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

Metastatic NSCLC Clinical Trial

Official title:

A Randomized, Double-blind, Placebo-controlled, Phase 2 Study Evaluating Efficacy and Safety of Inupadenant in Combination With Carboplatin and Pemetrexed in Adults With Nonsquamous Non-small Cell Lung Cancer Who Have Progressed on Immunotherapy

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05403385
• Other study ID #: A2A-005
• Status: Recruiting
• Phase: Phase 2
• Start date: August 26, 2022
• Est. completion date: May 2025

Study information

• Verified date: September 2023
• Source: iTeos Therapeutics
• Contact: Medical Monitor
• Phone: +32 71 91 99 33
• Email: clinical_info[@]iteostherapeutics.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Part 1 of the study determines the optimal dose of inupadenant to be given in combination with carboplatin and pemetrexed to patients that progressed after receiving specific first line treatments for Stage 3 or metastatic non-small cell lung cancer. Part 2 compares the efficacy of inupadenant to placebo when both are combined with carboplatin and pemetrexed for patients that progressed after receiving the same first line treatments for Stage 3 or metastatic non-small cell lung cancer.

Description:

In both Part 1 and Part 2, there are two nonsquamous NSCLC patient populations eligible for the study treatment: 1)patients with Stage III, non-resectable cancer that have received chemoradiotherapy, followed by durvalumab, and then have progressed; 2)patients who have received only first-line immunotherapy with anti-PD-L1 therapy, but no chemotherapy, in the metastatic setting, then progressed. In Part 1, all participants receive open-label inupadenant with standard of care doses of carboplatin and pemetrexed. Carboplatin is given at q3week intervals for no more than 4 cycles; pemetrexed continues at q3week as prescribed by the Investigator. Inupadenant is given orally BID. Dose-limiting toxicities are monitored during the first 21 days of treatment and a modified 3+3 escalation method is utilized to determine the recommended phase 2 dose (RP2D). Imaging and safety and PRO assessments are performed during the treatment and follow-up phase. Treatment continues until progression, withdrawal of consent, start of new anti-cancer treatment, end of study, or death. Part 2 is double-blinded, with subjects randomized 1:1 to receive the RP2D of inupadenant or matched placebo. All subjects receive the carboplatin and pemetrexed per standard of care. Imaging, safety and PRO assessments are performed during the treatment and follow-up phase. Treatment continues until progression, withdrawal of consent, start of new anti-cancer treatment, end of study, or death. In both Parts 1 and 2, blood samples are drawn to further define the pharmacokinetic profile of inupadenant and biosamples are collected for additional exploratory analyses.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 192
• Est. completion date: May 2025
• Est. primary completion date: April 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Confirmed diagnosis of metastatic (Stage IV) or locally advanced, unresectable (Stage III) NSCLC of nonsquamous pathology that has relapsed or progressed

2. Measurable disease as defined by RECIST v1.1 criteria

3. PD-L1 expression status available at or after the time of diagnosis of advanced or metastatic NSCLC disease

4. Can provide existing biopsy taken within 2 years prior to entering trial or provide fresh biopsy

5. Have relapsed or progressed after prior anti- PD-(L)1 therapy as follows:

1. At least 12 weeks of treatment with only 1 line of anti-PD-(L)1 therapy (mono or combo) in the metastatic setting, without concomitant chemotherapy OR

2. At least 12 weeks of single-agent durvalumab

6. Adequate organ function

7. ECOG performance status of 0 to 1.

Exclusion Criteria:

1. Symptomatic and/or untreated central nervous system (CNS) metastases or leptomeningeal disease.

2. Presence of active second malignancy

3. EGFR or ALK mutation. Participants with presence of other driver mutations are allowed if targeted therapy is not available as per local standard of care.

4. Preexisting gastrointestinal disorders/conditions that may interfere with ingestion or absorption of oral medications.

5. History of or active (non-infectious) pneumonitis/ interstitial disease or lung fibrosis, except for Grade 1 pneumonitis from prior chemoradiation therapy (Stage III patients).

6. History of or active autoimmune disease requiring systemic treatment in the last 6 months or persistent immune-mediated toxicity caused by checkpoint inhibitor therapy > Grade 2

7. Known active or chronic hepatitis B or C infection unless adequately treated for at least 4 weeks with no detectable viral load; known infection with human immunodeficiency virus (HIV) unless receiving antiretroviral therapy with well-controlled disease.

