Inupadenant + Chemotherapy for Non-Small Cell Lung Cancer

Not currently recruiting at 72 trial locations

Overseen By iTeos Belgium SA

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: iTeos Therapeutics

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: CNS metastases, EGFR mutation, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 24 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug, inupadenant, for individuals with non-small cell lung cancer that has spread or cannot be surgically removed. Researchers aim to determine the optimal dose of inupadenant when combined with standard chemotherapy drugs, carboplatin and pemetrexed, and assess its effectiveness compared to the usual treatment alone. Eligible participants should have non-small cell lung cancer that has progressed after prior treatment with certain immune therapy drugs (anti-PD(L)1 treatment). The trial seeks to determine if the new combination can provide better outcomes for patients. As a Phase 2 trial, the research focuses on evaluating the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you are on medications for autoimmune diseases or require systemic immunosuppressants, you may not be eligible to participate.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that inupadenant was safe in earlier studies. Patients who took inupadenant experienced stable disease, meaning their cancer did not worsen, for over six months. This suggests that the treatment is well-tolerated by some patients with advanced solid tumors.

When combined with the chemotherapy drugs carboplatin and pemetrexed, inupadenant achieved a 63.9% overall response rate, indicating that most patients saw a reduction in the size or spread of their cancer. The combination also resulted in a median progression-free survival of 7.7 months, meaning patients lived that long without their cancer worsening.

The current study aims to find the best dose of inupadenant when used with these chemotherapy drugs, closely monitoring safety. While the study continues to gather more information about side effects, earlier findings suggest that the treatment is generally safe for humans. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for non-small cell lung cancer?

Most treatments for non-small cell lung cancer, like chemotherapy, target rapidly dividing cells, but they often affect healthy cells too. Inupadenant stands out because it works differently, targeting the adenosine A2A receptor in the tumor microenvironment. This receptor can suppress the immune response, so by blocking it, Inupadenant aims to help the immune system better attack cancer cells. Researchers are excited because this approach could potentially enhance the effectiveness of chemotherapy, offering a more targeted and less toxic treatment option.

What evidence suggests that inupadenant combined with chemotherapy could be effective for non-small cell lung cancer?

Research has shown that inupadenant may help treat non-small cell lung cancer. In this trial, participants will receive different treatments. In Part 1, participants will receive inupadenant at one or more dose levels to determine the recommended Phase 2 dose. In Part 2, some participants will receive inupadenant combined with carboplatin and pemetrexed, while others will receive a matched placebo combined with carboplatin and pemetrexed. Previous studies found that some patients with advanced solid tumors experienced stable disease, and a few had lasting improvements for over six months. Inupadenant blocks A2A receptors on immune cells in tumors, counteracting substances in the tumor that weaken the immune system. This action may allow the body to fight cancer more effectively. Additionally, the pathway targeted by inupadenant has shown promising results in lung cancer patients by enhancing the immune system's response to tumors. ^{2 3 4 5 6}

Who Is on the Research Team?

Iteos Clinical Trials

Principal Investigator

iTeos Belgium SA

Are You a Good Fit for This Trial?

This trial is for adults with advanced non-squamous Non-Small Cell Lung Cancer (NSCLC) that's worsened after first-line treatments. They must have a performance status indicating they can care for themselves, measurable disease progression, and no major organ dysfunction. Excluded are those with untreated brain metastases, active lung or autoimmune diseases, certain other cancers or infections, recent surgeries, significant heart issues, or women who are pregnant/breastfeeding.

Inclusion Criteria

My advanced lung cancer's PD-L1 status is known.

I can provide a biopsy taken within the last 2 years or a new one.

My cancer has returned or worsened after treatment with anti-PD-(L)1 therapy.

Exclusion Criteria

I have or had lung inflammation or scarring, but only mild from previous treatment.

I have serious heart problems that are not under control.

Pregnant or breast-feeding

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose-finding

Open-label, dose-finding design to determine the recommended Phase 2 dose of inupadenant combined with carboplatin and pemetrexed

3 weeks (1 cycle)

Treatment

Participants receive inupadenant or placebo in combination with carboplatin and pemetrexed

Up to 24 months

Regular visits for imaging, safety, and pharmacokinetic assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Inupadenant

Trial Overview

The study has two parts: the first part finds the best dose of Inupadenant combined with chemotherapy drugs Carboplatin and Pemetrexed. The second part tests how well Inupadenant works compared to a placebo when both are added to the same chemo regimen in patients whose cancer progressed after initial treatment.

