Trial Title:
Immune Profile Selection By Fraction of ctDNA in Patients With Advanced NSCLC Treated With Immunotherapy
NCT ID:
NCT05715229
Condition:
Carcinoma, Non-Small-Cell Lung
Conditions: Official terms:
Carcinoma, Non-Small-Cell Lung
Paclitaxel
Carboplatin
Nivolumab
Pemetrexed
Ipilimumab
Conditions: Keywords:
Advanced Non Small Cell Lung Cancer (NSCLC)
Metastatic NSCLC
circulating tumor DNA (ctDNA)
G360
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Intervention model description:
Subjects will be randomized 2:1 and patients in both arms will begin treatment with
nivolumab 360 mg intravenously every 3 weeks and ipilimumab 1 mg/kg intravenously every 6
weeks. At five weeks of treatment, subjects will have ctDNA response evaluation with
Guardant360 Response assay. At the next cycle of treatment (+/- 2 days), patients in the
arm A will receive treatment based on the Guardant360 Response assay results, as
described below. Arm B will continue the immunotherapy only.
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Nivolumab
Description:
Immunotherapy
Arm group label:
Arm A
Arm group label:
Arm B
Other name:
Opdivo
Intervention type:
Drug
Intervention name:
Ipilimumab
Description:
Immunotherapy
Arm group label:
Arm A
Arm group label:
Arm B
Other name:
Yervoy
Intervention type:
Drug
Intervention name:
Carboplatin
Description:
Chemotherapy
Arm group label:
Arm A
Other name:
Paraplatin
Intervention type:
Drug
Intervention name:
Paclitaxel
Description:
Chemotherapy
Arm group label:
Arm A
Other name:
Taxol
Other name:
Paxel
Intervention type:
Drug
Intervention name:
Pemetrexed
Description:
Chemotherapy
Arm group label:
Arm A
Other name:
Alimta
Other name:
Pemfexy
Summary:
This clinical trial plans to assess to what extent the on-treatment circulating tumor DNA
(ctDNA) can predict the subset of patients with NSCLC who will respond to immunotherapy
treatment only and which patients will need both immunotherapy and chemotherapy
modalities for their treatment regimen.
Detailed description:
Subjects will be randomized 2:1 and patients in both arms will begin treatment with
nivolumab 360 mg intravenously every 3 weeks and ipilimumab 1 mg/kg intravenously every 6
weeks. At five weeks of treatment, subjects will have ctDNA response evaluation with
Guardant360 Response assay. At the next cycle of treatment (+/- 2 days), patients in the
larger arm will receive treatment based on the Guardant360 Response assay results, as
described below. Subjects will undergo ctDNA evaluation with Guardant360 Response assay
6- week post-randomization and at the time of progression. Response to therapy will be
assessed by interval imaging with CT scan of the chest/abdomen/pelvis (and MRI brain if
applicable) with response evaluated by irRECIST criteria every 12 weeks until disease
progression.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Eligible patients will have newly diagnosed, previously untreated histologically
documented Stage IV NSCLC
2. Eligible patients will be required to have positive PD-L1 expression ≥1% by IHC
using Dako 22C3 assay.
3. Patients will require a baseline Guardant360 CDx test prior to enrollment
4. Patients willing to undergo serial ctDNA testing as required by protocol
5. Patients will be over the age of 18
6. Life expectancy ≥12 weeks
7. Measurable (RECIST 1.1) indicator lesion not previously irradiated, with measurable
disease determined per the treating investigator.
8. Prior palliative radiotherapy to non-CNS lesions must have been completed at least 2
weeks prior to randomization
9. ECOG Performance Score ≤2
10. Adequate organ function
11. Hemoglobin > 9 g/dL
12. Platelets > 100,000mm3 or 100 x 109/L
13. AST, ALT < 2.5 x ULN with no liver metastases or < 5x ULN with the presence of liver
metastases
14. Total bilirubin < 1.5 x ULN if no liver metastases or < 3 x ULN in the presence of
documented Gilbert's Syndrome (unconjugated hyperbilirubinemia) or liver metastases
15. Absolute neutrophil count (ANC) > 1500 cells/mm3
16. Creatinine ≤ 1.5 x ULN OR calculated creatinine clearance ≥ 60ml/min calculated by
Cockcroft and Gault's equation
17. Willing to use highly effective contraceptive measures if child-bearing potential or
if the patient's sexual partner is a woman of childbearing potential: a. Female
subjects should be using a highly effective contraceptive measures, and must have a
negative pregnancy test and not be breast-feeding prior to starting of dosing if of
child-bearing potential or must have evidence of non-child-bearing potential by
fulfilling one of the following criteria at screening: i. Post-menopausal is defined
as aged more than 50 years and amenorrheic for at least 12 months following
cessation of all exogenous hormonal treatments ii. Women under 50 years old would be
considered postmenopausal if they have been amenorrheic for 12 months or more
following cessation of exogenous hormonal treatments and with LH and FSH levels in
the the post-menopausal range for the institution iii. Documentation of irreversible
surgical sterilization by hysterectomy, bilateral oophorectomy, or bilateral
salpingectomy but not a tubal ligation b. Male subjects should be willing to use
barrier contraception
Exclusion Criteria:
1. Patients under the age of 18
2. Inability to provide informed consent by either the patient or the authorized
representative
3. Patients with known EGFR, ALK, ROS1, MET, and RET oncogenic driver alterations that
have approved first-line targeted therapies are excluded from the study (All
patients must have a tissue or blood-based testing to identify these driver
alterations)
