Lung Cancer
Conditions
Brief summary
To learn if the combination of sarilumab (also called Kevzara) and cemiplimab can help to control EGFR- or LKB1/STK11-mutant NSCLC.
Detailed description
Primary Objective: * To evaluate the safety of sarilumab cemiplimab combination in metastatic lung cancer patients. * The primary endpoint is DLT for safety Run-In cohort. * To preliminarily assess efficacy of sarilumab cemiplimab combination in patients with EGFR- or LKB1/STK11-mutant NSCLC respectively. * The primary efficacy endpoint is objective response rate (ORR) in cohort A and cohort B, evaluated separately. Secondary Objectives: --To evaluate the progression-free survival (PFS), disease control rate (DOR), duration of response (DoR), overall survival (OS), and safety and tolerability of this combination in patients with EGFR- or LKB1-mutant NSCLC respectively. Correlative/Exploratory Objectives: * Explore the association of baseline genomic profiles (from tumor, germline DNA, and ctDNA) with clinical benefit in patients treated with sarilumab and cemiplimab combination * Explore the association of immune profiles (tumor immune microenvironment features) with clinical benefit in patients treated with sarilumab and cemiplimab combination * Explore resistance mechanisms to sarilumab and cemiplimab combination. * Determine the impact of sarilumab on immunotherapy-related side effects from cemiplimab.
Interventions
DRUGCemiplimab
Given by Injection under the skin every 2 weeks
DRUGKevzara (Sarilumab)
Given by IV (vein) over about 30 minutes every 3 weeks.
Sponsors
M.D. Anderson Cancer Center
Regeneron Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Subject must meet all of the following applicable inclusion criteria to participate in this study: 1. Written informed consent and HIPAA authorization for release of personal health information prior to registration. NOTE: HIPAA authorization may be included in the informed consent or obtained separately. 2. Age ≥ 18 years at the time of consent. 3. Histologically or cytologically confirmed non-squamous, non-small cell lung cancer 4. Locally advanced or metastatic disease. 5. Patients must have one of the following: Cohort A: * NSCLC which harbours EGFR Exon 19 deletion. * NSCLC which harbours EGFR L858R mutation. * NSCLC with activating EGFR exon20 insertion or exon 18/21 atypical mutations EGFR deletion/mutation must be documented by a Clinical Laboratory Improvement Amendments (CLIA) certified test (either from tissue or ctDNA from blood is allowed) The documentation of EGFR mutation status can be obtained any time since the initial diagnosis of non-small cell lung cancer. For cohort A, the patient must have received an EGFR TKI treatment, if approval targeted therapy exists. For patients whose tumor harboring EGFR Exon19 deletion or L858R mutation, prior osimertinib treatment is required, unless contraindicated for medical reasons. Cohort B: • NSCLC which harbours LKB1 mutation. LKB1 mutation must be documented by a Clinical Laboratory Improvement Amendments (CLIA) certified test (either from tissue or ctDNA from blood is allowed) The documentation of LKB1 mutation status can be obtained any time since the initial diagnosis of non-small cell lung cancer. 6. Eastern Cooperative Oncology Group (ECOG) performance status 0-1 (Appendix A) 7. At least one lesion, not previously irradiated and not chosen for biopsy during the study screening period, that can be accurately measured at baseline at equal or greater than 10mm in the longest dimension by RECIST 1.1. 8. Prior treatment with cytotoxic chemotherapy or immunotherapy is allowed for both cohorts. Up to 3 lines of prior therapy is allowed. 9. Patients must have adequate hematologic, coagulation, hepatic, and renal function. All laboratory tests must be obtained less than 4 weeks from study entry. This includes: * ANC \>/= 2,000/mm3 and white blood cells \>/= 3,000/mm3 * platelet count \>/=150,000/mm3 * HgB ≥ 8.5 g/dL * Creatinine ≤ 30 mL/minute (using Cockroft-Gault formula). * Total Serum Bilirubin ≤ ULN (unless with documented Gilbert Syndrome diagnosed by genetic testing) * SGOT, SGPT ≤ 1.5 X ULN * Cholestrol ≤ 350 mg/dL, 9.1 mmol/L, and triglyceride ≤ 500 mg/dL, 5.6 mmol/. 10. Females of childbearing potential must not be breast feeding and must have a negative serum or urine pregnancy test within 7 days of starting of treatment. The patient must agree to use adequate contraception for a minimum of two weeks prior to receiving study medication until 3 months after discontinuation of the study medication. Acceptable methods of contraception include total and true sexual abstinence, hormonal contraceptives that are not prone to drug-drug interactions (IUS Levonorgestrel Intra Uterine System (Mirena), Medroxyprogesterone injections (Depo-Provera)), copper-banded intra-uterine devices, and vasectomized partner. All hormonal methods of contraception should be used in combination with the use of a condom by their sexual male partner. Females of childbearing potential are defined as those who are not surgically sterile (i.e., bilateral tubal ligation, bilateral oophorectomy, or complete hysterectomy) or postmenopausal (defined as 12 months with no menses without an alternative medical cause). Women will be considered post-menopausal if they have been amenorrheic for the past 12 months without an alternative medical cause. The following age-specific requirements must also apply: Women \< 50 years old: they would be considered post-menopausal if they have been amenorrheic for the past 12 months or more following cessation of exogenous hormonal treatments. The levels of Luteinizing Hormone (LH) and Follicle-Stimulating Hormone (FSH) must also be in the post-menopausal range (as per the institution). Women ≥ 50 years old: they would be considered post-menopausal if they have been amenorrheic for the past 12 months or more following cessation of all exogenous hormonal treatments, or have had radiation-induced oophorectomy with the last menses \> 1 year ago, or have had chemotherapy-induced menopause with \>1 year interval since last menses, or have had surgical sterilization by either bilateral oophorectomy or hysterectomy. 11. Non-sterilized males who are sexually active with a female partner of childbearing potential must use adequate contraception for the duration of the study and 3 months after the last dose of study medication. Adequate contraception methods include: birth control pills (e.g. combined oral contraceptive pill), barrier protection (e.g. condom plus spermicide, cervical/vault cap or intrauterine device), and abstinence. Patients should not father a child for 6 months after completion of the study medication. Patients should refrain from donating sperm from the start of dosing until 6 months after discontinuing the study medication. If male patients wish to father children they should be advised to arrange for freezing of sperm samples prior to the start of the study medication. 12. Patients who meet eligibility criteria to either Cohort A or B will be allowed to enroll to the run-in cohort.
Exclusion criteria
Subjects should not enter the study if any of the following
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0 | through study completion; an average of 2 years |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORXiuning Le, MD,PHD
M.D. Anderson Cancer Center
Outcome results
None listed