8. History of life-threatening toxicity related to prior immune therapy or any toxicity resulting in permanent discontinuation from prior therapy.

9. Diagnosis of immunodeficiency or any condition requiring concurrent use of systemic immunosuppressants or corticosteroids.

10. Active infection requiring systemic therapy = 7 days prior to first dose of study treatment.

11. Any other oncologic treatments administered =14 days (<28 days in case of checkpoint inhibitor therapy) prior to first dose of study treatment. Also, ongoing adverse effects from such treatment > Grade 1 with the exception for alopecia and Grade 2 peripheral neuropathy.

12. Non-study related minor surgical procedure =7 days, or major surgical procedure of = 5 weeks prior to first dose of study treatment.

13. Uncontrolled or significant cardiovascular disease

14. History of allergy or hypersensitivity to any of the study treatments.

15. Treatment with a live or live attenuated vaccine.

16. Treatment with moderate or strong inducers or inhibitor of CYP 3A4, inhibitors of P-glycoprotein, or substrates of breast cancer resistance protein

17. Pregnant or breast-feeding

18. Male and Female participants: Lack of agreement to use highly effective method of contraception during treatment and for 6 months after the last administration of chemotherapy

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Metastatic NSCLC
• Stage III NSCLC

Intervention

Drug:
• inupadenant
Adenosine 2a receptor antagonist
• Placebo
matched placebo capsule to inupadenant
• Carboplatin
standard of care chemotherapeutic, alkylating agent
• Pemetrexed
standard of care chemotherapeutic, anti-metabolite

Locations

Country	Name	City	State
Belgium	Algemeen Ziekenhuis Sint-Lucas	Gent
Belgium	Jessa Ziekenhuis	Hasselt
Belgium	Algemeen Ziekenhuis Sint-Maarten	Mechelen
Belgium	C.H.U. Ambroise Pare	Mons
Belgium	CHU UCL Namur	Namur
Belgium	AZ Delta	Roeselare
Canada	William Osler Health System	Brampton	Ontario
Czechia	Fakultni nemocnice Olomouc	Olomouc
Czechia	Vseobecna Fakultni Nemocnice	Praha
Czechia	Vseobecna Fakultni Nemocnice	Praha
France	Hopital Saint Andre - CHU de Bordeaux	Bordeaux
France	Institut Bergonie - Centre Regional de Lutte Contre Le Cancer de Bordeaux et Sud Ouest	Bordeaux
France	CHU de Caen	Caen
France	Centre Georges Francois Leclerc	Dijon
France	Hopital Nord de Marseille	Marseille
France	HIA Begin	Saint-Mandé
Italy	Azienda Ospedaliera Spedali Civili di Brescia	Brescia
Italy	Ospedale San Luca	Lucca
Italy	Fondazione Irccs Ca Granda Ospedale Maggiore Policlinico	Milan
Italy	Istituto Nazionale dei Tumori	Milano
Italy	Oncologia Casa Di Cura Polispecialistica Dott Pederzoli	Peschiera del Garda
Italy	Gruppo Humanitas - Istituto Clinico Humanitas	Rozzano
Poland	Szpital Specjalistyczny im. Ludwika Rydygiera w Krakowie Sp. z o.o	Krakow
Poland	Uniwersytet Medyczny w Lodzi Klinika Pulmonologii Ogolnej i Onkologicznej	Lódz
Poland	Warminsko Mazurskie Centrum Chorob Pluc w Olsztynie	Olsztyn	Warminsko-Mazurskie
Poland	Nzoz Formed 2	Oswiecim
Poland	NZOZ Ars Medical Sp. z o.o.	Pila
Poland	NZOZ Medpolonia Sp. Z o.o.	Poznan
Poland	Centrum Onkologii-Instytut im. Marii Sklodowskiej-Curie	Warszawa	Mazowieckie
Spain	Centro Oncologico de Galicia	A Coruña
Spain	Hospital General Universitario de Alicante	Alicante
Spain	Hospital Infanta Cristina	Badajoz
Spain	Hospital Quiron Barcelona - Instituto Oncologico Baselga	Barcelona
Spain	Consorcio Hospitalario Provincial de Castellon	Castellón De La Plana
Spain	Hospital Universitario Lucus Augusti	Lugo
Spain	Hospital Universitario Fundacion Jimenez Diaz	Madrid
Spain	Althaia Hospital	Manresa
Spain	Complejo Hospitalario Universitario de Ourense	Ourense
Spain	Hospital Universitario Son Espases	Palma De Mallorca	Illes Balears
Spain	Complejo Hospitalario de Navarra (CHN)	Pamplona
Spain	Hospital Universitari i Politecnic La Fe de Valencia	Valencia
Switzerland	Centre Hospitalier Universitaire Vaudois	Lausanne
Switzerland	HFR Fribourg	Villars-sur-Glâne
Switzerland	Stadt Zuerich Stadtspital Triemli	Zürich
United States	Gabrail Cancer & Research Center	Canton	Ohio
United States	Carolina Institute for Clinical Research	Fayetteville	North Carolina
United States	Highlands Oncology Group	Fayetteville	Arkansas
United States	Summit Medical Group PA	Florham Park	New Jersey
United States	Gettysburg Cancer Center	Gettysburg	Pennsylvania
United States	Nebraska Cancer Specialists	Omaha	Nebraska
United States	Mid-Florida Hematology & Oncology Centers, PA	Orange City	Florida
United States	Moffitt Cancer Center	Tampa	Florida
United States	UT Health East Texas HOPE Cancer Center	Tyler	Texas
United States	Innovative Clinical Research Institute (ICRI)	Whittier	California

