Anti-PD-1 Therapy for Advanced Cancers

Recruiting at 133 trial locations

Overseen By Study Contact

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Janssen Research & Development, LLC

Must not be taking: PD-1/PD-L1/PD-L2 antibodies

Disqualifiers: Uncontrolled illness, Prior PD-1/PD-L1, others

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

Compensation: Varies

Number of Visits: Unknown

413 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that you stop any local or systemic anti-cancer treatments at least 14 days before starting the study drug, with a maximum of 28 days without these treatments. Other medications are not specifically mentioned, so it's best to discuss your current medications with the trial team.

What data supports the effectiveness of the drug JNJ-63723283 for advanced cancers?

Research shows that PD-1 inhibitors, like JNJ-63723283, have been effective in treating various advanced cancers by improving survival rates. Similar drugs, such as nivolumab and pembrolizumab, have shown positive results in clinical trials, suggesting potential benefits for JNJ-63723283 as well. ^{1 2 3 4 5}

Is anti-PD-1 therapy generally safe for humans?

Anti-PD-1 therapies, including JNJ-63723283, have been shown to have a manageable safety profile, meaning they are generally safe for outpatient use. They can cause some side effects, but these are typically manageable with proper care. ^{1 6 7 8 9}

How is the drug JNJ-63723283 different from other treatments for advanced cancers?

JNJ-63723283, also known as cetrelimab, is a monoclonal antibody that targets PD-1, a protein that tumors use to hide from the immune system. This drug is unique because it is specifically designed to block PD-1, potentially allowing the immune system to better recognize and attack cancer cells, which may offer a new option for patients with advanced cancers. ^{1 2 10 11 12}

What is the purpose of this trial?

The Primary purpose of this study is to identify the recommended Phase 2 dose \[RP2D(s)\] for JNJ-63723283 in Part 1, to assess the anti-tumor activity of JNJ-63723283 at the RP2D(s) in participants with selected advanced cancers including non-small-cell lung cancer (NSCLC), melanoma, renal, bladder, small-cell lung cancer (SCLC), gastric/esophageal cancer, and high-level microsatellite instability (MSI-H) or mismatch repair-deficient (dMMR) colorectal cancer (CRC) in Part 2, to determine one or more additional RP2Ds in Parts 3 and 4.

Research Team

Janssen Research & Development, LLC Clinical Trial

Principal Investigator

Janssen Research & Development, LLC

Eligibility Criteria

This trial is for adults with certain advanced cancers, including lung, melanoma, renal, bladder, and colorectal cancers. Participants must be in good physical condition (ECOG status 0 or 1), have normal thyroid function, not be pregnant or breastfeeding, and agree to study restrictions. Tissue samples are required for some parts of the study.

Inclusion Criteria

My cancer can be measured or evaluated.

I am a woman who can have children and my pregnancy test is negative.

I am fully active or restricted in physically strenuous activity but can do light work.

Exclusion Criteria

I have been treated with drugs targeting PD-1, PD-L1, or PD-L2.

I do not have any severe ongoing illnesses that would interfere with the study.

I haven't had cancer treatment or investigational drugs in the last 14 days to 28 days.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation (Part 1)

Participants receive JNJ-63723283 at a starting dose of 80 mg IV every 2 weeks, with dose escalation following a modified Continual Reassessment Method (mCRM)

Variable, based on dose escalation

Treatment (Part 2)

Participants receive JNJ-63723283 at the recommended Phase 2 dose (RP2D) determined in Part 1

Up to 2 years 6 months

Pharmacokinetic and Safety Evaluation (Part 3)

Participants receive JNJ-63723283 to evaluate pharmacokinetic (PK), pharmacodynamic (PD), and safety

Up to 2 years 6 months

Dose Confirmation (Part 4)

Participants receive JNJ-63723283 at the dose level determined in Part 3, with additional cohorts possibly enrolled

Up to 2 years 6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• JNJ-63723283

Trial Overview The trial is testing JNJ-63723283's safety and effectiveness at different doses in treating various advanced cancers. It aims to find the best dose for Phase 2 trials and see how well it works against specific cancer types.

