Trial Title:
MOnaliZumab in Combination With durvAlumab (MEDI4736) Plus Platinum-based chemotheRapy for First-line Treatment of Extensive Stage Small Cell Lung Cancer
NCT ID:
NCT05903092
Condition:
Small Cell Lung Cancer
SCLC
Extensive Stage Small Cell Lung Cancer
Conditions: Official terms:
Lung Neoplasms
Small Cell Lung Carcinoma
Carboplatin
Etoposide
Durvalumab
Conditions: Keywords:
Small cell lung cancer
First-line therapy
Chemoimmunotherapy
Immunotherapy
Monalizumab
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:
Durvalumab
Description:
1500mg IV on Day 1 of every Cycle
Arm group label:
Durvalumab + Monalizumab + Chemotherapy
Other name:
Imfinzi
Intervention type:
Drug
Intervention name:
Monalizumab
Description:
1500mg IV on Day 1 of every Cycle
Arm group label:
Durvalumab + Monalizumab + Chemotherapy
Intervention type:
Drug
Intervention name:
Carboplatin or Cisplatin
Description:
On Day 1 of Cycles 1-4 by IV:
Carboplatin: AUC 5-6 OR Cisplatin: 75-80mg/m^2
Arm group label:
Durvalumab + Monalizumab + Chemotherapy
Intervention type:
Drug
Intervention name:
Etoposide
Description:
80-100mg/m^2 IV on Days 1-3 of Cycles 1-4
Arm group label:
Durvalumab + Monalizumab + Chemotherapy
Other name:
VP-16
Summary:
The study treatment will consist of a platinum drug (carboplatin or cisplatin per
investigator's choice) plus etoposide plus durvalumab plus monalizumab every 3 weeks for
4 cycles. After 4 cycles, subjects will continue maintenance treatment with durvalumab
plus monalizumab every 4 weeks until disease progression, unacceptable toxicity, decision
to stop study treatment, or withdrawal of consent. Patients who have received one prior
cycle of treatment before enrolling on the study will receive a total of 4 cycles with
monalizumab, durvalumab, and chemotherapy. There will be a safety lead-in phase,
including 6 to 12 patients, to confirm the safety of the proposed dose of monalizumab to
use in combination with chemotherapy and durvalumab.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
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. ECOG Performance Status of 0-2.
4. Histologically or cytologically confirmed diagnosis of small cell lung cancer:
- Extensive disease (American Joint Committee on Cancer Stage (8th edition) IV
SCLC [T any, N any, M1 a/b]), or
- T3-4 disease due to multiple lung nodules that are too extensive or have
tumor/nodal volume that is too large to be encompassed in a tolerable radiation
plan.
5. No prior systemic therapy for small-cell lung cancer, with the following exceptions:
--Up to one cycle of platinum doublet chemotherapy with or without durvalumab is
allowed up to 4 weeks prior to registration on this study. Patients with
irreversible toxicity not reasonably expected to be exacerbated by treatment with
durvalumab and monalizumab may be included only after consultation with the
sponsor-investigator. Patients should not have received trilaciclib.
6. Measurable disease according to RECIST v1.1
7. Subjects with treated brain metastasis and those with untreated asymptomatic brain
metastasis are eligible if they are clinically stable per investigator discretion
and not requiring systemic steroids for ≥ 7 days. Prophylactic cranial radiation
(PCI) is allowed per investigator's discretion.
8. Demonstrate adequate organ function. All screening labs to be obtained within 28
days prior to registration.
- Absolute Neutrophil Count (ANC) > 1500mm^3
- Hemoglobin ≥ 9 g/dL
- Platelet Count (PLT) ≥ 100,000 per mm3
- Calculated creatinine clearance ≥ 40 mL/min
- Bilirubin ≤ 1.5 × upper limit of normal (ULN); subjects with confirmed
Gilbert's syndrome (persistent or recurrent hyperbilirubinemia that is
predominantly unconjugated in the absence of hemolysis or hepatic pathology),
may be allowed with sponsor-investigator approval.
- Apsartate aminotransferase (AST) ≤ 2.5 x institutional upper limit of normal
unless liver metastases are present, in which case it must be ≤5x ULN
- Alanine aminotransferase (ALT) ≤ 2.5 x institutional upper limit of normal
unless liver metastases are present, in which case it must be ≤5x ULN
9. Females of childbearing potential must have a negative serum pregnancy test at
screening.
10. Females of childbearing potential and male subjects must be willing to abstain from
heterosexual intercourse or to use an effective method(s) of contraception.
11. Life expectancy of ≥ 12 weeks.
12. Patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral
load must be undetectable on suppressive therapy, if indicated. Patients with a
history of hepatitis C virus (HCV) infection must have been treated and cured. For
patients with HCV infection who are currently on treatment, the HCV viral load must
be undetectable through PCR to be eligible for this trial. Testing is not required
for screening unless mandated by local authorities. Local guidelines for testing
should be followed.
Exclusion Criteria:
1. Body weight ≤ 40 kg.
2. Receipt of radiotherapy to the chest within 6 months prior to initiating systemic
therapy or planned consolidation chest radiation therapy. NOTE: Radiation therapy
outside of the chest for palliative care (e.g., bone metastasis) is allowed but must
be completed before the first dose of the study medication.
