A clinical study evaluating efficacy and safety of inupadenant in combination with carboplatin and pemetrexed in adults with metastatic nonsquamous non-small cell lung cancer who have progressed on immunotherapy.
- Conditions
- onsquamous non-small cell lung cancerMedDRA version: 27.0Level: PTClassification code 10059515Term: Non-small cell lung cancer metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2021-005487-22-DE
- Lead Sponsor
- iTeos Belgium SA
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 192
1. Have signed an Institutional Review Board (IRB)/Independent Ethics
Committee (IEC) approved informed consent form prior to any studyspecific
evaluation.
2. Be =18 years of age at the time informed consent is signed.
3. Have histologically or cytologically confirmed diagnosis of metastatic
(Stage IV) or locally advanced, unresectable Stage III nonsquamous
NSCLC that has relapsed or progressed.
4. Have measurable disease as defined by RECIST v1.1 criteria based on
local assessment with at least 1 target lesion that has not been
previously irradiated.
5. PD-L1 expression status must be available prior to study entry. No
prespecified PD-L1 expression status is necessary for inclusion (or
enrollment).
6. Can provide a tumor sample from an existing biopsy taken within 4
years prior to entering the trial or have at least one lesion that is
accessible for a fresh biopsy where safe and feasible.
7. Have relapsed or progressed after prior anti PD-1/PD-L1 therapy as
follows:
- Have received only 1 anti-PD-1/PD-L1 agent in the metastatic setting,
without concomitant chemotherapy, and have radiographic progression
at least 12 weeks after the start of the anti-PD-1/PD-L1 therapy. One
cycle of chemotherapy while awaiting molecular testing results prior to
starting the anti-PD-1/PD-L1 agent is allowed. Immuno-oncology
(IO)/IO combination therapy (standard or investigational) is allowed.
OR
- Have received anti-PD-1/PD-L1 therapy concurrently with and/or
following chemoradiation in the Stage III unresectable setting and have
radiographic progression at least 6 months after the last dose of
chemotherapy and at least 12 weeks after the start of the anti-PD-1/PDL1
therapy. Immuno-oncology (IO)/IO combination therapy (standard
or investigational) is allowed.
Note: Prior re-treatment with the same anti-PD-1/PD-L1 agent as well
as prior SABR/SRS are allowed following progression on the anti-PD-
1/PD-L1 regimen.
8. Have adequate organ function confirmed by the following laboratory
values obtained within 14 days prior to treatment assignment:
Hematological:
- Absolute neutrophil count: =1,500 /mL
- Platelets: =100,000 /mL
- Hemoglobin: =9.5 g/dL or =5.9 mmol/L– 4 weeks without
transfusions
Renal:
- Estimated glomerular filtration rate (Modification of Diet in Renal
Disease method) (Levey, 1999) = 60mL/min
Hepatic
- Total bilirubin OR Direct bilirubin: Total bilirubin =1.5× institutional
upper limit of normal (ULN). For a participant with Gilbert's syndrome, total bilirubin =3.0 × institutional ULN is allowed if the increase is
predominantly unconjugated bilirubin.
- Alanine transaminase (ALT) and aspartate transaminase (AST): =3×
ULN; =5× ULN if liver metastases
Coagulation
- International Normalized Ratio (INR) : =1.5× ULN unless the
participant is receiving anticoagulant therapy.
9. Have an Eastern Cooperative Oncology Group (ECOG) performance
status of 0 or 1.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 48
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 144
1. Presence of symptomatic central nervous system (CNS) metastases or
leptomeningeal disease.
a. Participants with asymptomatic untreated CNS metastases are eligible
provided that immediate CNS-specific treatment is unlikely in the
Investigator's judgment.
b. Participants with previously treated CNS metastases are eligible
provided they are neurologically stable and, if receiving corticosteroids
for CNS metastases, are on a stable or decreasing corticosteroid dose for
at least 2 weeks prior to the start of study treatment.
c. In participants with known CNS metastases, baseline CNS imaging
must be obtained within 4 weeks prior to the start of study treatment.
2. Presence of active second malignancy, except for:
a. History of malignancy that has been successfully treated, with no
evidence of active cancer for 1 year prior to enrollment
b. Surgically cured and/or low risk tumors e.g., early stage cervical or
endometrial cancer, any cancer in situ, non-melanoma skin cancers.
3. Received systemic therapies for NSCLC, in the metastatic or Stage III
unresectable setting, other than 6 those described in inclusion criterion
7.
4. Have actionable mutation or genomic alteration in epidermal growth
factor receptor (EGFR), anaplastic lymphoma kinase (ALK), or ROS1.
Additionally, participants with known RET or NTRK rearrangement, BRAF
V600E mutation, HER2 mutation, or MET exon 14 skipping mutation are
excluded if targeted therapy is available as local standard of care (SOC).
5. Preexisting gastrointestinal disorders/conditions that would, in the
opinion of the Investigator, interfere with ingestion or absorption of
inupadenant.
6. History of or active (non-infectious) pneumonitis/ interstitial disease
or lung fibrosis. (Note: Stage III participants with pneumonitis Grade 1
from the prior chemoradiation therapy that did not worsen on PD-1/PDL1
therapy are allowed).
7. Have active or a history of autoimmune disease requiring systemic
treatment in the last 6 months (e.g., with disease modifying agents,
corticosteroids [>10mg daily prednisone equivalents], or
immunosuppressive drugs) or persistent immune-mediated toxicity
caused by checkpoint inhibitor therapy > Grade 1, with the exception of
residual endocrinopathy being adequately treated, vitiligo, Type 1
diabetes mellitus (T1DM), or psoriasis not requiring systemic therapy.
Replacement therapy (e.g., thyroxine, insulin, or corticosteroid replacement therapy for adrenal/pituitary insufficiency) is allowed.
8. Have known active or chronic hepatitis B or C infection unless treated
with antiviral therapy for at least 4 weeks with no detectable viral load
at the time of screening; known infection with human immunodeficiency
virus (HIV) unless receiving antiretroviral therapy with well-controlled
disease documented at the time of screening by a CD4+ T-cell count >
350 cell/µL, HIV ribonucleic acid (RNA) level of < 50 copies/mL or the
lower-limit of detection at least 12 weeks prior to screening, and a
stable treatment regimen for at least 4 weeks prior to enrollment that
has been limited to the use of abacavir, dolutegravir, emtricitabine,
lamivudine, raltegravir, rilpivirine, or tenofovir. Participants are not
required to be tested for the presence of such viruses prior to therapy on
this protocol in the absence of a history of such infection or unless
required by local health authorities.
9. History of life-threatening toxicity related to prior immune therapy or
any toxicity resulting in permanent disco
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method