Part 1A will evaluate the safety as well as to determine the maximum tolerated dose (MTD) and the recommended phase 2 dose (RP2D) of inupadenant in participants with advanced solid tumors.

The effect of food on the exposure to inupadenant will be investigated.

Inupadenant

Medical Director, MD

Tom Van der Mooter, MD PhD

Laurence Buisseret, MD, PhD

Jean-Pierre Machiels, MD, PhD

Sylvie Rottey, MD, PhD

Johan DeBono, MD, PhD

A Multicenter, Open-Label, Phase I Clinical Study to assess the Safety, Tolerability, Pharmacokinetics and Food-Effect of Inupadenant New Formulation in Participants with Advanced Solid Tumors

Arm A sequential dose escalation Arm B randomized crossover

New Formulation Study of Inupadenant (EOS100850) in Patients With Cancer

A Multicenter, Open-Label, Phase I Clinical Study to Assess the Safety, Tolerability, Pharmacokinetics and Food-Effect of Inupadenant New Formulation in Participants With Advanced Solid Tumors

Incidence of adverse events (AEs), serious adverse events (SAEs), DLTs, AEs leading to discontinuation, deaths, electrocardiogram (ECG) abnormalities, and clinically significant laboratory abnormalities

To assess safety and tolerability as measured by incidence and severity of AEs

Determined by inspection of the concentration-time profile

Assessment of preliminary efficacy of inupadenant

iTeos Therapeutics

Antineoplastic Agents

All Drugs and Chemicals

Pembrolizumab

Paclitaxel

Albumin-Bound Paclitaxel

Carboplatin

Tubulin Modulators

Antimitotic Agents

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Dose Escalation- EOS100850 Monotherapy: to confirm RP2D

EOS100850 and Pembrolizumab Combination Therapy: to confirm RP2D as combination

Dose Expansion- Monotherapy: to explore safety, PK, PD, and antitumor activity of inupadenant as monotherapy

Dose Expansion - EOS100850 and Pembrolizumab Combination Therapy: to explore safety, PK, PD, and antitumor activity of inupadenant in combination with pembrolizumab in melanoma and CRPC patients

Dose expansion - EOS100850 and Chemotherapy: to explore safety, PK, PD, and antitumor activity of inupadenant in combination with chemotherapy SOC carboplatin and paclitaxel in patients with TNBC

Dose expansion - EOS100850 Monotherapy : to evaluate the safety, PD, and antitumor activity of inupadenant as monotherapy at the mono-RP2D in BMK-H participants in 4 disease-specific cohorts: NSCLC; HNSCC; EC; and other forms of cancer

EOS100850

Chemotherapy

Multicenter, open-label, dose-escalation Phase I/Ib clinical study to evaluate the safety and tolerability, the MTD/RP2D, pharmacokinetics (PK), pharmacodynamics (PD), and antitumor activity of EOS100850 as a Single Agent and in Combination with Pembrolizumab and/or Chemotherapy in Participants with Advanced Cancers.

First-in-Human Study of EOS100850 in Patients With Cancer

Phase I/Ib First-in-Human Study of EOS100850 as a Single Agent and in Combination With Pembrolizumab and/or Chemotherapy in Participants With Advanced Cancers

To define the maximum tolerated dose (MTD) or the recommended Phase 2 dose (RP2D) of EOS100850 in patients receiving EOS100850

Assessment of preliminary efficacy of EOS100850

Merck Sharp & Dohme LLC

Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Carcinoma

Carcinoma, Bronchogenic

Bronchial Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Anti-Arrhythmia Agents

Vasodilator Agents

Analgesics

Micronutrients

Hematinics

Vitamins

Pemetrexed

Immunomodulating Agents

Antimetabolites

Adenosine

Alkylating Agents

Enzyme Inhibitors

Folic Acid

Vitamin B Complex

Folic Acid Antagonists

Folinic Acid

Folate

Vitamin B9

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

Treatment with inupadenant combined with carboplatin and pemetrexed

Treatment with matched placebo combined with carboplatin and pemetrexed

inupadenant

Placebo

standard of care chemotherapeutic, alkylating agent

standard of care chemotherapeutic, anti-metabolite

Medical Monitor

Eric Schaefer, MD

Sami Ali

Santosh Nair, MD

Clinical Trial Navigator

Albert Chiappori, MD

Ralph Hauke, MD

Michelle Mackenzie, RN

William DeRosa, MD

Kenneth Manning, MD

Carrie Smith, RN

Nashat Gabrail, MD

Satish Shah, MD

Arielle S Lee, MD

Elke Govaerts

Kristof Cuppens, MD MSc

Marc Lambrechts

Stephane Hobrechts

Jean-Charles Goeminne, MD

Ingel Demedts, MD, PhD

Kristin Perdrizet, MD

Bohuslav Melichar, MD

Milada Zemanova, MD

Milada Zemanova

Charlotte Domblides, MD

Sophie Cousin, MD

Simon DeShayes

Laure Favier, MD

AdmTrials-MultiOnco@ap-hm.fr

Laurent Greillier, MD, PhD

Carole Helissey-Danis, MD

Alfredo Berruti

Editta Baldini, MD

Giuseppe Lo Russo, MD PhD

claudia Maria Regina Bareggi, MD

Elisa Roca

Luca Toschi, MD

Dariusz Kowalski, MD

Jaroslaw Kolb-Sielecki

Marek Jasiowka, MD

Marcin Kowalski, MD

Renata Surma-Wlodarczyk, MD

Rodryg Ramlau

Adam Antczak

Raquel Marse, MD

Margarita Amenedo Gancedo

Bartomeu Massuti Sureda, MD

Marta Gonzalez Cordero

Enriqueta Felip, MD PhD

Alfredo Sanchez Hernandez

Begona Campos Balea, MD

Manuel Domine Gomez, MD

Silvia Catot Tort, MD

Maria Carmen Areses Manrique

Hugo Aranasz, MD

Oscar Juan Vidal, MD

Solange Peters, MD PhD

Alessandra Curioni-Fontecedro

Sebastian Kraus, MD

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.