Participant Groups

Group I: JNJ-63723283 Experimental Treatment 1 Intervention

In Part 1, the first cohort will receive JNJ-63723283 at a starting dose of 80 milligram (mg), intravenous (IV) every 2 weeks. JNJ-63723283 doses will be escalated following a modified Continual Reassessment Method (mCRM). Multiple doses, dose administration routes (subcutaneous \[SC\] or IV), and dose schedules may be explored. In Part 2, participants will receive JNJ-63723283 at the recommended Phase 2 dose (RP2D) determined in Part 1. In Part 3, participants will receive JNJ-63723283 to evaluate pharmacokinetic (PK), pharmacodynamic (PD) and safety. In Part 4, participants will receive JNJ-63723283 at the dose level determined in Part 3. Additional cohorts may be enrolled in Part 4.

Who Is Running the Clinical Trial?

Janssen Research & Development, LLC

Lead Sponsor

Trials

1,022

Recruited

6,408,000+

Giacomo Salvadore

Janssen Research & Development, LLC

Chief Medical Officer since 2023

MD from the University of Rome, Tor Vergata

Ricardo Attar

Janssen Research & Development, LLC

Chief Executive Officer since 2008

PhD in Molecular Biology from the University of Buenos Aires

Findings from Research

Cetrelimab, a PD-1 inhibitor, was found to have a manageable safety profile in patients with advanced solid tumors, with 53.9% experiencing grade ≥3 adverse events, and 35.3% having immune-related adverse events.

In terms of efficacy, cetrelimab showed an overall response rate of 18.6% across various tumor types, with higher rates in specific cancers like non-small-cell lung cancer (34.3%) and melanoma (28.0%), indicating its potential as a treatment option for these conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-in-human, open-label, phase 1/2 study of the monoclonal antibody programmed cell death protein-1 (PD-1) inhibitor cetrelimab (JNJ-63723283) in patients with advanced cancers. Felip, E., Moreno, V., Morgensztern, D., et al.[2022]

In the JAVELIN Lung 100 trial involving 1214 patients with advanced NSCLC, avelumab showed longer median progression-free survival (PFS) compared to platinum-based chemotherapy (8.4 months vs. 5.6 months), indicating its potential efficacy as a first-line treatment.

Although avelumab demonstrated longer median overall survival (OS) compared to chemotherapy (20.1 months vs. 14.9 months), the differences were not statistically significant, suggesting that while avelumab may be beneficial, it did not meet the primary objective of the trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Avelumab Versus Platinum-Based Doublet Chemotherapy as First-Line Treatment for Patients With High-Expression Programmed Death-Ligand 1-Positive Metastatic NSCLC: Primary Analysis From the Phase 3 JAVELIN Lung 100 Trial. Reck, M., Barlesi, F., Yang, JC., et al.[2023]

In a study of 90 patients with advanced solid tumors treated with PD-1/PD-L1 inhibitors, the objective response rate was 25.6%, with a median progression-free survival of 5.5 months and median overall survival of 16.9 months, indicating promising efficacy.

Clinical factors such as ECOG performance status, smoking status, liver metastasis, and neutrophil-to-lymphocyte ratio were found to significantly influence progression-free survival, while liver metastasis and lactate dehydrogenase levels were linked to overall survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical observation of the efficacy of PD-1/PD-L1 inhibitors in the treatment of patients with advanced solid tumors. Wang, M., Zhen, H., Jiang, X., et al.[2021]

In a study of 66 patients with invasive primary cutaneous melanomas, PD-L1 expression was found in 21% of samples and was significantly associated with increased melanoma thickness and nodular-type melanoma, suggesting that PD-L1 could be a useful biomarker for this type of cancer.

Nodular-type melanoma was 6.48 times more likely to express PD-L1 compared to other types, indicating that patients with this melanoma subtype may benefit from adjuvant immunotherapy targeting PD-L1.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nodular primary cutaneous melanoma is associated with PD-L1 expression. Giavina-Bianchi, M., Giavina-Bianchi, P., Sotto, MN., et al.[2023]

In a four-year study of 80 patients with non-small cell lung cancer treated with anti-PD-1 and anti-PD-L1 therapies, significant overall survival rates were observed, particularly with nivolumab and pembrolizumab, showing 79.7% survival at 6 months and 100% at first-line treatment for pembrolizumab.

Adverse events were common, occurring in over 84% of patients, with fatigue and respiratory issues being the most reported, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical efficacy and safety of anti PD-1/PD-L1 antibodies as monotherapy in patients with non-small-cell lung cancer. Zayas-Soriano, M., Bonete-Sánchez, M., Campillo-López, J., et al.[2021]

Immune checkpoint antibodies targeting the PD-1/PD-L1 pathway have shown significant antitumor activity and have been approved for use as single-agent therapies in metastatic malignant melanoma and nonsmall-cell lung cancer.

