JNJ-86974680 + Radiation Therapy + Cetrelimab for Non-Small Cell Lung Cancer

Recruiting at 17 trial locations

Overseen By Study Contact

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Johnson & Johnson Enterprise Innovation Inc.

Must be taking: Anti-PD-1, PD-L1, Platinum-based

Disqualifiers: CNS disease, Autoimmune, Infection, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

126 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment for individuals with advanced non-small cell lung cancer (NSCLC). Researchers are testing a combination of two treatments, JNJ-86974680 (an A2AR antagonist) and cetrelimab, along with radiation therapy, to determine a safe dose for future studies. Ideal candidates have stage IIIB-IV NSCLC and have either exhausted all targeted therapies or have no targetable mutations. Participants should have received specific therapies like anti-PD-1/PD-L1 and platinum-based chemotherapy, unless they are treatment-naïve. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the chance to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

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

Research has shown that JNJ-86974680 has been tested alone and with cetrelimab to assess safety. Early results suggest these treatments are generally safe and well-tolerated. Studies have found that JNJ-86974680 can be administered in doses up to 120 mg without causing serious side effects, known as dose-limiting toxicity. Most participants did not experience severe negative effects.

Cetrelimab is also being tested with other treatments, such as radiation. The current focus is on determining the right dose and observing responses to the combination. Although these treatments are still in early testing stages, previous studies have not identified major safety issues. This is encouraging for those considering joining the trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about JNJ-86974680 with cetrelimab for non-small cell lung cancer because these treatments offer a novel approach compared to current standards like chemotherapy and targeted therapies. JNJ-86974680 is a new drug that, when paired with cetrelimab, targets specific pathways to enhance the body's immune response against cancer cells. Unlike traditional treatments that may not specifically boost immune activity, this combination aims to work synergistically with radiation therapy to potentially improve outcomes by attacking the cancer more effectively. This innovative strategy could lead to more precise and powerful treatment options for patients.

What evidence suggests that this trial's treatments could be effective for non-small cell lung cancer?

Research shows that JNJ-86974680 may help treat cancer by blocking a receptor called A2aR, which usually helps cancer evade the immune system. In lab studies, JNJ-86974680 successfully blocked this receptor, potentially enabling the immune system to attack cancer cells more effectively. Early results from human studies indicate that this drug, both alone and with another drug called cetrelimab, is safe for people without causing severe side effects. Cetrelimab is a treatment that helps the immune system identify and fight cancer cells. In this trial, participants will receive JNJ-86974680 and cetrelimab, with some also receiving radiation therapy, to test if this combination can improve outcomes for patients with non-small cell lung cancer. Although still in early stages, these findings are promising for the potential success of this combination. ^{1 2 3 4 5}

Who Is on the Research Team?

Johnson & Johnson Enterprise Innovation, Inc Clinical Trial

Principal Investigator

Johnson & Johnson Enterprise Innovation Inc.

Are You a Good Fit for This Trial?

This trial is for individuals with advanced non-small cell lung cancer who have already tried anti-PD-1/PD-L1 therapy and chemotherapy but their cancer has progressed. They must have good liver function, at least 3 lesions visible on scans, and be able to provide a recent tumor sample. People with active autoimmune diseases, organ transplants, untreated brain metastases or certain genetic mutations treatable by approved drugs cannot join.

Inclusion Criteria

My liver functions are within the required limits for the trial.

I have advanced lung cancer and my previous treatments with specific immune therapies and chemotherapy have not worked.

My NSCLC has a specific mutation and I've tried all approved treatments without success.

Exclusion Criteria

I have not taken immunosuppressive drugs for an autoimmune disease in the last year.

I haven't taken any infection-fighting drugs in the last week.

I have had a solid organ or bone marrow transplant.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Part 1

Participants receive JNJ-86974680 alone in 4 cohorts and then with cetrelimab

Varies by cohort

Treatment Part 2

Participants receive JNJ-86974680 with cetrelimab and radiation therapy

Varies by cohort

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 2 years 5 months

What Are the Treatments Tested in This Trial?

Interventions

• Cetrelimab
• JNJ-86974680
• Radiation Therapy

Trial Overview The study is testing the safety and tolerability of JNJ-86974680 when combined with cetrelimab (another drug) and radiation therapy in patients. The goal is to find the right doses of JNJ-86974680 that can be used safely for further research.

How Is the Trial Designed?

