Nonsquamous non-small cell lung cancer MedDRA version: 21.1 Level: PT Classification code 10059515 Term: Non-small cell lung cancer metastatic System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: Inupadenant 20 mg
Product Code: EOS100850
Pharmaceutical Form: Capsule
INN or Proposed INN: Inupadenant
CAS Number: 2411004-22-1
Current Sponsor code: EOS100850
Concentration unit: mg mi
Sponsors
iTeos Belgium SA
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Have signed an Institutional Review Board (IRB)/Independent Ethics Committee (IEC) approved informed consent form prior to any study-specific 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 the 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 2 years prior to entering 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 anty-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 unrespectable setting and have radiographic progression at least 6 months after the last doe of chemotherapy and at least 12 weeks after the start of the ant-PD-1/PD-L1 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) = 60 mL/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 =3.0x 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) or Prothrombin Time (PTT): =1.5× ULN unless the subject 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
Exclusion criteria
Exclusion criteria: 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 the 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 participations 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 systematic therapies for NSCLC, in the metastatic or Stage III unrespectable setting, other than 6 those described in inclusion criterion 7. 4. Have actionable mutation or genomic alteration in epidermal growth factor receptor (EGFR) or 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/PD-L1 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 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 disc
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Part 1 (Dose-Finding): • To evaluate safety and tolerability of inupadenant in combination with carboplatin and pemetrexed • To identify the inupadenant recommended Phase 2 dose (RP2D) to be used in combination with carboplatin and pemetrexed in Part 2 of the study Part 2 (Randomized): • To evaluate efficacy of inupadenant in combination with carboplatin and pemetrexed compared to the efficacy of the placebo in combination with carboplatin and pemetrexed ;Secondary Objective: Part 1 Only: • To evaluate efficacy of inupadenant in combination with carboplatin and pemetrexed Part 2 Only: • To evaluate safety and tolerability of inupadenant in combination with carboplatin and pemetrexed vs. placebo in combination with both drugs • To evaluate additional measures of efficacy of inupadenant in combination with carboplatin and pemetrexed vs. placebo in combination with both drugs • To assess the effect of inupadenant in combination with carboplatin and pemetrexed vs. placebo in combination with both drugs on time to onset and/or deterioration of lung cancer specific symptoms Part 1 and Part 2: • To evaluate pharmacokinetics of inupadenant and active metabolite EOS100612 in combination with carboplatin and pemetrexed Please refer to Protocol Section 2 for other secondary objectives.;Primary end point(s): Part 1 (Dose-Finding): • Incidence of adverse events (AEs), serious adverse events (SAEs), dose-limiting toxicities (DLTs), AEs leading to dose-modifications or discontinuation, deaths, and clinically significant laboratory abnormalities. Part 2 (Randomized): • Progression-free survival (PFS), defined as time from randomization to the date of first documented radiological progression using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria or death due to any cause. ;Timepoint(s) of evaluation of this end point: AEs/SAEs/DLTs: Continuously from first intake of study drug up to 30 day follow-up visit or start of a new therapy, whi | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Part 1 (Dose-Finding) Only: •Overall response rate (ORR); duration of response; percent change in tumor size (CTS) from baseline; disease control rate (DCR), PFS, overall survival (OS). Part 2 (Randomized) Only: • Incidence and frequency of AEs, SAEs, and AEs leading to dose modifications or discontinuation, deaths, and clinically significant laboratory abnormalities. • ORR; duration of response; percent CTS from baseline; DCR; disease control rate; OS. • Time to definitive deterioration in global health status/quality of life (QoL), shortness of breath and pain per European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life of Cancer Patients (QLQ-C30) questionnaire. • Time to definitive 10-point deterioration symptom scores of pain, cough, and dyspnea per EORTC Lung (QLQ-LC13) questionnaire. Part 1 and Part 2: • Summary measures of pharmacokinetic (PK) parameters of inupadenant and active metabolite EOS100612 on Day1 and at steady state. Please refer to Protocol Section 2 for other secondary endpoints.;Timepoint(s) of evaluation of this end point: AEs/SAEs and tumour assessment: as above. Survival status: every 12 weeks until death, withdrawal of consent, lost to follow-up, or end of study. QoL questionnaire: Days 1 of all Cycles; EoT; Day 30 after last dose. PK: Days 1 and 8 of Cycles 1 and 2; Day 1 of cycles 3 and 4 and once anytime between cycle 5 and cycle 12; EoT. Unscheduled PK sample should be collected at the onset of the first Grade =3 AE(s) that is at least possibly related to the study drug. | — |
Countries
Belgium, Canada, Czechia, France, Germany, Italy, Poland, Spain, Switzerland, United Kingdom, United States
Contacts
Public ContactSally Ross
iTeos Belgium SA
Outcome results
None listed