Understanding the toxicities associated with PD-1/PD-L1 blockade and having effective management strategies is crucial for maximizing both the safety and efficacy of these treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toxicities of the anti-PD-1 and anti-PD-L1 immune checkpoint antibodies. Naidoo, J., Page, DB., Li, BT., et al.[2023]

Blocking the PD-1 pathway with specific drugs has shown clinical effectiveness in treating advanced cancers like melanoma and lung cancer, by enhancing the body's anti-tumor immune response.

These PD-1/PD-L1 blocking drugs have a manageable safety profile, making them suitable for outpatient treatment and potential use in combination therapies, with ongoing research focused on identifying biomarkers for better patient selection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antagonists of PD-1 and PD-L1 in Cancer Treatment. Lipson, EJ., Forde, PM., Hammers, HJ., et al.[2022]

JTX-4014, a new PD-1 targeting antibody, was well tolerated in a trial with 18 patients and did not show new safety concerns compared to existing PD-1 inhibitors, establishing a recommended dose of 500 mg every 3 weeks or 1000 mg every 6 weeks.

The treatment demonstrated clinical activity with a 16.7% overall response rate and a 44.4% disease control rate, particularly in patients with PD-L1 positive tumors, suggesting potential for further development in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I, first-in-human trial of programmed cell death receptor-1 (PD-1) inhibitor, JTX-4014, in adult patients with advanced, refractory, solid tumors. Papadopoulos, KP., Lakhani, N., Falchook, GS., et al.[2021]

In a phase 3 study involving 94 Asian patients with advanced PD-L1-positive gastric/GEJ cancer, pembrolizumab showed similar overall survival (OS) to paclitaxel, with a median OS of 8 months for both treatments, indicating comparable efficacy.

Pembrolizumab had a significantly better safety profile, with only 60% of patients experiencing any-grade treatment-related adverse events compared to 96% for paclitaxel, and fewer severe (grades 3 to 5) events (11% vs. 64%).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab versus paclitaxel for previously treated advanced gastric or gastroesophageal junction cancer (KEYNOTE-063): A randomized, open-label, phase 3 trial in Asian patients. Chung, HC., Kang, YK., Chen, Z., et al.[2022]

References

1. Germany pubmed.ncbi.nlm.nih.gov

First-in-human, open-label, phase 1/2 study of the monoclonal antibody programmed cell death protein-1 (PD-1) inhibitor cetrelimab (JNJ-63723283) in patients with advanced cancers. [2022]

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

Avelumab Versus Platinum-Based Doublet Chemotherapy as First-Line Treatment for Patients With High-Expression Programmed Death-Ligand 1-Positive Metastatic NSCLC: Primary Analysis From the Phase 3 JAVELIN Lung 100 Trial. [2023]

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

A Comparison of Response Patterns for Progression-Free Survival and Overall Survival Following Treatment for Cancer With PD-1 Inhibitors: A Meta-analysis of Correlation and Differences in Effect Sizes. [2020]

4. England pubmed.ncbi.nlm.nih.gov

Clinical observation of the efficacy of PD-1/PD-L1 inhibitors in the treatment of patients with advanced solid tumors. [2021]

5. France pubmed.ncbi.nlm.nih.gov

Nodular primary cutaneous melanoma is associated with PD-L1 expression. [2023]

6. Spain pubmed.ncbi.nlm.nih.gov

Clinical efficacy and safety of anti PD-1/PD-L1 antibodies as monotherapy in patients with non-small-cell lung cancer. [2021]

7. England pubmed.ncbi.nlm.nih.gov

Toxicities of the anti-PD-1 and anti-PD-L1 immune checkpoint antibodies. [2023]

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

Antagonists of PD-1 and PD-L1 in Cancer Treatment. [2022]

9. Germany pubmed.ncbi.nlm.nih.gov

Phase I, first-in-human trial of programmed cell death receptor-1 (PD-1) inhibitor, JTX-4014, in adult patients with advanced, refractory, solid tumors. [2021]

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

CS1003, a novel human and mouse cross-reactive PD-1 monoclonal antibody for cancer therapy. [2022]

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

Pembrolizumab versus paclitaxel for previously treated advanced gastric or gastroesophageal junction cancer (KEYNOTE-063): A randomized, open-label, phase 3 trial in Asian patients. [2022]

12. England pubmed.ncbi.nlm.nih.gov

PD-1/PD-L1 inhibitors. [2022]