QUILT-3.055: A Study of Combination Immunotherapies in Patients Who Have Previously Received Treatment With Immune Checkpoint Inhibitors

NCT03228667 | Active Not Recruiting Phase 2 FDA Drug

• 1 other identifier: CA-ALT-803-02-17
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 35

Brief 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.

Conditions

Small Cell Lung Cancer; Urothelial Carcinoma; Merkel Cell Carcinoma; Hepatocellular Carcinoma; Microsatellite Instability; Mismatch Repair Deficiency; Non-Small Cell Lung Cancer; Head and Neck Squamous Cell Carcinoma; Melanoma; Renal Cell Carcinoma; Gastric Cancer; Cervical Cancer; 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

Outcome Measures

Primary Outcomes (2)

• ORR, defined as Investigator-assessed CR + PR per RECIST v1.1.

  ORR reflects tumor shrinkage and is the key measure of antitumor activity.

  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

• 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

  OS is the gold-standard efficacy endpoint; the protocol explores whether an ALC rise predicts a survival benefit.

  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

Secondary Outcomes (10)

• 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.

Other Outcomes (19)

• Incidence of TEAEs and SAEs

  Captured continuously from the first dose of study drug and monitored at every study visit throughout the treatment period and the post-treatment follow-up phase (until study closure, typically up to ~24 months after the last dose).

• Laboratory tests

  Baseline, Day 1, on-treatment (prior to each dose; every 2 weeks), and at each post-treatment safety visit (Week 12, Week 24, Week 36, Week 48, and end-of-study)

• Vital signs

  Baseline, Day 1, before each NAI infusion (typically every 2 weeks), and at all scheduled safety follow-up visits (Week 12, Week 24, Week 36, Week 48, and final study visit)

Study Arms (6)

Cohort 1

OTHER

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

Drug: N-803 + Pembrolizumab; Drug: N-803 + Nivolumab; Drug: N-803 + Atezolizumab; Drug: N-803 + Avelumab; Drug: N-803 + Durvalumab

Cohort 2

OTHER

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.

Drug: N-803 + Pembrolizumab; Drug: N-803 + Nivolumab

Cohort 3

OTHER

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.

Drug: N-803 + Pembrolizumab; Drug: N-803 + Nivolumab

Cohort 4

EXPERIMENTAL

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.

Drug: N-803 + Pembrolizumab; Drug: N-803 + Nivolumab; Drug: N-803 + Atezolizumab; Drug: N-803 + Avelumab; Drug: N-803 + Durvalumab

Cohort 5

EXPERIMENTAL

Patients that have experienced disease progression by Investigator-assessment per irRECIST while receiving treatment in Cohorts 1-4.

Drug: N-803 + Pembrolizumab + PD-L1 t-haNK; Drug: N-803 + Nivolumab + PD-L1 t-haNK; Drug: N-803 + Atezolizumab + PD-L1 t-haNK; Drug: N-803 + Avelumab + PD-L1 t-haNK; Drug: N-803 + Durvalumab + PD-L1 t-haNK

Cohort 6

EXPERIMENTAL

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).

Drug: N-803 + Docetaxel + Pembrolizumab; Drug: N-803 + Docetaxel + Nivolumab

Interventions

N-803 + Nivolumab + PD-L1 t-haNK DRUG

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

Cohort 5

N-803 + Atezolizumab + PD-L1 t-haNK DRUG

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

Cohort 5

N-803 + Avelumab + PD-L1 t-haNK DRUG

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

Cohort 5

N-803 + Pembrolizumab DRUG

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.

Cohort 1; Cohort 2; Cohort 3; Cohort 4

N-803 + Nivolumab DRUG

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.

Cohort 1; Cohort 2; Cohort 3; Cohort 4

N-803 + Atezolizumab DRUG

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.

Cohort 1; Cohort 4

N-803 + Avelumab DRUG

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.

Cohort 1; Cohort 4

N-803 + Durvalumab DRUG

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.

Cohort 1; Cohort 4

N-803 + Pembrolizumab + PD-L1 t-haNK DRUG

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

Cohort 5

N-803 + Durvalumab + PD-L1 t-haNK DRUG

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

Cohort 5

N-803 + Docetaxel + Pembrolizumab DRUG

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).

Cohort 6

N-803 + Docetaxel + Nivolumab DRUG

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.