3. Active infection requiring intravenous antibiotic therapy.
4. Known allergy or hypersensitivity to any of the study drugs or any of the study drug
excipients.
5. Major surgical procedure (as defined by the investigator) within 28 days prior to
the first dose of study treatment. NOTE: Local surgery of isolated lesions for
palliative intent is acceptable.
6. History of active primary immunodeficiency.
7. Known to have tested positive for human immunodeficiency virus (HIV) (positive HIV
1/2 antibodies) or active tuberculosis infection (clinical evaluation that may
include clinical history, physical examination and radiographic findings, or
tuberculosis testing in line with local practice).
8. Presence of neurologic paraneoplastic syndrome.
9. Active or prior documented autoimmune or inflammatory disorders (including
inflammatory bowel disease [e.g., ulcerative colitis or Crohn's disease], systemic
lupus erythematosus, sarcoidosis, Wegener syndrome [granulomatosis with
polyangiitis], rheumatoid arthritis, hypophysitis, uveitis, etc). The following are
exceptions to this criterion:
- Patients with vitiligo or alopecia
- Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on
hormone replacement
- Any chronic skin condition that does not require systemic therapy
- Patients without active disease in the last 2 years may be included but only
after consultation with the study physician
- Patients with celiac disease controlled by diet alone
10. Current or prior use of immunosuppressive medication within 7 days before the first
dose of monalizumab and 'on-study' durvalumab. The following are exceptions to this
criterion:
- Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra
articular injection)
- Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of
prednisone or its equivalent
- Steroids as premedication for hypersensitivity reactions (e.g., CT scan
premedication), and for prevention of chemotherapy induced nausea/vomiting per
institutional standards.
11. Receipt of live attenuated vaccine within 30 days prior to the first dose of study
treatment. NOTE: Subjects, if enrolled, should not receive live vaccine whilst
receiving study treatment and up to 30 days after the last dose of study treatment.
12. Uncontrolled intercurrent illness, including but not limited to, ongoing or active
infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable
angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic
gastrointestinal conditions associated with diarrhea, or psychiatric illness/social
situations that would limit compliance with study requirement, substantially
increase risk of incurring AEs or compromise the ability of the patient to give
written informed consent.
13. Patients who have received prior one dose of durvalumab along with chemotherapy:
- Must not have experienced a toxicity that led to permanent discontinuation of
prior immunotherapy.
- Must not have experienced a ≥Grade 3 immune related AE or an immune related
neurologic or ocular AE of any grade while receiving prior immunotherapy. NOTE:
Patients with endocrine AE of ≤ Grade 2 are permitted to enroll if they are
stably maintained on appropriate replacement therapy and are asymptomatic.
- Must not have required the use of additional immunosuppression other than
corticosteroids for the management of an AE and not currently require
maintenance doses of > 10 mg prednisone or equivalent per day.
14. Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while
the mother is being treated on study).
15. Patients with a prior or concurrent malignancy whose natural history or treatment
has the potential to interfere with the safety or efficacy assessment of the
investigational regimen, per investigator discretion.
16. History of leptomeningeal carcinomatosis.
17. History of allogeneic organ transplantation.
18. Treatment with any investigational drug within 28 days prior to registration or
concurrent enrolment in another clinical study, unless observational in nature.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Indiana University Melvin and Bren Simon Comprehensive Cancer Center
Address:
City:
Indianapolis
Zip:
46202
Country:
United States
Status:
Recruiting
Contact:
Last name:
Margaret Uhrich, RN
Email:
muhrich@iu.edu
Investigator:
Last name:
Misty Shields, MD, PhD
Email:
Principal Investigator
Facility:
Name:
University of Iowa Hospitals and Clinics
Address:
City:
Iowa City
Zip:
52242
Country:
United States
Status:
Recruiting
Contact:
Last name:
David Akinbo
Email:
david-akinbo@uiowa.edu
Investigator:
Last name:
Muhammad Furqan, MD
Email:
Principal Investigator
Facility:
Name:
Karmanos Cancer Center (Wayne State University)
Address:
City:
Detroit
Zip:
48201
Country:
United States
Status:
Recruiting
Contact:
Last name:
Hirva Mamdani, MD
Phone:
313-576-8711
Email:
mamdanih@karmanos.org
Investigator:
Last name:
Hirva Mamdani, MD
Email:
Principal Investigator
Facility:
Name:
University of Virginia Health System
Address:
City:
Charlottesville
Zip:
22908
Country:
United States
Status:
Recruiting
Contact:
Last name:
Lacey Garrett
Email:
lb5tu@uvahealth.org
Investigator:
Last name:
Ryan Gentzler, MD
Email:
Principal Investigator
Start date:
September 26, 2023
Completion date:
January 3, 2027
Lead sponsor:
Agency:
Hirva Mamdani
Agency class:
Other
Collaborator:
Agency:
AstraZeneca
Agency class:
Industry
Collaborator:
Agency:
Barbara Ann Karmanos Cancer Institute
Agency class:
Other
Source:
Hoosier Cancer Research Network
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05903092
