Inupadenant + Chemotherapy for Non-Small Cell Lung Cancer

Recruiting at68 trial locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: iTeos Therapeutics

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: CNS metastases, EGFR mutation, others

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This trial tests a new drug, inupadenant, combined with standard chemotherapy drugs in lung cancer patients who did not respond to their first treatment. The goal is to see if this combination works better than the standard treatment alone.

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.

How does the drug Inupadenant combined with chemotherapy differ from other treatments for non-small cell lung cancer?

Inupadenant combined with chemotherapy is unique because it potentially offers a novel mechanism of action compared to standard platinum-based chemotherapy regimens, which are known for their antitumor activity and toxicity. This combination may provide a new option for patients, especially if it demonstrates synergistic effects with chemotherapy agents like paclitaxel, which is already used in NSCLC treatment. ^{1 2 3 4 5}

Research Team

Iteos Clinical Trials

Principal Investigator

iTeos Belgium SA

Eligibility Criteria

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

Trial Timeline

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

Treatment Details

Interventions

• Inupadenant (Adenosine Receptor Antagonist)

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

References

1. Japan pubmed.ncbi.nlm.nih.gov

[Lung cancer]. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Irinotecan in cancers of the lung and cervix. [2019]

3. Switzerland pubmed.ncbi.nlm.nih.gov

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

4. Germany pubmed.ncbi.nlm.nih.gov

Phase II study of nedaplatin and irinotecan as adjuvant chemotherapy for completely resected non-small cell lung cancer. [2019]

5. United States pubmed.ncbi.nlm.nih.gov

Phase II study of paclitaxel and cisplatin in patients with non-small cell lung cancer. [2015]