Study of Inupadenant (EOS100850) With Chemotherapy as Second Line Treatment for Nonsquamous Non-small Cell Lung Cancer

iTeos Therapeutics

Status and phase: Enrolling; Phase 2

Conditions: Metastatic NSCLC - Non-Small Cell Lung Cancer; Locally Advanced NSCLC - Non-Small Cell Lung Cancer

Treatments: Drug: Pemetrexed; Drug: inupadenant; Drug: Placebo; Drug: Carboplatin

Study type: Interventional

Funder types: Industry

Identifiers

NCT05403385

A2A-005

Details and patient eligibility

About

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.

Full 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.

Enrollment: 186 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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186 participants in 3 patient groups, including a placebo group

Part 1, open label

Experimental group

Description:

Inupadenant will be given at one or more dose levels to determine the recommended Phase 2 dose (RP2D).

Treatment:

Drug: Carboplatin

Drug: inupadenant

Drug: Pemetrexed

Part 2, active treatment

Experimental group

Description:

Treatment with inupadenant combined with carboplatin and pemetrexed

Treatment:

Drug: Carboplatin

Drug: inupadenant

Drug: Pemetrexed

Part 2, placebo

Placebo Comparator group

Description:

Treatment with matched placebo combined with carboplatin and pemetrexed

Treatment:

Drug: Carboplatin

Drug: Placebo

Drug: Pemetrexed