Cohort 6

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 2.
• Measurable tumor lesions according to RECIST v1.1.
• 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.

You may not qualify if:

• 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/mm3.
• Platelet count \< 100,000 cells/mm3.
• 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 = \[(140 - age in years) × weight in kg × 1.00\] / \[72 × serum creatinine in mg/dL\]

Sponsors & Collaborators

• ImmunityBio, Inc.: lead

Study Sites (35)

Alaska Clinical Research Center

Anchorage, Alaska, 99530, United States

Location

Genesis Cancer Center

Hot Springs, Arkansas, 71913, United States

Location

Chan Soon-Shiong Institute for Medicine

El Segundo, California, 90245, United States

Location

MemorialCare Health System

Fountain Valley, California, 37846, United States

Location

Glendale Adventist Medical Center

Glendale, California, 91206, United States

Location

University of Southern California Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

Desert Hematology Oncology Medical Group, Inc.

Rancho Mirage, California, 92270, United States

Location

Memorial Healthcare System

Hollywood, Florida, 33021, United States

Location

Miami Cancer Institute (Baptist Health South Florida)

Miami, Florida, 33176, United States

Location

University of Miami

Miami, Florida, 33180, United States

Location

Horizon Oncology Associates

Lafayette, Indiana, 47905, United States

Location

University of Iowa Holden Comprehensive Cancer Center

Iowa City, Iowa, 52242, United States

Location

Baptist Health - Lexington

Lexington, Kentucky, 40503, United States

Location

Baptist Health- Louisville

Louisville, Kentucky, 40207, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Henry Ford Hospital

Detroit, Michigan, 48202, United States

Location

University of Minnesota - Masonic Cancer Center

Minneapolis, Minnesota, 55455, United States

Location

Mercy Research Joplin

Joplin, Missouri, 64804, United States

Location

Mercy Clinic Cancer & Hematology - Chub O'Reilly Cancer Center

Springfield, Missouri, 65804, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

St. Vincent Frontier Cancer Center (SCL)

Billings, Montana, 59102, United States

Location

Dartmouth-Hitchcock Medical Center

Lebanon, New Hampshire, 03756, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

University of Rochester

Rochester, New York, 14642, United States

Location

Cleveland Clinic - Main Site

Cleveland, Ohio, 44195, United States

Location

Mercy Clinic Oklahoma City

Oklahoma City, Oklahoma, 73120, United States

Location

Providence Portland Medical Center

Portland, Oregon, 97213, United States

Location

Gettysburg/Hanover Cancer Centers

Gettysburg, Pennsylvania, 17325, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

St. Francis Cancer Center/Bon Secours St. Francis Health System

Greenville, South Carolina, 29607, United States

Location

Spartanburg Medical Center

Spartanburg, South Carolina, 29303, United States

Location

Sanford Clinical Research

Sioux Falls, South Dakota, 57104, United States

Location

University of Tennessee Medical Center

Knoxville, Tennessee, 37920, United States

Location

Oncology Consultants of Houston

Houston, Texas, 77024, United States

Location

Bon Secours Richmond

Richmond, Virginia, 23114, United States

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Small Cell Lung Carcinoma; Carcinoma, Transitional Cell; Squamous Cell Carcinoma of Head and Neck; Carcinoma, Merkel Cell; Melanoma; Carcinoma, Renal Cell; Stomach Neoplasms; Uterine Cervical Neoplasms; Carcinoma, Hepatocellular; Microsatellite Instability; Turcot syndrome; Colorectal Neoplasms

Interventions

ALT-803; pembrolizumab; Nivolumab; atezolizumab; avelumab; durvalumab; Docetaxel

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Carcinoma, Squamous Cell; Head and Neck Neoplasms; Polyomavirus Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections; Carcinoma, Neuroendocrine; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Adenocarcinoma; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Skin Diseases; Skin and Connective Tissue Diseases; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Uterine Neoplasms; Genital Neoplasms, Female; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Genital Diseases; Liver Neoplasms; Liver Diseases; Genomic Instability; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Intestinal Neoplasms; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 21, 2017
• First Posted: July 25, 2017
• Study Start: December 11, 2018
• Primary Completion (Estimated): August 31, 2029
• Study Completion (Estimated): December 31, 2030
• Last Updated: January 14, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (35)