How Is the Trial Designed?

Group I: Part 2, active treatment Experimental Treatment 3 Interventions

Treatment with inupadenant combined with carboplatin and pemetrexed

Group II: Part 1, open label Experimental Treatment 3 Interventions

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

Group III: Part 2, placebo Placebo Group 3 Interventions

Treatment with matched placebo combined with carboplatin and pemetrexed

Who Is Running the Clinical Trial?

iTeos Therapeutics

Lead Sponsor

Trials

11

Recruited

2,500+

iTeos Belgium SA

Industry Sponsor

Trials

9

Recruited

950+

Published Research Related to This Trial

Novel chemotherapeutic agents for lung cancer are being developed with the goal of having unique mechanisms of action and better safety profiles compared to traditional cisplatin-based treatments.

These new agents, including paclitaxel, docetaxel, and gemcitabine, are expected to show significant efficacy, with response rates over 20% and improved survival rates, while also potentially enhancing the effectiveness of existing therapies like cisplatin and radiation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Lung cancer]. Furuse, K.[2022]

In a phase II study involving 39 patients with completely resected stage II or III non-small cell lung cancer, 92.3% completed four cycles of adjuvant chemotherapy with nedaplatin and irinotecan, indicating high tolerability of this regimen.

The treatment resulted in a median disease-free survival of 49.4 months and a 5-year overall survival rate of 69.8%, suggesting that nedaplatin and irinotecan are effective options for improving outcomes in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of nedaplatin and irinotecan as adjuvant chemotherapy for completely resected non-small cell lung cancer. Murakami, S., Saito, H., Kondo, T., et al.[2019]

In a study involving 75 chemotherapy-naive patients with stage IIIB and IV non-small cell lung cancer, the combination of paclitaxel and cisplatin showed promising efficacy, with a 37% partial remission rate and a 5% complete remission rate.

The treatment was generally well tolerated, with moderate hematologic toxicities; 37% of treatment cycles experienced grade 3 or 4 neutropenia, but severe thrombocytopenia was rare, occurring in only 2% of cycles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of paclitaxel and cisplatin in patients with non-small cell lung cancer. von Pawel, J., Wagner, H., Niederle, N., et al.[2015]

Irinotecan shows promising efficacy as a treatment for advanced non-small cell lung cancer (NSCLC), with response rates between 13-32% as a single agent and up to 75% when combined with cisplatin, outperforming older treatments.

In small cell lung cancer (SCLC), irinotecan also demonstrates significant activity, achieving response rates of 16-47% alone and up to 79% in combination with cisplatin or etoposide, although it is associated with dose-limiting toxicities like neutropenia and diarrhea.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Irinotecan in cancers of the lung and cervix. Sandler, A., van Oosterom, AT.[2019]

The study investigates a combination treatment of oral topotecan and intravenous paclitaxel for advanced non-small-cell lung cancer (NSCLC), aiming to enhance antitumor activity compared to standard platinum-based chemotherapy.

Preliminary data on the maximum tolerated dose of oral topotecan (1.0-1.5 mg/m²/day for 5 days) alongside paclitaxel (175 mg/m² on day 1) will provide insights into the feasibility and tolerability of this multidrug regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Feasibility of oral topotecan plus intravenous paclitaxel in advanced non-small-cell lung cancer. Eckardt, JR.[2017]

Citations

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clinicaltrials.gov/study/NCT05403385

Study of Inupadenant (EOS100850) With Chemotherapy as ...

The study will first determine the optimal dose of inupadenant to be given in combination with carboplatin and pemetrexed to patients that progressed after ...

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Durable responses and stable disease greater than six months were observed in five patients with advanced solid tumors…stable disease in a patient with non- ...

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Phase 1 trial of the adenosine A2A receptor antagonist ...

Blocking A2A receptors, predominantly expressed on tumor-infiltrating immune cells, can reverse the immunosuppressive effect of adenosine.

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Study of Inupadenant (EOS100850) With Chemotherapy as ...

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 ...

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The Adenosinergic Pathway in Non-Small Cell Lung Cancer

These molecules restore the host's immune response against tumor cells and led to impressive results in non-small cell lung cancer patients.

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clinicaltrials.gov/study/NCT05403385

NCT05403385 | Study of Inupadenant (EOS100850) With ...

The study will first determine the optimal dose of inupadenant to be given in combination with carboplatin and pemetrexed to patients that progressed after ...