Clinical trial NCT03228667: QUILT-3.055: A Study of Combination Immunotherapies in Patients Who Have Previously Received Treatment With Immune Checkpoint Inhibitors
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Non-Small Cell Lung Cancer
Small Cell Lung Cancer
Urothelial Carcinoma
Head and Neck Squamous Cell Carcinoma
Merkel Cell Carcinoma
Melanoma
Renal Cell Carcinoma
Gastric Cancer
Cervical Cancer
Hepatocellular Carcinoma
Microsatellite Instability
Mismatch Repair Deficiency
Colorectal Cancer
Keywords: Pembrolizumab
Nivolumab
Non-Small Cell Lung Cancer (NSCLC)
Immunotherapy
Interleukin-15
PD-1 Checkpoint Inhibitor
ALT-803
Atezolizumab
Avelumab
Small Cell Lung Cancer (SCLC)
Urothelial Carcinoma
Head and Neck Squamous Cell Carcinoma (HNSCC)
Merkel Cell Carcinoma (MCC)
Melanoma
Renal Cell Carcinoma (RCC)
Gastric Cancer
Cervical Cancer
Hepatocellular Carcinoma (HCC)
Microsatellite Instability-High (MSI-H)
PD-L1 Checkpoint Inhibitor
Mismatch Repair Deficient (dMMR) Solid Tumor Cancer
Colorectal Cancer (CRC)
Durvalumab
PD-L1 t-haNK
N-803
Keytruda
Opdivo
Imfinzi
Bavencio
Tecentriq
Lead sponsor: ImmunityBio, Inc.
Sponsor class: INDUSTRY
First posted: 2017-07-25
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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 outcomes:
measure: Objective Response Rate
timeFrame: 24 months
Secondary outcomes:
measure: Disease-specific Survival
timeFrame: 24 months
measure: Overall Survival
timeFrame: 24 months
measure: Time to Response
timeFrame: 24 months
measure: Duration of Response
timeFrame: 24 months
measure: Incidence of Adverse Events
timeFrame: 24 months
measure: Quality of life (QoL) - Assessed in cohorts 1-5 only.
timeFrame: 24 months
measure: Progression Free Survival
timeFrame: 24 months
Other outcomes:
Locations:
city: Anchorage
country: United States
facility: Alaska Clinical Research Center
state: Alaska
city: Hot Springs
country: United States
facility: Genesis Cancer Center
state: Arkansas
city: El Segundo
country: United States
facility: Chan Soon-Shiong Institute for Medicine
state: California
city: Fountain Valley
country: United States
facility: MemorialCare Health System
state: California
city: Glendale
country: United States
facility: Glendale Adventist Medical Center
state: California
city: Los Angeles
country: United States
facility: University of Southern California Norris Comprehensive Cancer Center
state: California
city: Rancho Mirage
country: United States
facility: Desert Hematology Oncology Medical Group, Inc.
state: California
city: Hollywood
country: United States
facility: Memorial Healthcare System
state: Florida
city: Miami
country: United States
facility: Miami Cancer Institute (Baptist Health South Florida)
state: Florida
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Lafayette
country: United States
facility: Horizon Oncology Associates
state: Indiana
city: Iowa City
country: United States
facility: University of Iowa Holden Comprehensive Cancer Center
state: Iowa
city: Lexington
country: United States
facility: Baptist Health - Lexington
state: Kentucky
city: Louisville
country: United States
facility: Baptist Health- Louisville
state: Kentucky
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Minneapolis
country: United States
facility: University of Minnesota - Masonic Cancer Center
state: Minnesota
city: Joplin
country: United States
facility: Mercy Research Joplin
state: Missouri
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Springfield
country: United States
facility: Mercy Clinic Cancer & Hematology - Chub O'Reilly Cancer Center
state: Missouri
city: Billings
country: United States
facility: St. Vincent Frontier Cancer Center (SCL)
state: Montana
city: Lebanon
country: United States
facility: Dartmouth-Hitchcock Medical Center
state: New Hampshire
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: Rochester
country: United States
facility: University of Rochester
state: New York
city: Cleveland
country: United States
facility: Cleveland Clinic - Main Site
state: Ohio
city: Oklahoma City
country: United States
facility: Mercy Clinic Oklahoma City
state: Oklahoma
city: Portland
country: United States
facility: Providence Portland Medical Center
state: Oregon
city: Gettysburg
country: United States
facility: Gettysburg/Hanover Cancer Centers
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Greenville
country: United States
facility: St. Francis Cancer Center/Bon Secours St. Francis Health System
state: South Carolina
city: Spartanburg
country: United States
facility: Spartanburg Medical Center
state: South Carolina
city: Sioux Falls
country: United States
facility: Sanford Clinical Research
state: South Dakota
city: Knoxville
country: United States
facility: University of Tennessee Medical Center
state: Tennessee
city: Houston
country: United States
facility: Oncology Consultants of Houston
state: Texas
city: Richmond
country: United States
facility: Bon Secours Richmond
state: Virginia
Study officials:
References: