Trial Title:
Memory-Like Natural Killer Cells With Nivolumab and Relatlimab in Advanced or Metastatic Melanoma After Progression on Checkpoint Inhibitors
NCT ID:
NCT05629546
Condition:
Advanced Melanoma
Metastatic Melanoma
Conditions: Official terms:
Melanoma
Nivolumab
Conditions: Keywords:
advanced melanoma
metastatic melanoma
checkpoint inhibitor resistant melanoma
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Parallel Assignment
Intervention model description:
Enrollment will occur in parallel into arms 1 and 2, but sequence of enrollment will be
staggered for the first 3 patients, with sequential patients being enrolled upon the
previous patient completing 30 days of observation. Approximately 11 allogeneic donors
will also be enrolled for subjects in Arm 2.
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Biological
Intervention name:
Cytokine-induced memory-like natural killer cells
Description:
Cell product processing is performed at the Siteman Cancer Center Biological Therapy Core
Facility (BTCF).
Arm group label:
Arm 1: Autologous: Memory-like natural killer cells + nivolumab + relatilimab
Arm group label:
Arm 2: Allogeneic: Memory-like natural killer cells + nivolumab + relatilimab
Other name:
ML NK cells
Other name:
CIML
Intervention type:
Biological
Intervention name:
Relatilmab
Description:
Standard of care
Arm group label:
Arm 1: Autologous: Memory-like natural killer cells + nivolumab + relatilimab
Arm group label:
Arm 2: Allogeneic: Memory-like natural killer cells + nivolumab + relatilimab
Other name:
Opdualag
Intervention type:
Biological
Intervention name:
Nivolumab
Description:
Standard of care
Arm group label:
Arm 1: Autologous: Memory-like natural killer cells + nivolumab + relatilimab
Arm group label:
Arm 2: Allogeneic: Memory-like natural killer cells + nivolumab + relatilimab
Summary:
This is a Phase 1 open-label, study designed to characterize the safety, tolerability,
and preliminary anti-tumor activity of memory-like natural killer cells (ML NK) in
combination with nivolumab and relatlimab in subjects with advanced and/or metastatic
melanoma. There will be two arms to test the variables of ML NK cell source. ML NK cells
from an autologous source will be used for Arm 1, and ML NK cells from an allogeneic
source will be used for Arm 2. The investigators hypothesize that ML NK cells from either
an autologous source or allogeneic source are safe and tolerable in subjects with
advanced and/or metastatic melanoma.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Diagnosis of histologically confirmed advanced or metastatic melanoma that has
progressed after at least 12 weeks or a minimum of 2 doses of treatment with a
standard of care PD1/PDL1 containing therapy (nivolumab, pembrolizumab,
atezolizumab, or durvalumab) as their last treatment regimen.
- Age: ≥18 years of age
- Have an Eastern Cooperative Oncology Group Performance Status (ECOG) ≤ 2 at
screening Form Arm 1 only: Patients must meet the eligibility criteria to undergo
apheresis to obtain autlogous NK cells.
- For Arm 2 only: Patient must have an available allogeneic NK cell donor who meets
the eligibility criteria.
- Adequate organ function as defined below:
- Total bilirubin < 2 mg/dL
- AST(SGOT)/ALT(SGPT) < 3.0 x ULN
- Creatinine within normal institutional limits OR creatinine clearance > 40
mL/min/1.73 m^2 by Cockcroft-Gault Formula
- Oxygen saturation ≥ 90% on room air
- Ejection fraction ≥ 45%
- Patients with a prior history of symptomatic CNS metastases must have received
treatment and be neurologically stable for at least for 4 weeks and off anti-seizure
medication and steroids for 7 days prior to initiation of LDC.
- Able to be off corticosteroids and any other immune suppressive medications for at
least 14 days prior to apheresis or lymphodepletion and continuing until 30 days
after the infusion of the ML NK cells. However, use of physiological dosing of
corticosteroids (defined as ≤15mg prednisone or equivalent) is permitted if deemed
medically necessary.
- Women of childbearing potential must have a negative pregnancy test within 21 days
prior to study registration. Female and male patients (along with their female
partners) must agree to use two forms of acceptable contraception, including one
barrier method, throughout participation in the study and for at least 5 months
after the last dose of relatlimab.
- Life expectancy >12 weeks
- Ability to understand and willingness to sign an IRB approved written informed
consent document
Exclusion Criteria:
- Active autoimmune disorder requiring immunosuppression (physiologic steroids defined
as ≤15mg prednisone or equivalent are acceptable).
- Prior history of an immune-related Grade 3 or 4 AE attributed to prior cancer
immunotherapy (other than endocrinopathy managed with either replacement therapy or
asymptomatic elevation of serum amylase or lipase) that resulted in permanent
discontinuation of the prior immunotherapeutic agent.
