Efficacy and Safety Evaluation of Inupadenant Hydrochloride with Carboplatin and Pemetrexed in Metastatic Nonsquamous Non-Small Cell Lung Cancer Post-Immunotherapy

Trial ID: 2024-515393-27-00
Protocol: A2A-005
Sponsor: iTeos Belgium

Trial statistics

science

test molecules

location_city

research sites

public

countries

medical_information

disease

person_search

investigators

handshake

vendors

Diseases & Conditions

Non-small cell lung cancer metastatic

Objectives

The primary objective of this study is to evaluate the **safety** and tolerability of inupadenant in combination with carboplatin and pemetrexed in adults with nonsquamous non-small cell lung cancer who have progressed on immunotherapy. Additionally, the study aims to identify the recommended Phase 2 dose (RP2D) of inupadenant for use in combination with these chemotherapeutic agents. This is clinically relevant as it seeks to establish a safe and effective dosing regimen for inupadenant, potentially offering a new therapeutic option for patients with this type of lung cancer.

Secondary objectives include: - Part 1: Evaluating the efficacy of inupadenant in combination with carboplatin and pemetrexed. - Part 2: Assessing the safety and tolerability of inupadenant versus placebo, evaluating additional efficacy measures, and determining the effect on the time to onset and/or deterioration of lung-cancer-specific symptoms. - Both Parts: Evaluating the pharmacokinetics of inupadenant and its active metabolite EOS100612 in combination with carboplatin and pemetrexed.

Participants

The clinical trial involves a total of **55 participants** diagnosed with **nonsquamous non-small cell lung cancer**. The study population includes both male and female subjects, aged 18 years and older, who have a confirmed diagnosis of metastatic or locally advanced, unresectable Stage III nonsquamous NSCLC that has relapsed or progressed. Participants were selected based on their ability to provide informed consent and meet specific health criteria, including adequate organ function and an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. The trial does not specify any particular lifestyle considerations such as diet or physical activity. The inclusion of a vulnerable population is noted, although specific details are not provided. Key criteria for participation include having measurable disease as defined by RECIST v1.1 criteria and having relapsed or progressed after prior anti PD-1/PD-L1 therapy. The trial aims to evaluate the safety, tolerability, and efficacy of inupadenant in combination with carboplatin and pemetrexed.

Plans and Procedures

The clinical trial is a **randomized, double-blind, placebo-controlled** Phase 2 study designed to evaluate the efficacy and safety of **inupadenant hydrochloride** in combination with carboplatin and pemetrexed in adults with metastatic nonsquamous non-small cell lung cancer who have progressed on immunotherapy. The trial is structured in two parts: Part 1 focuses on dose-finding to assess the safety and tolerability of inupadenant in combination with carboplatin and pemetrexed, and to identify the recommended Phase 2 dose. Part 2 is randomized to evaluate the efficacy of the inupadenant combination compared to a placebo combination. The trial is expected to conclude by April 2027, with recruitment having started in June 2022.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, diagnosis, and organ function. Following successful screening, participants will be enrolled and randomized to receive either the inupadenant combination or placebo. Study visits will include regular follow-up assessments to monitor safety, efficacy, and any adverse events. The end-of-study visit will occur after the completion of the treatment period or upon early termination. The expected length of participant involvement is up to 21 days for the treatment period, with additional time for follow-up assessments.

Participants may be withdrawn from the study early due to reasons such as significant adverse events, disease progression, or withdrawal of consent. The primary endpoints include the incidence of adverse events and progression-free survival, while secondary endpoints encompass overall response rate, duration of response, and quality of life assessments. The trial aims to provide valuable insights into the potential benefits of inupadenant in this patient population, contributing to the development of new therapeutic strategies for nonsquamous non-small cell lung cancer.

Treatment

The clinical trial involves the administration of **Inupadenant HCl**, an experimental medication, in the form of a **capsule**. The active substance, **inupadenant hydrochloride**, is a chemical entity developed by ITEOS THERAPEUTICS SA. The medication is administered orally. The trial aims to determine the recommended Phase 2 dose (RP2D) of inupadenant when used in combination with carboplatin and pemetrexed. The maximum treatment period for inupadenant is 21 days. The dosing schedule and specific dosage amounts are not explicitly detailed in the provided data.

