Locally Advanced NSCLC - Non-Small Cell Lung Cancer, Metastatic NSCLC - Non-Small Cell Lung Cancer
Conditions
Keywords
non-squamous NSCLC, second line, 2L, adenosine, immunotherapy
Brief summary
The study will first determine the optimal dose of inupadenant to be given in combination with carboplatin and pemetrexed to patients that progressed after receiving first line anti-PD(L)1 treatment for locally advanced or metastatic non-small cell lung cancer. The efficacy and safety of the combination is then compared to standard of care carboplatin and pemetrexed in the same populations.
Detailed description
The study is composed of two parts. Part 1 follows an open-label, dose-finding design where individual cohorts are treated with various dose levels of inupadenant combined with standard of care dosing of carboplatin and pemetrexed. The recommended phase 2 dose is determined prior to initiation of Part 2 which then compares inupadenant to placebo with both arms treated in combination with standard of care carboplatin and pemetrexed. Participants in both parts are enrolled from two populations of patients with nonsquamous NSCLC that have progressed after first line treatment as follows: non-resectable patients treated with chemoradiotherapy followed by anti-PD-(L)1 or metastatic patients treated with anti-PD-(L)1 therapy without chemotherapy. Imaging, safety and PRO assessments are performed during the treatment and follow-up phase as well as pharmacokinetic and other exploratory analyses.
Interventions
DRUGinupadenant
Adenosine 2a receptor antagonist
DRUGPlacebo
matched placebo capsule to inupadenant
DRUGCarboplatin
standard of care chemotherapeutic, alkylating agent
DRUGPemetrexed
standard of care chemotherapeutic, anti-metabolite
Sponsors
iTeos Belgium SA
iTeos Therapeutics
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Quadruple masking : The dose-finding part (Part 1) of this study is open-label whereas the randomized part (Part 2) is double-blinded. Therefore, for Part 2, the subject, the Investigator and Sponsor personnel or delegate(s) who are involved in the treatment administration or clinical evaluation of the subjects will be unaware of the group assignments. The chemotherapy agents administered during Part 2 will be open label.
Intervention model description
Single Group Assignment Part 1 sequential dose escalation. Part 2 randomized double-blind.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Confirmed diagnosis of metastatic (Stage IV) or locally advanced, unresectable (Stage III) NSCLC of nonsquamous pathology * Measurable disease as defined by RECIST v1.1 * PD-L1 expression status available at or after the time of diagnosis. All levels of expression are eligible. * Existing biopsy taken within 4 years prior to entering trial or provide fresh biopsy where safe and feasible * At least 12 weeks of treatment with only 1 anti-PD-(L)1 agent (mono or with IO combo) in the metastatic setting, OR at least 12 weeks of anti-PD-(L)1 agent (mono or with IO combo) following CRT in the unresectable, Stage III setting * ECOG performance status of 0 to 1.
Exclusion criteria
* Symptomatic central nervous system (CNS) metastases or leptomeningeal disease. * EGFR, ALK, or ROS1 mutation. * Autoimmune disease requiring systemic treatment or immunodeficiency requiring concurrent use of systemic immunosuppressants or corticosteroids * Hepatitis B or C infection unless adequately treated with no detectable viral load; Human immunodeficiency virus (HIV) unless well-controlled disease on therapy. * History of life-threatening toxicity related to prior immune therapy * Uncontrolled or significant cardiovascular disease * Pregnant or breast-feeding * Lack of agreement to use highly effective method of contraception during treatment and for 6 months after the last administration of chemotherapy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose-finding to determine recommended Phase 2 dose | At the end of Cycle 1 (each cycle is 21 days) | Incidence of dose-limiting toxicities |
| Incidence of treatment-emergent adverse events [Safety and Tolerability] | Duration of intervention (up to 24 months) plus 30 days follow-up or up to database lock | Incidence of adverse events (AEs), serious adverse events, AEs leading to discontinuation, deaths, and clinically significant laboratory abnormalities. |
| Progression-free survival [Efficacy] | From randomization to first-documented radiological progression or date of death from any cause, whichever comes first, assessed up to 24 months. | Time from first dose to the date of first documented radiologic progression per RECIST v1.1 or time of death, whichever comes first |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Disease Control Rate [Efficacy] | From randomization to second-documented radiological CR, PR or SD, if applicable, assessed up to 24 months or up to database lock. | Proportion of participants with CR, PR, or stable disease (SD) sustained over at least 2 consecutive tumor assessments, per RECIST v1.1 |
| Overall Response Rate [Efficacy] | From randomization to first-documented radiological improvement, if applicable, assessed up to 24 months or up to database lock. | Proportion of participants with a best overall response of complete (CR) or partial (PR) response as assessed by RECIST v1.1 |
| Overall Survival [Efficacy] | From randomization to death due to any cause, assessed up to 24 months or up to database lock. | Time from randomization to date of death due to any cause. |
| Duration of Response [Efficacy] | From first-documented CR or PR to first radiological progression or date of death, whichever comes first, assessed up to 24 months or up to database lock. | Time from first CR or PR to first documented progression or death from any cause, per RECIST v1.1 |
| Percent Change in Tumor Size [Efficacy] | From randomization to the documented radiological assessment with the smallest tumor size sum, assessed up to 24 months or up to database lock. | Change in sum of size of target tumors from baseline, per RECIST v1.1 |
Countries
Belgium, Canada, Czechia, France, Italy, Spain, Switzerland, United States
Outcome results
None listed