Group I: Part 2: JNJ-86974680+Cetrelimab+Radiation Therapy (RT) Experimental Treatment 3 Interventions

Part 2 will consist of 3 cohorts (A, B and C) and participants will receive treatment with the selected dose of JNJ-86974680 in combination with cetrelimab from part 1, in conjunction with radiation.

Group II: Part 1: JNJ-86974680+Cetrelimab Experimental Treatment 2 Interventions

Participants will receive JNJ-86974680 alone (dose 1, dose 2, dose 3, and dose 4) daily in 4 cohorts and then along with a set dose of cetrelimab.

Who Is Running the Clinical Trial?

Johnson & Johnson Enterprise Innovation Inc.

Lead Sponsor

Trials

5

Recruited

910+

Published Research Related to This Trial

In a phase II trial involving 30 patients with stage III nonsmall cell lung cancer, the combination of intensity-modulated radiation therapy (IMRT) and cetuximab resulted in a 63% overall response rate, indicating significant efficacy in treating this patient population.

The treatment was well-tolerated, with only mild toxicity observed, including a low incidence of grade 3 pneumonitis (3.3%) and overall acute toxicity (36.7%), making it a safe option for elderly patients with multiple health issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined treatment of nonsmall cell lung cancer NSCLC stage III with intensity-modulated RT radiotherapy and cetuximab: the NEAR trial. Jensen, AD., Münter, MW., Bischoff, HG., et al.[2015]

Concurrent immunoradiotherapy, combining immune checkpoint inhibitors with radiotherapy, showed a 30% overall response rate in 16 patients with metastatic melanoma who had progressed on nivolumab, with a notable 68.8% response rate in lesions within the radiation fields.

Nivolumab combined with radiotherapy demonstrated a 100% response rate inside the radiation fields, suggesting it may be more effective than ipilimumab in this setting, although some patients experienced grade 3 adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of concurrent immunoradiotherapy in patients with metastatic melanoma after progression on nivolumab. Nomura, M., Otsuka, A., Yoshimura, M., et al.[2019]

In a phase 2 trial involving 90 patients with non-small-cell lung cancer resistant to PD-1/PD-L1 therapy, the combination of PD-L1 (durvalumab) and CTLA-4 (tremelimumab) with radiotherapy did not show improved overall response rates compared to the therapy alone, leading to the trial's early termination due to futility.

The most common serious adverse events were manageable, but one patient in the low-dose radiotherapy group died from respiratory failure potentially related to the treatment, highlighting the need for careful monitoring in future studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab plus tremelimumab alone or in combination with low-dose or hypofractionated radiotherapy in metastatic non-small-cell lung cancer refractory to previous PD(L)-1 therapy: an open-label, multicentre, randomised, phase 2 trial. Schoenfeld, JD., Giobbie-Hurder, A., Ranasinghe, S., et al.[2023]

In a phase III study involving 479 patients with metastatic non-small-cell lung cancer (NSCLC), sugemalimab combined with chemotherapy significantly improved progression-free survival (PFS) compared to placebo plus chemotherapy.

The interim analysis also showed that patients receiving sugemalimab had a median overall survival (OS) of 25.4 months, compared to 16.9 months for those on placebo, indicating that sugemalimab is an effective first-line treatment option for metastatic NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Interim survival analysis of the randomized phase III GEMSTONE-302 trial: sugemalimab or placebo plus chemotherapy as first-line treatment for metastatic NSCLC. Zhou, C., Wang, Z., Sun, M., et al.[2023]

In a study involving 449 patients with advanced non-small-cell lung cancer (NSCLC), pembrolizumab showed overall response rates of 15% at 2 mg/kg, 25% at 10 mg/kg every 3 weeks, and 21% at 10 mg/kg every 2 weeks, indicating that the 2 mg/kg dose may be sufficient for efficacy.

The analysis revealed no significant relationship between the dose of pembrolizumab and its efficacy or safety, suggesting that the lower dose of 2 mg/kg every 3 weeks is effective and safe for patients with previously treated advanced NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systematic evaluation of pembrolizumab dosing in patients with advanced non-small-cell lung cancer. Chatterjee, M., Turner, DC., Felip, E., et al.[2022]

Cetuximab, when combined with cisplatin and vinorelbine, significantly improved survival rates in patients with advanced non-small cell lung cancer (NSCLC) compared to chemotherapy alone, as shown in the phase III FLEX trial.