- Patients with Grade ≤2 irAE who have not completely recovered from irAE (i.e. have
residual toxicities >Grade 1) related to prior cancer immunotherapy (other than
endocrinopathy management with replacement therapy or stable vitiligo). Patients
treated with corticosteroids for irAE must demonstrate absence of related signs or
symptoms for ≥7 days following discontinuation of corticosteroids.
- Leptomeningeal disease, carcinomatous meningitis, or symptomatic CNS metastases.
Patients with asymptomatic brain metastasis with no pending intervention needed, or
patients with treated CNS disease and stable for at least 4 weeks and off
anti-seizure medication and steroids for 7 days prior to initiation of LDC are
eligible.
- Has previously received and progressed on prior nivolumab and relatlimab therapy.
- Known hypersensitivity to one or more of the study agents.
- Comorbidities and any conditions, that in the opinion of the investigator, that put
the subject at unacceptable risk for study therapy or prevent the participant from
consenting or participating in the study.
- Uncontrolled and active systemic infections, including but not limited to HIV,
Hepatitis B or C infection.
- Uncontrolled angina, severe uncontrolled ventricular arrhythmias, or EKG suggestive
of acute ischemia or active conduction system abnormalities.
- New progressive pulmonary infiltrates concerning for new or uncontrolled infectious
process. Infiltrates attributed to infection must be stable/ improving after 1 week
of appropriate therapy (4 weeks for presumed or proven fungal infections).
- Received any investigational drugs within the 14 days prior to the first dose of
fludarabine.
- Pregnant or breastfeeding.
- Subjects are not acceptable candidates if they received prior tumor infiltrating
lymphocytes (TIL) therapy (either in the setting of clinical trial or standard of
care if TIL therapy is FDA approved in the future), or an organ allograft.
- Has a known additional malignancy that is progressing or required active treatment
within the past 2 years. Note: participants with basal cell carcinoma of the skin,
squamous cell carcinoma of the skin, or carcinoma in situ (eg. Breast carcinoma,
cervical cancer in situ) that has undergone potentially curative therapy are not
excluded.
- Received a live or attenuated vaccine within 28 days prior to the beginning of the
lymphodepletion therapy.
Eligibility Criteria for Haploidentical Donors (For Arm 2 only)
- Donor must be at least 18 years of age.
- Donor must be willing, in general good health, and medically able to tolerate
leukapheresis required for harvesting the NK cells for this study.
- Donor must be negative for hepatitis, HTLV, and HIV on donor viral screen.
- Donor may not be pregnant and/or breastfeeding. Women of childbearing potential must
have a negative pregnancy test within 30 days prior to apheresis.
- Donor must be able to understand and willing to sign an IRB-approved written
informed consent document.
- Only haploidentical donors will be included.
- Donor must meet the requirements of institutional donor guidelines, including the
requirements of Foundation for the Accreditation of Hematopoietic Cell Therapy
(FACT) criteria.
Eligibility Criteria for Autologous Patients (For Arm 1 only)
- Patient must be willing and medically able to tolerate leukapheresis required for
harvesting the NK cells for this study.
- Patient must be negative for hepatitis, HTLV, and HIV on the viral screen.
- Patient may not be treated with any cytotoxic treatment within 2 weeks prior to
leukapheresis.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Washington University School of Medicine
Address:
City:
Saint Louis
Zip:
63110
Country:
United States
Status:
Recruiting
Contact:
Last name:
Alice Y Zhou, M.D., Ph.D.
Phone:
314-362-5677
Email:
alice.y.zhou@wustl.edu
Investigator:
Last name:
Alice Y Zhou, M.D., Ph.D.
Email:
Principal Investigator
Investigator:
Last name:
Todd A Fehniger, M.D., Ph.D.
Email:
Sub-Investigator
Investigator:
Last name:
Tanner M Johanns, M.D., Ph.D.
Email:
Sub-Investigator
Investigator:
Last name:
George Ansstas, M.D.
Email:
Sub-Investigator
Investigator:
Last name:
Charles Kaufman, M.D., Ph.D.
Email:
Sub-Investigator
Investigator:
Last name:
Ryan Fields, M.D.
Email:
Sub-Investigator
Investigator:
Last name:
Armin Ghobadi, M.D.
Email:
Sub-Investigator
Investigator:
Last name:
Amanda Cashen, M.D.
Email:
Sub-Investigator
Investigator:
Last name:
Feng Gao, M.D., Ph.D., MPH, MS
Email:
Sub-Investigator
Investigator:
Last name:
Jesse Keller, M.D.
Email:
Sub-Investigator
Start date:
November 6, 2024
Completion date:
November 30, 2030
Lead sponsor:
Agency:
Washington University School of Medicine
Agency class:
Other
Collaborator:
Agency:
Melanoma Research Alliance
Agency class:
Other
Collaborator:
Agency:
Rising Tide Foundation
Agency class:
Other
Source:
Washington University School of Medicine
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05629546
http://www.siteman.wustl.edu
