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

Recruiting at 12 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

Trial Summary

What is the purpose of this 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.

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.

What data supports the effectiveness of the treatment JNJ-86974680 + Radiation Therapy + Cetrelimab for Non-Small Cell Lung Cancer?

Research suggests that combining immunotherapy drugs with radiotherapy can enhance the body's immune response against tumors in non-small cell lung cancer (NSCLC). Studies have shown that combination therapies, like those involving PD-1 and CTLA-4 inhibitors, can improve outcomes compared to single-agent treatments. ^{1 2 3 4 5}

What makes the treatment with JNJ-86974680, radiation therapy, and Cetrelimab unique for non-small cell lung cancer?

This treatment is unique because it combines JNJ-86974680, an A2AR antagonist that may enhance immune response, with Cetrelimab, an immune checkpoint inhibitor, and radiation therapy, potentially offering a novel approach to boost the body's immune system against non-small cell lung cancer. ^{6 7 8 9 10}

Research Team

Johnson & Johnson Enterprise Innovation, Inc Clinical Trial

Principal Investigator

Johnson & Johnson Enterprise Innovation Inc.

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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]

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]

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]

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]

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]

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]

References

1. England 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. [2023]

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

Combination Immunotherapy in Non-small Cell Lung Cancer. [2022]

3. Ireland 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. [2020]

4. England 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. [2023]

5. England pubmed.ncbi.nlm.nih.gov

Systematic evaluation of pembrolizumab dosing in patients with advanced non-small-cell lung cancer. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of nivolumab in Japanese patients with advanced or recurrent squamous non-small cell lung cancer. [2022]

7. Pakistan pubmed.ncbi.nlm.nih.gov

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

8. United States 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. [2015]

9. France pubmed.ncbi.nlm.nih.gov

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

10. Germany pubmed.ncbi.nlm.nih.gov

Efficacy and safety of concurrent immunoradiotherapy in patients with metastatic melanoma after progression on nivolumab. [2019]