Sponsors (1)

Lead Sponsor	Collaborator
iTeos Belgium SA

Countries where clinical trial is conducted

United States,  Belgium,  Canada,  Czechia,  France,  Italy,  Poland,  Spain,  Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dose-finding to determine recommended Phase 2 dose	Incidence of dose-limiting toxicities	At the end of Cycle 1 (each cycle is 21 days)
Primary	Incidence of treatment-emergent adverse events [Safety and Tolerability]	Incidence of adverse events (AEs), serious adverse events, AEs leading to discontinuation, deaths, and clinically significant laboratory abnormalities.	Duration of intervention (up to 24 months) plus 30 days follow-up
Primary	Progression-free survival [Efficacy]	Time from first dose to the date of first documented radiologic progression per RECIST v1.1 or time of death, which ever comes first	From randomization to first-documented radiological progression or date of death from any cause, whichever comes first, assessed up to 24 months.
Secondary	Overall Response Rate [Efficacy]	Proportion of participants with a best overall response of complete (CR) or partial (PR) response as assessed by RECIST v1.1	From randomization to first-documented radiological improvement, if applicable, assessed up to 24 months.
Secondary	Duration of Response [Efficacy]	Time from first CR or PR to first documented progression or death from any cause, per RECIST v1.1	From first-documented CR or PR to first radiological progression or date of death, whichever comes first, assessed up to 24 months.
Secondary	Percent Change in Tumor Size [Efficacy]	Change in sum of size of target tumors from baseline, per RECIST v1.1	From randomization to the documented radiological assessment with the smallest tumor size sum, assessed up to 24 months.
Secondary	Disease Control Rate [Efficacy]	Proportion of participants with CR, PR, or stable disease (SD) sustained over at least 2 consecutive tumor assessments, per RECIST v1.1	From randomization to second-documented radiological CR, PR or SD, if applicable, assessed up to 24 months.
Secondary	Overall Survival [Efficacy]	Time from randomization to date of death due to any cause.	From randomization to death due to any cause, assessed up to 24 months.
Secondary	Efficacy (Patient Reported Outcomes)	Time to definitive deterioration in global health status/quality of life	Duration of intervention (up to 24 months) plus 30 days follow-up
Secondary	Peak plasma concentration (Cmax)	Cmax for inupadenant and its primary metabolite as observed by assessment of concentration-time profile	From first dose of inupadenant through 24 hours
Secondary	Time to peak plasma concentration (Tmax)	Tmax for inupadenant and its primary metabolite as observed by assessment of concentration-time profile	From first dose of inupadenant through 24 hours
Secondary	Plasma half-life (T-1/2)	T-1/2 for inupadenant and its primary metabolite	At the end of Cycle 12 (each cycle is 3 weeks)
Secondary	Area under the concentration-time curve (AUCinf)	AUC from Time 0 extrapolated to infinity for inupadenant and its primary metabolite	At the end of Cycle 12 (each cycle is 3 weeks)