or C infection.
4. Active infection requiring antibiotic therapy.
5. History of or active inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis).
6. 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.
7. Inadequate organ function, evidenced by the following laboratory results:
1. Absolute lymphocyte count \< institutional ULN.
2. Absolute neutrophil count (ANC) \< 1,500 cells/mm3.
3. Platelet count \< 100,000 cells/mm3.
4. Total bilirubin greater than the upper limit of normal (ULN; unless the participant has documented Gilbert's syndrome).
5. Aspartate aminotransferase (AST \[SGOT\]) or ALT (SGPT) \> 1.5 × ULN.
6. Alkaline phosphatase (ALP) levels \> 2.5 × ULN.
7. Hemoglobin \< 9.0 g/dL.
8. 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 = \[(140 - age in years) × weight in kg × 1.00\] / \[72 × serum creatinine in mg/dL\]
8. Have any of following:
1. Cirrhosis at a level of Child-Pugh B (or worse);
2. Cirrhosis (any degree) and a history of hepatic encephalopathy; or
3. Clinically meaningful ascites resulting from cirrhosis. Clinically meaningful ascites is defined as ascites from cirrhosis requiring diuretics or paracentesis.
9. 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.
10. Assessed by the Investigator to be unable or unwilling to comply with the requirements of the protocol.
11. Pregnant and nursing women.
Primary outcome measure(s)
- ORR, defined as Investigator-assessed CR + PR per RECIST v1.1. — 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 — 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.
Trial sites (35)
| Facility | City | Region | Status |
| Alaska Clinical Research Center |
Anchorage |
Alaska |
|
| Genesis Cancer Center |
Hot Springs |
Arkansas |
|
| Chan Soon-Shiong Institute for Medicine |
El Segundo |
California |
|
| MemorialCare Health System |
Fountain Valley |
California |
|
| Glendale Adventist Medical Center |
Glendale |
California |
|
| University of Southern California Norris Comprehensive Cancer Center |
Los Angeles |
California |
|
| Desert Hematology Oncology Medical Group, Inc. |
Rancho Mirage |
California |
|
| Memorial Healthcare System |
Hollywood |
Florida |
|
| Miami Cancer Institute (Baptist Health South Florida) |
Miami |
Florida |
|
| University of Miami |
Miami |
Florida |
|
| Horizon Oncology Associates |
Lafayette |
Indiana |
|
| University of Iowa Holden Comprehensive Cancer Center |
Iowa City |
Iowa |
|
| Baptist Health - Lexington |
Lexington |
Kentucky |
|
| Baptist Health- Louisville |
Louisville |
Kentucky |
|
| Dana Farber Cancer Institute |
Boston |
Massachusetts |
|
| Henry Ford Hospital |
Detroit |
Michigan |
|
| University of Minnesota - Masonic Cancer Center |
Minneapolis |
Minnesota |
|
| Mercy Research Joplin |
Joplin |
Missouri |
|
| Mercy Clinic Cancer & Hematology - Chub O'Reilly Cancer Center |
Springfield |
Missouri |
|
| Washington University School of Medicine |
St Louis |
Missouri |
|
| St. Vincent Frontier Cancer Center (SCL) |
Billings |
Montana |
|
| Dartmouth-Hitchcock Medical Center |
Lebanon |
New Hampshire |
|
| Roswell Park Cancer Institute |
Buffalo |
New York |
|
| University of Rochester |
Rochester |
New York |
|
| Cleveland Clinic - Main Site |
Cleveland |
Ohio |
|
| Mercy Clinic Oklahoma City |
Oklahoma City |
Oklahoma |
|
| Providence Portland Medical Center |
Portland |
Oregon |
|
| Gettysburg/Hanover Cancer Centers |
Gettysburg |
Pennsylvania |
|
| Medical University of South Carolina |
Charleston |
South Carolina |
|
| St. Francis Cancer Center/Bon Secours St. Francis Health System |
Greenville |
South Carolina |
|
| Spartanburg Medical Center |
Spartanburg |
South Carolina |
|
| Sanford Clinical Research |
Sioux Falls |
South Dakota |
|
| University of Tennessee Medical Center |
Knoxville |
Tennessee |
|
| Oncology Consultants of Houston |
Houston |
Texas |
|
| Bon Secours Richmond |
Richmond |
Virginia |
|
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