Trial Title:
A Phase Ib Study to Evaluate the Safety and Preliminary Efficacy of IL6-receptor Antibody Sarilumab in Combination With antiPD1 Antibody Cemiplimab for Patients With Non-small Cell Lung Cancer.
NCT ID:
NCT05704634
Condition:
Lung Cancer
Conditions: Official terms:
Lung Neoplasms
Cemiplimab
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Cemiplimab
Description:
Given by Injection under the skin every 2 weeks
Arm group label:
Cohort A : EGFR-mutant cohort
Arm group label:
Cohort B: LKB1-mutant cohort
Intervention type:
Drug
Intervention name:
Kevzara (Sarilumab)
Description:
Given by IV (vein) over about 30 minutes every 3 weeks.
Arm group label:
Cohort A : EGFR-mutant cohort
Arm group label:
Cohort B: LKB1-mutant cohort
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.
Criteria for eligibility:
Criteria:
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 exclusion criteria are
fulfilled:
1. Spinal cord compression or brain metastases unless asymptomatic or stable for at
least 2 weeks prior to start of study treatment.
2. Any unresolved toxicities from prior therapy greater than CTCAE grade 1 (with the
exception of alopecia grade 2) at the time of starting study treatment.
3. Any evidence of severe or uncontrolled systemic diseases. Screening for chronic
conditions is not required.
4. Woman of childbearing potential (WOCBP) not protected by highly-effective
contraceptive method(s) of birth control, and/or who are unwilling or unable to be
tested for pregnancy.
5. Pregnant or breastfeeding woman
6. Judgment by the investigator that the patient should not participate in the study if
the patient is unlikely to comply with study procedures, restrictions and
requirement.
7. Active or severe autoimmune disorders, including rheumatoid arthritis
8. Exclusion related to Tuberculosis (TB):
- Active TB or a history of incompletely treated TB regardless of screening
Quantiferon result
- Quantiferon positive patients (no active disease) are excluded from the study
unless the following conditions are met:
- Patients with a history of prior documented completed chemoprophylaxis for
latent tuberculosis infection (eg, acceptable treatments include 9 months of
isoniazid 300 mg oral daily or equivalent proven regimen per local guidelines)
or treatment of active tuberculosis infection (TBI) who has obtained
consultation with a specialist to rule out active TBI or the need to receive
further treatment.
- Patients with no prior history of chemoprophylaxis for latent TBI or treatment
for active TBI but have obtained consultation with a specialist to initiate an
appropriate regimen of chemoprophylaxis, based on local epidemiology and
applicable guidelines and have demonstrated compliance and tolerated treatment
for 1 month.
Consultations with and prior approval from IND sponsor are required in either of the
aforementioned scenarios.
- Clinically significant abnormality consistent with prior/active TB infection
based upon chest radiograph with at least posterior-anterior view (See Section
10.8.1). Additional lateral view is recommended but not required.
- Suspected extra-pulmonary TB infection regardless of screening Quantiferon
result.
- Patients at high risk of contracting TB, such as close contact with individuals
with active or latent TB.
- Patient who received Bacille Calmette Guerin -vaccination within 12 months
prior to screening.
9. Patients with a history of invasive opportunistic infections, including but not
limited to histoplasmosis, listeriosis, coccidioidomycosis, candidiasis,
pneumocystis jirovecii, aspergillosis despite resolution or John Cunningham virus
(progressive multifocal leukoencephalopathy).
10. Patients with fever (>38°C) associated with infection, or chronic, persistent, or
recurring infection(s) requiring active treatment with antibiotics, antivirals, or
antifungals within 4 weeks prior to the screening visit or other frequent recurrent
infections deemed unacceptable as per Investigator judgment.
11. Patients with uncontrolled diabetes mellitus, defined as glycosylated hemoglobin
(HbA1c) greater than 9% at the screening visit.
12. Patients with non-healed or healing skin ulcers.
13. Patients who received any live, attenuated vaccine within 3 months prior to the
baseline visit, such as varicella-zoster, oral polio or rubella vaccines.
14. Patients who are positive for hepatitis B surface antigen (HBsAg) or are positive
for total hepatitis B core antibody (HBcAb) with negative hepatitis B surface
antibody (HBsAb) or are positive for both HBcAb and HBsAb with presence of HBV DNA
at screening. E 25. Patients who are positive for hepatitis C antibody (HCV Ab).
15. Patients who are positive for human immunodeficiency virus (HIV) antibody test at
screening or who previously had a positive HIV antibody test, or who are suspected
to be positive for HIV.
16. Patients with a history of recurrent herpes zoster or active herpes zoster.
17. Patients with a history of prior articular or prosthetic joint infection.
18. Prior or current history of malignancy, including lymphoproliferative diseases,
other than adequately treated carcinoma in-situ of the cervix, non-metastatic
squamous cell or basal cell carcinoma of the skin, within 5 years prior to the
baseline visit.
19. Prior or current history of other significant concomitant illness(es) that,
according to Investigator's judgment, would adversely affect the patient's
participation in the study. These include, but are not limited to, cardiovascular
(including Stage III or IV cardiac failure according to the New York Heart
Association classification), renal, neurological (including demyelinating disease),
active infectious diseases, endocrinological, gastrointestinal, hepato-biliary,
metabolic, pulmonary, non-malignant lymphoproliferative disease or other lymphatic
disease(s).
20. Patients who have had surgery within 4 weeks prior to the screening visit or with
planned surgery during the course of the study.
21. Patients with a history of a systemic hypersensitivity reaction, other than
localized injection site reaction, to any biologic drug and known hypersensitivity
to any constituent of the sarilumab product.
22. Patients with a history of inflammatory bowel disease or severe diverticulitis or
previous gastrointestinal perforation.
23. Cognitively impaired adults.
24. Uncontrolled or significant heart disease, such as long QTc interval greater than
480ms on baseline EKG, NYHA III/IV heart failure or uncontrolled arrhythmia.
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:
Xiuning Le, MD,PHD
Phone:
713-792-6980
Email:
xle1@mdanderson.org
Investigator:
Last name:
Xiuning Le, MD,PHD
Email:
Principal Investigator
Start date:
August 18, 2023
Completion date:
January 1, 2028
Lead sponsor:
Agency:
M.D. Anderson Cancer Center
Agency class:
Other
Collaborator:
Agency:
Regeneron Pharmaceuticals
Agency class:
Industry
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/NCT05704634
http://www.mdanderson.org