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.

Single Group Assignment Part 1 sequential dose escalation. Part 2 randomized double-blind.

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.

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

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

Incidence of adverse events (AEs), serious adverse events, AEs leading to discontinuation, deaths, and clinically significant laboratory abnormalities.

Time from first dose to the date of first documented radiologic progression per RECIST v1.1 or time of death, which ever comes first

Proportion of participants with a best overall response of complete (CR) or partial (PR) response as assessed by RECIST v1.1

Time from first CR or PR to first documented progression or death from any cause, per RECIST v1.1

Change in sum of size of target tumors from baseline, per RECIST v1.1

Proportion of participants with CR, PR, or stable disease (SD) sustained over at least 2 consecutive tumor assessments, per RECIST v1.1

Time from randomization to date of death due to any cause.

Time to definitive deterioration in global health status/quality of life

Cmax for inupadenant and its primary metabolite as observed by assessment of concentration-time profile

Tmax for inupadenant and its primary metabolite as observed by assessment of concentration-time profile

T-1/2 for inupadenant and its primary metabolite

AUC from Time 0 extrapolated to infinity for inupadenant and its primary metabolite

iTeos Belgium SA

Skin and Connective Tissue Diseases

Melanoma

Head and Neck Neoplasms

Antibodies

Antibodies, Monoclonal

Dostarlimab

Immunoglobulins

Participants will receive EOS-448 and pembrolizumab at every cycle

Participants will receive EOS-448 at every cycle and inupadenant on an ongoing basis

Participants will receive EOS-448 and dostarlimab at every cycle

Participants will receive dostarlimab at every cycle and inupadenant on an ongoing basis

Participants will receive EOS-448 and dostarlimab at every cycle and inupadenant on an ongoing basis

Participants with 1L mNSCLC will receive EOS-448 and dostarlimab and chemotherapies at every cycle

Participants with 1L mHNSCC CPS ≥ 20 will receive EOS-448 and dostarlimab at every cycle

Participants with 1L mHNSCC 1 \< CPS \< 20 will receive EOS-448 and dostarlimab at every cycle

EOS-448

pembrolizumab

SOC chemotherapies

Clinical Trial Unit

Clinical Trial Unit Unit

Clinical Trials Unit

Iteos Clinical Trials

This is a multicenter, open-label, phase I/II basket study, evaluating the safety, tolerability, RP2D, pharmacokinetics, pharmacodynamics and antitumor activity of EOS-448 (also known as GSK4428859A or belrestotug) combined with standard of care and/or with investigational therapies in participants with advanced solid tumors.

The combinations evaluated will be:

* EOS-448 combined with pembrolizumab, an anti-PD-1 antibody
* EOS-448 combined with inupadenant an investigational adenosine A2A receptor antagonist
* EOS-448 combined with dostarlimab an anti-PD-1 antibody
* inupadenant combined with dostarlimab
* EOS-448 combined with inupadenant and dostarlimab
* EOS-448 combined with dostarlimab and standard of care chemotherapies in participants with NSCLC

Study of EOS-448 With Standard of Care and/or Investigational Therapies in Participants With Advanced Solid Tumors

A Multicenter, Open-Label, Phase I/II Study of EOS884448 (EOS-448) in Combination With Standard of Care and/or Investigational Therapies in Participants With Advanced Solid Tumors

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
New Formulation Study of Inupadenant (EOS100850) in Patients With Cancer	NCT05117177	Solid Tumor, Ad...	Inupadenant	18 Years -	iTeos Therapeutics
First-in-Human Study of EOS100850 in Patients With Cancer	NCT03873883	Solid Tumor, Ad...	EOS100850 Pembrolizumab Chemotherapy	18 Years -	iTeos Therapeutics
Study of Inupadenant (EOS100850) With Chemotherapy as Second Line Treatment for Nonsquamous Non-small Cell Lung Cancer	NCT05403385	Metastatic NSCL... Stage III NSCLC	inupadenant Placebo Carboplatin Pemetrexed	18 Years -	iTeos Therapeutics
Study of EOS-448 With Standard of Care and/or Investigational Therapies in Participants With Advanced Solid Tumors	NCT05060432	Advanced Cancer Lung Cancer Head and Neck C... Melanoma	EOS-448 pembrolizumab inupadenant Dostarlimab SOC chemotherap...	18 Years -	iTeos Therapeutics
Study of Inupadenant (EOS100850) With Chemotherapy as Second Line Treatment for Nonsquamous Non-small Cell Lung Cancer	NCT05403385	Metastatic NSCL... Stage III NSCLC	inupadenant Placebo Carboplatin Pemetrexed	18 Years -	iTeos Therapeutics

Spots Global Cancer Trial Database for inupadenant

Every month we try and update this database with for inupadenant cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for inupadenant

Every month we try and update this database with for inupadenant cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for inupadenant cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.