QUILT-3.063: A Study of N-803, haNK and Avelumab in Patients With Merkel Cell Carcinoma That Has Progressed After Checkpoint Therapy

NCT03853317 | Terminated Phase 2 Results FDA Drug

• 1 other identifier: QUILT-3.063
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 5

Brief Summary

Phase 2, single-arm study to evaluate combination therapy of avelumab, haNK and N-803 in patients with Merkel Cell Carcinoma who have progressed on or after checkpoint inhibitor therapy as assessed by ORR. Patients will receive treatment for a maximum of two years.

Conditions

Merkel Cell Carcinoma

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Adverse Events

  The safety of the combination treatment of avelumab, haNK, and N-803 in subjects with MCC that has progressed on or after checkpoint inhibitor therapy

  30 days after last dose, approximately 1 year 7 months

• Objective Response Rate

  Percent of subjects with confirmed complete Response (CR; disappearance of all target lesions) or partial response (PR; \>=30% decrease in the sum of the longest diameter of target lesions) by RECIST v1.1

  approximately 1 year 7 months

Secondary Outcomes (9)

• Overall Response Rate by iRECIST (Percent of Subjects With Confirmed Complete or Partial Overall Response)

  Up to 2 years

• Progression Free Survival

  Up to 2 years

• Progression Free Survival

  Up to 2 years

• Overall Survival

  Up to 2 years

• Disease-Specific Survival

  Up to 2 years

Study Arms (1)

Treatment with avelumab, haNK™ and N-803

EXPERIMENTAL

The primary objective is to determine the efficacy of the combination treatment of avelumab, haNK, and N-803 in subjects with MCC that has progressed on or after checkpoint inhibitor therapy by objective response rate (ORR) using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)

Biological: Avelumab; Biological: N-803; Biological: haNK™

Interventions

Avelumab BIOLOGICAL

For the treatment of adults and pediatric patients 12 years and older with Metastatic Merkel Cell Carcinoma (MCC).

Also known as: (BAVENCIO® injection, for intravenous [IV] use)

Treatment with avelumab, haNK™ and N-803

N-803 BIOLOGICAL

Recombinant human super agonist interleukin-15 (IL-15) complex

Also known as: also known as IL-15N72D:IL-15RαSu/IgG1 Fc complex]), ALT-803

Treatment with avelumab, haNK™ and N-803

haNK™ BIOLOGICAL

haNK™ for Infusion is a human, allogeneic, NK cell line that has been engineered to produce endogenous, intracellularly retained IL-2 and to express CD16, the high-affinity (158V) Fc gamma receptor (FcγRIIIa/CD16a).

Also known as: NK-92 [CD16.158V, ER IL-2], (haNK™ for Infusion)

Treatment with avelumab, haNK™ and N-803

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 on day of signing informed consent.
• Able to understand and provide a signed informed consent that fulfills the relevant IRB or IEC guidelines.
• Histologically-confirmed metastatic MCC that has progressed during treatment or within 6 months after completing treatment with single-agent avelumab or pembrolizumab therapy, as per FDA indication.
• ECOG performance status of 0 to 2.
• Have at least 1 measurable lesion of ≥ 1.0 cm.
• Must have a recent FFPE tumor biopsy specimen following the conclusion of the most recent anticancer treatment and be willing to release the specimen for exploratory tumor molecular profiling. If an historic specimen is not available, the subject must be willing to undergo a biopsy during the screening period, if considered safe by the Investigator. If safety concerns preclude collection of a biopsy during the screening period, a tumor biopsy specimen collected prior to the conclusion of the most recent anticancer treatment may be used.
• Must be willing to provide blood samples for exploratory analyses.
• Must be willing to provide a tumor biopsy specimen 8 weeks after the start of treatment for exploratory analyses, if considered safe by the Investigator.
• Ability to attend required study visits and return for adequate follow-up, as required by this protocol.
• Agreement to practice effective contraception for female subjects of child-bearing potential and non-sterile males. Female subjects of child-bearing potential must agree to use effective contraception for up to 1 year after completion of therapy, and non-sterile male subjects must agree to use a condom for up to 4 months after treatment. Effective contraception includes surgical sterilization (eg, vasectomy, tubal ligation), two forms of barrier methods (eg, condom, diaphragm) used with spermicide, intrauterine devices (IUDs), and abstinence.

You may not qualify if:

• Serious uncontrolled concomitant disease that would contraindicate the use of the investigational drug used in this study or that would put the subject at high risk for treatment-related complications.
• Systemic autoimmune disease (eg, lupus erythematosus, rheumatoid arthritis, \[subjects with mild rheumatoid arthritis that aren't currently receiving treatment for their disease are eligible for enrollment\], Addison's disease, or autoimmune disease associated with lymphoma).
• History of organ transplant requiring immunosuppression.
• History of or active inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis).
• Inadequate organ function, evidenced by the following laboratory results:
• ANC \< 900 cells/mm3.
• Platelet count \< 75,000 cells/mm3
• Total bilirubin greater than twice the ULN (unless the subject has documented Gilbert's syndrome).
• AST (SGOT) or ALT (SGPT) \> 2.5 × ULN (\> 5 × ULN in subjects with liver metastases).
• ALP levels \> 2.5 × ULN (\> 5 × ULN in subjects with liver metastases, or \>10 × ULN in subjects with bone metastases).
• Uncontrolled hypertension (systolic \> 160 mm Hg and/or diastolic \> 110 mm Hg) or clinically significant (ie, active) cardiovascular disease, cerebrovascular accident/stroke, or myocardial infarction within 6 months prior to first study medication; unstable angina; congestive heart failure of New York Heart Association grade 2 or higher; or serious cardiac arrhythmia requiring medication.
• Dyspnea at rest due to complications of advanced malignancy or other disease requiring continuous oxygen therapy.
• Current chronic daily treatment (continuous for \> 3 months) with systemic corticosteroids (dose equivalent to or greater than 10 mg/day methylprednisolone), excluding inhaled steroids. Short-term steroid use to prevent IV contrast allergic reaction or anaphylaxis in subjects who have known contrast allergies is allowed.
• Known hypersensitivity to any component of the study medication(s), including anaphylactic reaction to sulfur-containing medications.
• Subjects taking any medication(s) (herbal or prescribed) known to have an adverse drug reaction with any of the study medications.

Sponsors & Collaborators

• ImmunityBio, Inc.: lead

Study Sites (5)

University of California San Francisco

San Francisco, California, 94143, United States

Location

University of Miami, Sylvester Comprehensive Cancer Center

Miami, Florida, 33136, United States

Location

Miami Cancer Institute - Baptist Health

Miami, Florida, 33176, United States

Location

Washington University School of Medicine in St. Louis

St Louis, Missouri, 63110, United States

Location

Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

Location

MeSH Terms

Conditions

Carcinoma, Merkel Cell

Interventions

avelumab; ALT-803

Condition Hierarchy (Ancestors)

Polyomavirus Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections; Carcinoma, Neuroendocrine; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Results Point of Contact

• Title: Sandeep Bobby Reddy, Chief Medical Officer
• Organization: ImmunityBio

Bobby.Reddy@immunitybio.com

855-797-9277

Study Officials

• Bobby Reddy, MD

  ImmunityBio, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 14, 2019
• First Posted: February 25, 2019
• Study Start: February 19, 2020
• Primary Completion: September 29, 2021
• Study Completion: September 19, 2022
• Last Updated: August 9, 2024
• Results First Posted: August 9, 2024

Record last verified: 2024-08

Locations

US (5)