High expression of the epidermal growth factor receptor (EGFR) in tumor cells is a predictor of the survival benefit from cetuximab, while KRAS mutations do not provide predictive value, highlighting the importance of EGFR status in treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

EGFR-directed monoclonal antibodies in non-small cell lung cancer. Pirker, R.[2022]

In a study involving 51 patients with advanced non-small-cell lung cancer (NSCLC) who had previously undergone multiple treatments, the combination of pembrolizumab and ipilimumab demonstrated an objective response rate of 30%, indicating some level of antitumor activity.

While the combination therapy showed potential benefits, it also resulted in significant toxicity, with 64% of patients experiencing treatment-related adverse events, highlighting the need for careful monitoring and management of side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab in combination with ipilimumab as second-line or later therapy for advanced non-small-cell lung cancer: KEYNOTE-021 cohorts D and H. Gubens, MA., Sequist, LV., Stevenson, JP., et al.[2020]

Combination immunotherapies, such as PD-1 and CTLA-4 blockade, show promising results in treating non-small cell lung cancer (NSCLC), potentially improving outcomes compared to single-agent therapies.

Early clinical trials indicate that these combination therapies can be administered safely without significantly increasing toxicity, but further research is necessary to assess long-term safety, efficacy, and optimal patient selection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination Immunotherapy in Non-small Cell Lung Cancer. Marmarelis, ME., Aggarwal, C.[2022]

In a multicenter phase II study involving 35 Japanese patients with advanced squamous non-small cell lung cancer (NSCLC), nivolumab demonstrated an overall response rate (ORR) of 25.7%, indicating its effectiveness after platinum-based chemotherapy.

Nivolumab was well tolerated, with 68.6% of patients experiencing treatment-related adverse events, most of which were manageable, suggesting a favorable safety profile for this treatment in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of nivolumab in Japanese patients with advanced or recurrent squamous non-small cell lung cancer. Hida, T., Nishio, M., Nogami, N., et al.[2022]

In a study of 80 patients with locally advanced non-small cell lung cancer (NSCLC), combining Camrelizumab with intensity modulated radiation therapy (IMRT) resulted in a significantly higher treatment efficacy of 70% compared to 47.5% in the control group receiving only IMRT (p=0.03).

The combination therapy also led to notable improvements in immune markers (CD3+, CD4+, CD4+/CD8+) and physical status without a significant increase in adverse drug reactions (50% in the experimental group vs. 37.5% in the control group, p=0.26), indicating that the treatment is both effective and safe.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of Intensity Modulated Radiotherapy (IMRT) on the immunity, physical status and clinical effect of locally advanced NSCLC patients. Xu, JK.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06116786

NCT06116786 | A Study of JNJ-86974680 in Participants ... The purpose of this study is to determine a safe and tolerable dose(s) of JNJ-86974680 for further research in combination with cetrelimab and radiation therapy ...

2. aacrjournals.org aacrjournals.org/cancerres/article/85/8_Supplement_2/CT137/761343/Abstract-CT137-Initial-results-from-a-phase-1

Abstract CT137: Initial results from a phase 1 study of an A2a ... A 2-part, first-in-human Phase 1 study, evaluating the safety, pharmacokinetics, and preliminary efficacy of JNJ-86974680 as a monotherapy, and in combination ...

3. jnjmedicalconnect.com jnjmedicalconnect.com/media/attestation/congresses/oncology/2025/aacr/initial-results-from-a-phase-1-study-of-an-a2a-receptor-antagonist-administered-as-monotherapy-and-i.pdf

initial-results-from-a-phase-1-study-of-an-a2a-receptor- ... JNJ-4680 demonstrates potent in vitro inhibition of A2aR at high concentrations of adenosine. • JNJ-4680 was tolerable as monotherapy, and in combination with ...

4. cancer.columbia.edu cancer.columbia.edu/cancer-types-care/clinical-trials/find-clinical-trial/phase-1-study-jnj-86974680-a2a-receptor-antagonist-administered-asmonotherapy-and-combination-cetrelimab-and-radiotherapy-advanced-nonsmallcell-lung-cancer

A phase 1 study of JNJ-86974680, an A2a receptor antagonist ... The purpose of this study is to find out if JNJ-86974680 taken by itself or together with Cetrelimab and radiotherapy can cause side effects.

5. jeffersonhealth.org jeffersonhealth.org/clinical-specialties/cancer/clinical-trials/37384

Clinical Trial The purpose of this study is to determine a safe and tolerable dose(s) of JNJ-86974680 for further research in combination with cetrelimab and radiation therapy ...