Trial Title:
Phase II Study of Nivolumab in Combination With Relatlimab in Patients With Active Melanoma Brain Metastases
NCT ID:
NCT05704647
Condition:
Melanoma (Skin)
Conditions: Official terms:
Melanoma
Brain Neoplasms
Nivolumab
Relatlimab
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
BMS-986213 (Relatlimab-Nivolumab FDC)
Description:
Given by IV (vein)
Arm group label:
Relatlimab+Nivolumab
Other name:
Relatlimab
Other name:
BMS-986016
Intervention type:
Drug
Intervention name:
Nivolumab
Description:
Given by IV (vein)
Arm group label:
Relatlimab+Nivolumab
Intervention type:
Drug
Intervention name:
Relatlimab
Description:
Given by IV (vein)
Arm group label:
Relatlimab+Nivolumab
Summary:
To learn if giving nivolumab in combination with relatlimab can help to control melanoma
that has spread to the brain (melanoma with brain metastases). The safety and side
effects of the study drug combination will also be studied.
Detailed description:
Primary Objectives:
• To assess the intracranial objective response rate (iORR), defined as intracranial CR +
PR per modified RECIST 1.1 criteria, of nivolumab + relatlimab (nivo+rela) in subjects
with MBM and treatment naïve to anti-PD-1 agents in the metastatic setting.
Secondary Objectives:
- To determine the safety of the combination of nivo+rela
- To assess the clinical benefit rate (CBR), defined as CR + PR + SD >6 months, of the
combination
- To determine overall response rates (intracranial + extracranial), DoR, PFS, and
using a modified version of iRANO and compared to modified RECIST v1.1 and Response
Assessment in Neuro-oncology - Brain Metastases (RANO-BM) for patients treated with
nivo+rela
- To determine the 1-year intracranial progression-free survival rate for the
combination of nivo+rela
- To determine overall survival
- Advanced MRI imaging to assess for edema, tumor response, and predictors of response
and radiation necrosis
- To evaluate the brain-specific safety and tolerability of the combination regimen in
subjects with or without SRT received prior to study entry, or on study
- To evaluate changes in neurocognitive function and health-related quality of life
- To assess available tumor tissue - intracranial and/or extra cranial - in specimens
obtained at baseline (archival and/or fresh tissue), on treatment, and at time of
progression
- To assess immune cell subsets by flow cytometry, TCR NGS for diversity and
clonality, cytokine expression, cfDNA from peripheral blood.
Exploratory Endpoints:
- Radiotherapy-assisted PFS defined as time from study treatment initiation to the
first occurrence of disease progression or death from any cause, whichever occurs
first, as determined by the investigator according to RECIST v1.1 modified by
excluding ≤ 5 lesions that can be treated by SRT from the sum of largest diameters
from baseline onwards.
- To explore the association between baseline and on-treatment gut microbiome features
with response and toxicity
- To understand the association between habitual diet and gut microbiome features in
this study population.
- To explore predictors of biological response through the change in metabolic
parameters
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Age ≥ 18 years old.
2. Life Expectancy > 12 weeks.
3. Subjects must have signed and dated an IRB/IEC approved written informed consent
form in accordance with regulatory and institutional guidelines. This must be
obtained before the performance of any protocol related procedures that are not part
of normal subject care.
• Subjects must be willing and able to comply with scheduled visits, treatment
schedule, laboratory testing, and other requirements of the study.
4. Histologically confirmed malignant melanoma with measurable metastases in the brain
(≥ 0.5 cm).
5. At least one measurable intracranial target lesion, which previously was not treated
with local therapy (no prior SRS to this lesion).
• Largest diameter of ≥ 0.5cm, but ≤ 3cm as determined by contrast-enhanced MRI.
6. Representative formalin-fixed paraffin-embedded (FFPE) tumor specimens in paraffin
blocks (blocks are preferred) OR at least 4 unstained slides, with an associated
pathology report, for testing of tumor PD-L1 expression:
- Tumor tissue should be of good quality based on total and viable tumor content.
- Patients who do not have tissue specimens may undergo a biopsy during the
screening period. Acceptable samples include core-needle biopsies for deep
tumor tissue or excisional, incisional, punch, or forceps biopsies for
cutaneous, subcutaneous, or mucosal lesions. Fine Needle Aspirations (FNA) will
not be considered acceptable for tissue procurement.
- Tumor tissue from bone metastases is not evaluable for PD-L1 expression and is
therefore not acceptable.
- However, if repeat biopsy is not feasible, and no archival tissue available
patient still may be enrolled.
7. Prior SRT and prior excision of up to 5 MBM is permitted if there has been complete
recovery, with no neurologic sequelae, and measurable non irradiated lesions remain.
8. Growth or change in a lesion previously irradiated will not be considered
measurable. Regrowth in cavity of previously excised lesion will not be considered
measurable.
• Any prior SRT to brain lesions or prior excision must have occurred ≥ 1 weeks
before the start of dosing for this study.
9. Radiation to NON-CNS lesions. Prior radiation to NON-CNS is allowed and does not
require a washout period for treatment initiation.
10. Subjects must be free of neurologic signs and symptoms related to metastatic brain
lesions and must not have required or received systemic corticosteroid therapy in
the 5 days prior to beginning protocol therapy.
11. ECOG performance status ≤1.
12. Adequate organ function as described below.
13. Women of child-bearing potential (WOCBP) must not be breastfeeding and must have a
negative pregnancy test within 3 days prior to initiation of dosing. She must agree
to use an acceptable method of birth control from the time of the negative pregnancy
test, through the duration of treatment with the study combination plus 5 half lives
of study treatment for a total of 5 months post -treatment completion. WOCBP must
agree to adhere to the contraceptive guidance in Appendix 5. NOTE: A female
participant is eligible to participate if she is not a woman of childbearing
potential as defined Appendix 4.
