Pembrolizumab for Solid Tumors

(INSPIRE Trial)

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University Health Network, Toronto

Must not be taking: Immunosuppressants, Steroids, Monoclonal antibodies

Disqualifiers: Active infection, CNS metastases, Autoimmune disease, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: 5 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests pembrolizumab, a medicine that helps the immune system fight cancer by blocking a protein that usually inhibits it. Researchers aim to observe how gene changes and immune markers respond to this treatment in patients with solid tumors. It suits those diagnosed with advanced cancers, such as certain head and neck cancers, triple-negative breast cancer, ovarian cancer, melanoma, or other advanced solid tumors that cannot be removed or have spread. Participants should have tried standard treatments without success or have no suitable standard options remaining. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important cancer research.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot be on systemic steroid therapy or any other form of immunosuppressive therapy within 7 days before starting the trial treatment. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that pembrolizumab is likely to be safe for humans?

Research has shown that pembrolizumab is generally well-tolerated by patients with various solid tumors. Most individuals can undergo the treatment without major issues. Studies on pembrolizumab in solid cancers indicate that while some may experience side effects, these are usually manageable. Common side effects include fatigue, rash, and itchiness. Serious side effects are less common but can occur.

Previous patients who received pembrolizumab for various cancers have provided valuable safety information. In these cases, pembrolizumab was administered in similar doses and schedules as in this trial. The results demonstrated that the treatment was safe for most patients. Notably, the FDA has already approved pembrolizumab for treating other types of cancer, which supports its safety.

For those considering joining a trial with pembrolizumab, this existing data can offer reassurance about its safety. However, discussing any concerns with a doctor is always important. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Pembrolizumab is unique because it is an immunotherapy that enhances the body's immune system to fight cancer cells. Unlike traditional chemotherapy, which directly targets and kills cancer cells but can also harm healthy cells, pembrolizumab works by blocking the PD-1 pathway. This pathway is often used by cancer cells to hide from the immune system, so by blocking it, pembrolizumab helps the immune system recognize and attack the cancer. Researchers are excited about pembrolizumab because it offers a more targeted approach with the potential for fewer side effects and has shown promise in treating a variety of solid tumors.

What evidence suggests that pembrolizumab might be an effective treatment for solid tumors?

Research has shown that pembrolizumab, the treatment under study in this trial, can help treat solid tumors. In some studies, up to 33% of patients experienced significant tumor shrinkage. Pembrolizumab enhances the immune system's ability to attack cancer cells. Long-term evidence indicates that pembrolizumab can reduce the risk of death by 29% for patients with certain advanced cancers. This treatment has consistently improved survival rates. ^{1 6 7 8 9}

Who Is on the Research Team?

Lillian Siu, M.D.

Principal Investigator

Princess Margaret Cancer Centre

Are You a Good Fit for This Trial?

Adults with advanced solid tumors that are incurable and have failed standard therapy or for whom no standard therapy exists. Participants must be willing to provide tumor tissue samples, use birth control, and have adequate organ function. Excluded are those with prior anti-PD-1/L1/L2 treatment, active infections including HIV/Hepatitis B/C, CNS metastases, certain malignancies or conditions that could affect trial participation.

Inclusion Criteria

Be willing and able to provide written informed consent/assent for the trial

My cancer is advanced, cannot be cured, and has not responded to or is not suitable for standard treatments.

I am willing and able to provide a new tissue sample from my tumor for the study.

Exclusion Criteria

Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the patient's participation for the full duration of the trial, or is not in the best interest of the patient to participate, in the opinion of the treating investigator

I have an immune system disorder or have been on steroids or other immune-weakening medicines in the last week.

I have a history of active tuberculosis.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive pembrolizumab by intravenous infusion every 3 weeks

5 years

Visits every 3 weeks for infusion

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Pembrolizumab

Trial Overview The study is testing Pembrolizumab's effectiveness on various solid tumors by blocking a protein called PD-L1 to enhance the immune system's ability to destroy cancer cells. It aims to evaluate gene changes and immune biomarkers in relation to the treatment response.

How Is the Trial Designed?

Group I: Pembrolizumab Experimental Treatment 1 Intervention

Pembrolizumab will be given by intravenous infusion (IV, given by vein) at a dose of 200 mg, once every 3 weeks.

Pembrolizumab is already approved in United States, European Union, United Kingdom for the following indications:

Approved in United States as KEYTRUDA for:

• Head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
• Melanoma
• Non-small cell lung cancer (NSCLC)
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Hepatocellular carcinoma
• Renal cell carcinoma
• Cervical cancer
• Endometrial carcinoma

Approved in European Union as KEYTRUDA for:

• Head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
• Melanoma
• Non-small cell lung cancer (NSCLC)
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Hepatocellular carcinoma
• Renal cell carcinoma
• Cervical cancer
• Endometrial carcinoma

Approved in United Kingdom as KEYTRUDA for:

• Untreated metastatic or unresectable recurrent head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1

Who Is Running the Clinical Trial?