4. Patients with no detectable ctDNA or ctDNA VAF ≤ 0.3% on Guardant360 CDx at baseline
5. Subjects with untreated CNS metastases are excluded.
6. Subjects are eligible if CNS metastases are adequately treated and subjects are
neurologically returned to baseline (except for residual signs or symptoms related
to the CNS treatment) for at least 2 weeks prior to randomization. In addition,
subjects must be either off corticosteroids, or on a stable or decreasing dose of 10
mg daily prednisone (or equivalent) for at least 2 weeks prior to randomization.
7. Subjects with carcinomatous meningitis
8. Subjects must have recovered from the effects of major surgery or significant
traumatic injury at least 14 days before randomization
9. Subjects with previous malignancies (except non-melanoma skin cancers, and in situ
cancers such as the following: bladder, gastric, colon, cervical/dysplasia,
melanoma, or breast) are excluded unless a complete remission was achieved at least
2 years prior to randomization and no additional therapy is required or anticipated
to be needed during the study period.
10. Other active malignancy requiring concurrent intervention.
11. Subjects with an active, known, or suspected autoimmune disease. Subjects with type
I diabetes mellitus, and hypothyroidism only require 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.
12. Subjects with a condition requiring systemic treatment with either corticosteroids
(> 10 mg daily prednisone equivalent) or other immunosuppressive medications within
14 days of randomization. Inhaled or topical steroids, and adrenal replacement
steroids > 10 mg daily prednisone equivalent, are permitted in the absence of active
autoimmune disease.
13. Subjects with interstitial lung disease that is symptomatic or may interfere with
the detection or management of suspected drug-related pulmonary toxicity.
14. Significant uncontrolled cardiovascular disease, including but not limited to, any
of the following:
1. Uncontrolled hypertension, which is defined as systolic blood pressure > 160 mm
Hg or diastolic blood pressure > 100 mm Hg despite optimal medical management.
2. Active coronary artery disease, including unstable all newly diagnosed angina
within 3 months of study enrollment.
3. Myocardial infarction in the past 6 months.
4. History of congenital long QT syndrome.
5. History of clinically significant arrhythmias, such as ventricular tachycardia,
ventricular fibrillation, or torsade de pointes.
6. Uncontrolled heart failure, defined as class III of 4 by the New York Heart
Association functional classification.
7. History of a current diagnosis of myocarditis.
15. the Known medical condition that, in the investigator's opinion, would increase the
risk associated with study participation or study drug administration or interfere
with the interpretation of safety results.
16. Any positive test for hepatitis B virus or hepatitis C virus indicating acute or
chronic infection
17. Subjects with Grade 2 peripheral neuropathy
18. Life expectancy <12 weeks
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Lombardi Comprehensive Cancer Center, Georgetown University
Address:
City:
Washington
Zip:
20007
Country:
United States
Status:
Not yet recruiting
Facility:
Name:
John Theurer Cancer Center, Hackensack Meridian Health
Address:
City:
Hackensack
Zip:
07410
Country:
United States
Status:
Recruiting
Contact:
Phone:
551-996-2000
Facility:
Name:
Jersey Shore University Medical Center
Address:
City:
Neptune
Zip:
07753
Country:
United States
Status:
Not yet recruiting
Contact:
Last name:
Walter Elliot
Email:
Walter.Elliott@hmhn.org
Contact backup:
Last name:
Suzanne Kosky
Phone:
551-996-3986
Email:
Suzanne.Kosky@hmhn.org
Start date:
September 29, 2023
Completion date:
April 28, 2026
Lead sponsor:
Agency:
Hackensack Meridian Health
Agency class:
Other
Collaborator:
Agency:
MedSIR
Agency class:
Other
Source:
Hackensack Meridian Health
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05715229
https://clinicaltrials.gov/ct2/show/NCT00527735?term=00527735&draw=2&rank=1
https://www.opdivo.com/about-opdivo/how-the-combination-works-combinationtherapy