14. All associated toxicity from previous or concurrent cancer therapy must be resolved
(to ≤ grade 1 or baseline) prior to study treatment administration. This excludes
non-serious toxicities. However, stable endocrinopathies requiring replacement
therapy will be allowed.
15. Steroids for physiological replacement are allowed.
Exclusion Criteria:
1. History of known leptomeningeal involvement (lumbar puncture not required).
2. Previous stereotactic or highly conformal radiotherapy within 1 weeks before the
start of dosing for this study. NOTE: The stereotactic radiotherapy field must not
have included the brain index lesion(s).
3. Subjects previously treated with SRT > 5 lesions in the brain. Prior whole brain
radiation is not allowed.
4. Brain lesion size > 3 cm.
5. Prior checkpoint inhibitor therapy in the metastatic setting
• Patients who received ipilimumab and/or anti-PD1 as adjuvant or neoadjuvant
therapy must have a 6-month washout before receiving any dosing on this study.
6. Subjects with an active, known or suspected autoimmune disease. Subjects with type I
diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders
(such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or
conditions not expected to recur in the absence of an external trigger are permitted
to enroll.
7. Subjects with major medical, neurologic or psychiatric condition who are judged as
unable to fully comply with study therapy or assessments should not be enrolled.
8. Subject has a history of a second malignancy, unless potentially curative treatment
has been completed with no evidence of malignancy for 2 years. Note: The time
requirement does not apply to participants who underwent successful treatment of
superficial bladder cancer, in situ cervical cancer, or other in-situ cancers.
Subjects with a completely treated prior malignancy and no evidence of disease for ≥
2 years are eligible.
a. Skin Cancer Exclusion: Please note that basal cell carcinoma and squamous cell
carcinoma is exempt from needing resection prior to treatment. (Resection can be
completed after the start of treatment).
9. Has a known history of or is positive for hepatitis B (hepatitis B surface antigen
[HBsAg] reactive) or hepatitis C (hepatitis C virus [HCV] RNA [qualitative] is
detected).
a. NOTE: Without known history, testing needs to be performed to determine
eligibility. Hepatitis C antibody (Ab) testing is allowed for screening purposes in
countries where HCV RNA is not part of standard of care.
10. Has a known history of human immunodeficiency virus (HIV) infection. No HIV testing
is required unless mandated by local health authority.
11. The use of corticosteroids is not allowed for 10 days prior to initiation of therapy
(based upon 5 times the expected half-life of dexamethasone) except patients who are
taking steroids for physiological replacement. If alternative corticosteroid therapy
has been used, consultation with the PI is required to determine the washout period
prior to initiating study treatment.
12. Subjects with a condition requiring systemic treatment with either corticosteroids
(≤ 10 mg daily prednisone equivalent) or other immunosuppressive medications within
14 days of study initiation. Inhaled or topical steroids, and adrenal replacement
steroid doses > 10 mg daily prednisone equivalent, are permitted in the absence of
active autoimmune disease.
13. Major surgical procedure, open biopsy (excluding skin cancer resection), or
significant traumatic injury within 14 days of initiating study drug (unless the
wound has healed) or anticipation of the need for major surgery during the study.
14. Non-healing wound, ulcer, or bone fracture.
15. Women who are breast-feeding or pregnant.
16. Uncontrolled intercurrent illness (i.e., active infection ≥ grade 2) or concurrent
condition that, in the opinion of the Investigator, would interfere with the study
endpoints or the subject's ability to participate.
17. History of clinically significant cardiac disease or congestive heart failure > New
York Heart Association (NYHA) class 2. Subjects must not have unstable angina
(anginal symptoms at rest) or new-onset angina within the last 3 months or
myocardial infarction within the past 6 months or a history of myocarditis.
18. Troponin T (TnT) or I (TnI) > 2 × institutional ULN. Participants with TnT or TnI
levels between > 1 to 2 × ULN will be permitted if repeat levels within 24 hours are
≤ 1 ULN. If TnT or TnI levels are between >1 to 2 × ULN within 24 hours, the
participant may undergo a cardiac consultation and be considered for treatment,
following cardiologist recommendation. When repeat levels within 24 hours are not
available, a repeat test should be conducted as soon as possible. If TnT or TnI
repeat levels beyond 24 hours are < 2 × ULN, the participant may undergo a cardiac
consultation and be considered for treatment, following cardiologist recommendation.
Notification of the decision to enroll the participant following cardiologist
recommendation has to be made to the principal investigator.
19. Investigational drug use within 14 days (or 5 half-lives, whichever is longer) of
the first dose of nivolumab and relatlimab.
20. With a history of non-infectious pneumonitis that required steroids or current
pneumonitis.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
M D Anderson Cancer Center
Address:
City:
Houston
Zip:
77030
Country:
United States
Status:
Recruiting
Contact:
Last name:
Hussein Tawbi, MD,PHD
Phone:
713-792-4185
Email:
htawbi@mdanderson.org
Investigator:
Last name:
Hussein Tawbi, MD,PHD
Email:
Principal Investigator
Start date:
February 23, 2023
Completion date:
December 31, 2026
Lead sponsor:
Agency:
M.D. Anderson Cancer Center
Agency class:
Other
Source:
M.D. Anderson Cancer Center
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05704647
http://www.mdanderson.org