University Health Network, Toronto

Lead Sponsor

Trials

1,555

Recruited

526,000+

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

Published Research Related to This Trial

Pembrolizumab, a PD-1 inhibitor used in cancer treatment, can lead to rare but serious immune-related adverse events, including type 1 diabetes mellitus, occurring in about 0.2% of cases.

A review of 42 cases revealed that patients may develop diabetic ketoacidosis during treatment, highlighting the need for blood glucose monitoring and awareness of this potential side effect among clinicians.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Programmed Cell Death-1 Inhibitor-Induced Type 1 Diabetes Mellitus. Clotman, K., Janssens, K., Specenier, P., et al.[2022]

Pembrolizumab, an immune checkpoint inhibitor, can cause pneumonitis in 1%-5% of patients, and this case report highlights an atypical presentation of this side effect in a patient with metastatic squamous cell carcinoma.

The patient was successfully treated with steroid therapy after ruling out other potential causes, leading to complete resolution of the pneumonitis, emphasizing the importance of recognizing and managing atypical cases of checkpoint inhibitor-pneumonitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. Jeon, WJ., Nguyen, J., Castillo, DR., et al.[2023]

Pembrolizumab (Keytruda) was approved by the FDA for treating metastatic non-small cell lung cancer (mNSCLC) in patients with tumors expressing PD-L1, showing significant improvements in overall survival (OS) and progression-free survival (PFS) in two major clinical trials with thousands of participants.

In the KEYNOTE-024 trial, pembrolizumab demonstrated a 40% reduction in the risk of death compared to chemotherapy, while in the KEYNOTE-010 trial, it also showed a significant survival advantage over chemotherapy in patients who had previously progressed on treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for Treatment of Metastatic Non-Small Cell Lung Cancer: First-Line Therapy and Beyond. Pai-Scherf, L., Blumenthal, GM., Li, H., et al.[2022]

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 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]

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) 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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11229185/

Tumor dynamics in patients with solid tumors treated with ... Results of other studies have shown that up to 33% of patients TBP exhibit a reduction in target tumor burden of ≥30%, with many more patients ...

2. merck.com merck.com/news/ten-year-data-for-mercks-keytruda-pembrolizumab-demonstrates-sustained-overall-survival-benefit-versus-ipilimumab-in-advanced-melanoma/

Ten-Year Data for Merck's KEYTRUDA® (pembrolizumab ... KEYTRUDA demonstrated a sustained OS benefit, reducing the risk of death by 29% (HR=0.71 [95% CI, 0.60-0.85]). At 10 years, KEYTRUDA more than ...

3. keytrudahcp.com keytrudahcp.com/efficacy/

Efficacy Data for KEYTRUDA® (pembrolizumab) The most common adverse reactions (≥20%) were decreased appetite (25%), fatigue (25%), dyspnea (23%), and nausea (20%). In KEYNOTE⁠-⁠671, adverse reactions ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38451314/

Clinical evidence for efficacy of pembrolizumab in MSI-H ... Our retrospective study evaluated the clinical efficacy and safety of pembrolizumab in treating advanced solid tumors with either MSI-H or TMB-H.

5. clinicaltrials.gov clinicaltrials.gov/study/NCT01295827

NCT01295827 | Study of Pembrolizumab (MK-3475) in ... The study will investigate the safety, tolerability, and efficacy of pembrolizumab (2 mg/kg and 10 mg/kg) in participants with advanced or metastatic MEL.

6. merck.com merck.com/product/usa/pi_circulars/k/keytruda/keytruda_pi.pdf

keytruda_pi.pdf Safety data are available for the first 203 patients who received KEYTRUDA and ... or MSI-H solid tumors received KEYTRUDA 2 mg/kg every 3 weeks. The median ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5628692/

Safety and efficacy profile of pembrolizumab in solid cancer The aim of the present review is to systematically evaluate the efficacy and safety of pembrolizumab by analyzing survival outcomes and at ...

8. keytrudahcp.com keytrudahcp.com/safety/adverse-reactions/

Select Adverse Reactions for KEYTRUDA® (pembrolizumab) The safety and effectiveness of KEYTRUDA as a single agent have been established in pediatric patients with melanoma, MCC, and MSI⁠-⁠H or dMMR cancer. Use of ...

9. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/25977344/

Phase I Study of Pembrolizumab (MK-3475; Anti-PD-1 ... Conclusions: Pembrolizumab was well tolerated and associated with durable antitumor activity in multiple solid tumors. The lowest dose with full ...