JZP898 + Pembrolizumab for Advanced Cancer

Recruiting at 9 trial locations

Overseen By Clinical Trial Disclosure & Transparency

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Jazz Pharmaceuticals

Must not be taking: Systemic steroids, Immunosuppressive agents

Disqualifiers: CNS tumor, Autoimmune disease, others

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

Compensation: Varies

Number of Visits: Unknown

177 Participants Needed

Trial Summary

What is the purpose of this trial?

This Phase 1 first-in-human study will investigate the safety, tolerability, pharmacokinetics (PK), immunogenicity, and preliminary antitumor activity of JZP898 monotherapy as well as JZP898 in combination with pembrolizumab in adult participants with advanced or metastatic solid tumors.

Will I have to stop taking my current medications?

The trial requires that you stop taking any anticancer therapy at least 4 weeks or 5 half-lives (whichever is shorter) before starting the study drug. Other medications are not specifically mentioned, so it's best to discuss with the trial team.

What data supports the effectiveness of the drug pembrolizumab in treating advanced cancer?

Research shows that pembrolizumab, when used alone or with other drugs, improves survival and response rates in patients with advanced non-small-cell lung cancer and malignant melanoma. This suggests it may be effective in treating other advanced cancers as well. ^{1 2 3 4 5}

Is the combination of JZP898 and Pembrolizumab safe for humans?

Pembrolizumab, also known as KEYTRUDA, has been studied in various cancers and is generally considered safe, but it can cause side effects like fatigue, cough, nausea, and immune-related issues such as lung inflammation and thyroid problems. The safety of JZP898 specifically in combination with Pembrolizumab is not detailed here, so it's important to discuss potential risks with your doctor. ^{3 6 7 8 9}

What makes the drug JZP898 + Pembrolizumab unique for treating advanced cancer?

This treatment combines JZP898 with Pembrolizumab, a drug that helps the immune system fight cancer by blocking a protein called PD-1, which can stop immune cells from attacking cancer cells. The combination aims to enhance the immune response against cancer, potentially offering a new option for patients with advanced cancer. ^{3 4 9 10 11}

Eligibility Criteria

Adults over 18 with advanced or metastatic solid tumors who have tried certain treatments without success can join. They need to be fairly active and healthy (ECOG score of 0-1), not pregnant, willing to use birth control, and able to provide tumor samples. People with severe allergies, recent cancer therapies or surgeries, autoimmune diseases needing steroids, CNS tumors, lung disease requiring steroids, suicidal behavior or significant heart issues cannot participate.

Inclusion Criteria

Additional criteria may apply

My cancer is advanced or has spread to other parts of my body.

I have a solid tumor and no standard treatments are expected to help me.

Exclusion Criteria

You have a history of attempting suicide or have had thoughts of wanting to harm yourself.

I haven't taken any cancer treatments within the last 4 weeks or 5 half-lives, whichever is shorter.

I have side effects from previous treatments that are not severe.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Part A1 Dose Exploration

Monotherapy dose exploration to determine the monotherapy recommended dose and/or maximum tolerated dose (MTD) and safety profile of JZP898

8-12 weeks

Part A2 Dose Exploration

Combination dose exploration of JZP898 plus pembrolizumab to determine the combination recommended dose followed by confirmation of the recommended phase 2 dose (Combination RP2D)

8-12 weeks

Part B Combination Expansion

Combination expansion using a basket design to evaluate clinical antitumor activity and safety profile of JZP898 in combination with pembrolizumab at the Combination RP2D identified in Part A2

16-24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

Treatment Details

Interventions

• JZP898
• Pembrolizumab

Trial Overview The trial is testing JZP898 alone and combined with Pembrolizumab in adults with tough-to-treat cancers. It's a first-in-human study looking at safety and how the body processes these drugs while checking for any signs that they might shrink the tumors.

Participant Groups

Group I: Part B Combination Expansion: JZP898 in combination with pembrolizumab Experimental Treatment 2 Interventions

Group II: Part A2 Dose Exploration: JZP898 in combination with pembrolizumab Experimental Treatment 2 Interventions

Group III: Part A1 Dose Exploration: JZP898 monotherapy Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

Jazz Pharmaceuticals

Lead Sponsor

Trials

252

Recruited

35,100+

Bruce C. Cozadd

Jazz Pharmaceuticals

Chief Executive Officer since 2009

BA in Economics from Yale University, MBA from Stanford University

Dr. Austin

Jazz Pharmaceuticals

Chief Medical Officer since 2023

MD from the Royal College of Surgeons in Ireland

Merck Sharp & Dohme LLC

Industry Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Findings from Research

In the KEYNOTE-024 study involving 305 patients with untreated advanced non-small-cell lung cancer, pembrolizumab significantly improved overall survival (OS) compared to platinum-based chemotherapy, with a median OS of 30.0 months versus 14.2 months for chemotherapy.

Pembrolizumab also had a better safety profile, with fewer treatment-related severe adverse events (31.2% for pembrolizumab vs. 53.3% for chemotherapy), indicating it is a safer option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Updated Analysis of KEYNOTE-024: Pembrolizumab Versus Platinum-Based Chemotherapy for Advanced Non-Small-Cell Lung Cancer With PD-L1 Tumor Proportion Score of 50% or Greater. Reck, M., Rodríguez-Abreu, D., Robinson, AG., et al.[2022]

In a long-term study of 123 patients with advanced nonsquamous NSCLC, the combination of pembrolizumab with pemetrexed-carboplatin significantly improved the objective response rate (58% vs. 33%) and progression-free survival (24.5 months vs. 9.9 months) compared to chemotherapy alone.