A **placebo** is also utilized in this study as a comparator treatment. The placebo is designed to match the inupadenant capsule in appearance but does not contain the active substance. The placebo is used to evaluate the efficacy of inupadenant in combination with carboplatin and pemetrexed by providing a control group for comparison. The administration route and form of the placebo are not specified in the data.

In addition to the experimental treatments, the study involves the use of standard-of-care therapies, **carboplatin** and **pemetrexed**, which are commonly used in the treatment of nonsquamous non-small cell lung cancer. These medications are administered according to standard dosing regimens, which are not detailed in the provided data. Participant compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the treatment protocol.

Efficacy

The efficacy of the investigational product, **Inupadenant HCl**, in combination with carboplatin and pemetrexed, will be assessed in a randomized, double-blind, placebo-controlled Phase 2 clinical trial involving adults with nonsquamous non-small cell lung cancer who have progressed on immunotherapy. The primary efficacy endpoint for Part 2 of the study is progression-free survival (PFS), defined as the time from randomization to the date of first documented radiological progression using the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria or death due to any cause. Secondary efficacy endpoints include overall response rate (ORR), duration of response (DoR), disease control rate (DCR), overall survival (OS), and time to definitive deterioration in global health status/quality of life (QoL), shortness of breath, and pain as measured by the EORTC QLQ-C30 questionnaire.

Data collection for these endpoints will be conducted at specified intervals throughout the trial, with radiological assessments performed according to RECIST v1.1 criteria. The analysis of efficacy data will involve comparing the outcomes of the treatment group receiving Inupadenant HCl with those of the placebo group, both in combination with carboplatin and pemetrexed. The trial is designed to provide robust data on the efficacy of Inupadenant HCl in this patient population, with the aim of determining its potential benefit in improving clinical outcomes for individuals with advanced nonsquamous non-small cell lung cancer.

Inclusion and Exclusion Criteria

check_circle

Inclusion Criteria

Have signed an Institutional Review Board (IRB)/Independent Ethics Committee (IEC) approved informed consent form prior to any study specific evaluation.
Be ≥18 years of age at the time informed consent is signed
Have histologically or cytologically confirmed diagnosis of metastatic (Stage IV) or locally advanced, unresectable Stage III nonsquamous NSCLC that has relapsed or progressed
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
PD-L1 expression status must be available prior to study entry. No prespecified PD-L1 expression status is necessary for inclusion (or enrollment)
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
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-PD1/PD-L1 regimen.
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.
Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

cancel

Exclusion Criteria

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.
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.
Received systemic therapies for NSCLC, in the metastatic or Stage III unresectable setting, other than 6 those described in inclusion criterion 7.
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).
Preexisting gastrointestinal disorders/conditions that would, in the opinion of the Investigator, interfere with ingestion or absorption of inupadenant.
History of or active (non-infectious) pneumonitis/ interstitial disease or lung fibrosis.
Have active or a history of autoimmune disease requiring systemic treatment in the last 6 months 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 is allowed.
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. 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.
History of life-threatening toxicity related to prior immune therapy or any toxicity resulting in permanent discontinuation from prior immune therapy.
Diagnosis of immunodeficiency or any condition requiring concurrent use of systemic immunosuppressants or corticosteroids (>10mg daily prednisone equivalents).
Active infection requiring systemic antibacterial, antifungal, or antiviral therapy ≤ 7 days prior to first dose of study treatment.
Oncologic treatment including radiation, antibody therapy or other immunotherapy, gene therapy, vaccine therapy, targeted therapy, and/or experimental drugs administered ≤14 days (<28 days in case of checkpoint inhibitor therapy) prior to first dose of study treatment and/or ongoing adverse effects from such treatment > Grade 1.
Major surgical procedure ≤4 weeks prior to first dose of study treatment; participants with major surgical procedure >4 weeks prior to first dose of study treatment must be sufficiently recovered and stable before treatment administration. Please refer to Protocol Section 3.5.2 for other exclusion criteria

Trial Status by Country

Country	Status	Start of Recruitment	Planned Patients
Belgium	Not Recruiting	30 Jun 2022	16
Czechia	Not Recruiting	30 Jun 2022	10
France	Not Recruiting	30 Jun 2022	23
Germany	Not Recruiting	30 Jun 2022	23
Italy	Not Recruiting	30 Jun 2022	26
Spain	Not Recruiting	30 Jun 2022	33