Patients who completed 2 years of pembrolizumab treatment had a remarkable 92% survival rate at the data cutoff, indicating a durable clinical benefit, while the safety profile remained manageable with no new safety concerns identified.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-Term Overall Survival From KEYNOTE-021 Cohort G: Pemetrexed and Carboplatin With or Without Pembrolizumab as First-Line Therapy for Advanced Nonsquamous NSCLC. Awad, MM., Gadgeel, SM., Borghaei, H., et al.[2021]

In a phase II trial involving 15 patients with resectable non-small cell lung cancer (NSCLC), neoadjuvant treatment with pembrolizumab showed a major pathologic response in 27% of patients, indicating promising antitumor activity before surgery.

The treatment was found to be feasible and safe, with only 33% of patients experiencing moderate adverse events, and no postoperative mortality, suggesting that pembrolizumab does not compromise surgical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. Eichhorn, F., Klotz, LV., Kriegsmann, M., et al.[2022]

Pembrolizumab (Keytruda) is the first anti-PD-1 therapy approved in the US for treating advanced malignant melanoma, specifically for patients who have progressed after prior treatments.

It is designed to target the PD-1 protein, enhancing the immune system's ability to fight cancer, and is currently under review for approval in the EU.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab: first global approval. Poole, RM.[2021]

The uptake of 89Zr-pembrolizumab, a radiolabeled antibody used in imaging, is correlated with patient survival rates, suggesting it may be a useful biomarker for predicting outcomes in cancer treatment.

Higher levels of 89Zr-pembrolizumab uptake are associated with better treatment responses, indicating its potential role in guiding therapy decisions for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

89Zr-pembrolizumab Uptake Predicts Survival and Immunotherapy Response. [2022]

Pembrolizumab (KEYTRUDA) was approved by the FDA for treating advanced melanoma, showing an overall response rate of 24% in a trial of 89 patients, with 86% of responses lasting at least 6 months.

While there are potential immune-mediated side effects, the benefits of prolonged tumor response durations were deemed to outweigh these risks, marking an improvement over existing treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. Chuk, MK., Chang, JT., Theoret, MR., et al.[2021]

In a study of 88 advanced melanoma patients treated with pembrolizumab, 81.8% experienced any-grade toxicities, with skin and gastrointestinal issues being the most common side effects.

Despite the high incidence of side effects, pembrolizumab was found to be well tolerated in real-world settings, and severe toxicities were manageable with systemic steroids.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world experience with pembrolizumab toxicities in advanced melanoma patients: a single-center experience in the UK. So, AC., Board, RE.[2022]

In a study of 655 patients with advanced melanoma, pembrolizumab showed a 5-year overall survival rate of 34%, with even better outcomes (41%) for treatment-naive patients, indicating its long-term efficacy.

The treatment was generally well-tolerated, with 86% of patients experiencing treatment-related adverse events, but only 7.8% discontinued due to these effects, suggesting a manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Five-year survival outcomes for patients with advanced melanoma treated with pembrolizumab in KEYNOTE-001. Hamid, O., Robert, C., Daud, A., et al.[2023]

Pembrolizumab, a PD-1 inhibitor, has demonstrated clinical effectiveness in treating various solid tumors, particularly in patients with PD-L1-positive non-small-cell lung cancer and unresectable/metastatic melanoma.

Early-phase trials and ongoing studies are focused on further confirming the clinical benefits of pembrolizumab in thoracic malignancies, highlighting its potential as a significant treatment option in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. Karim, S., Leighl, N.[2017]

Pembrolizumab is a monoclonal antibody that effectively blocks the PD-1 receptor on T cells, enhancing their ability to attack cancer cells, particularly in melanoma patients.

In a Phase I study involving 411 patients, pembrolizumab demonstrated high durable response rates with minimal toxicity, indicating its potential as a safe and effective treatment option for melanoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab joins the anti-PD-1 armamentarium in the treatment of melanoma. Hersey, P., Gowrishankar, K.[2017]

Pembrolizumab is a safe and effective immune checkpoint inhibitor that targets the PD-1 receptor, currently approved for treating advanced melanoma and metastatic non-small cell lung cancer (NSCLC).

Ongoing studies are exploring the potential of pembrolizumab in combination with other treatments for lung cancer and other cancer types, while also investigating biomarkers that may predict patient response to this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of PD-L1 positive advanced or metastatic non-small cell lung cancer. Dang, TO., Ogunniyi, A., Barbee, MS., et al.[2020]

References

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

Updated Analysis of KEYNOTE-024: Pembrolizumab Versus Platinum-Based Chemotherapy for Advanced Non-Small-Cell Lung Cancer With PD-L1 Tumor Proportion Score of 50% or Greater. [2022]

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

Long-Term Overall Survival From KEYNOTE-021 Cohort G: Pemetrexed and Carboplatin With or Without Pembrolizumab as First-Line Therapy for Advanced Nonsquamous NSCLC. [2021]

3. Ireland pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. [2022]

4. New Zealand pubmed.ncbi.nlm.nih.gov

Pembrolizumab: first global approval. [2021]

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

89Zr-pembrolizumab Uptake Predicts Survival and Immunotherapy Response. [2022]

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

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. [2021]

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

Real-world experience with pembrolizumab toxicities in advanced melanoma patients: a single-center experience in the UK. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Five-year survival outcomes for patients with advanced melanoma treated with pembrolizumab in KEYNOTE-001. [2023]

9. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. [2017]

10. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab joins the anti-PD-1 armamentarium in the treatment of melanoma. [2017]

11. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of PD-L1 positive advanced or metastatic non-small cell lung cancer. [2020]