Pembrolizumab for Advanced Cancers

Overseen By Aung Naing

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Immunosuppressants, Steroids

Disqualifiers: Active infection, Autoimmune disease, CNS metastases, 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: 22

Duration: 24 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests pembrolizumab, a medication that may help the immune system combat rare cancers that can't be surgically removed or have spread. Pembrolizumab, a type of monoclonal antibody, targets specific proteins to potentially slow tumor growth. The trial evaluates the effectiveness of this treatment in patients who have tried other unsuccessful therapies. It suits those with specific advanced tumors, such as squamous cell skin cancer or small cell tumors from non-lung areas, whose cancer has progressed after standard treatments. Participants must have tumors that can be measured or biopsied.

As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

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 participate if you are currently receiving other cancer treatments like chemotherapy or immunotherapy. Hormone replacement therapy and stable hormonal therapy for certain cancers are allowed.

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

Research has shown that pembrolizumab is generally safe, and its side effects can be managed. A large review of 31 clinical trials found that this treatment is usually well-tolerated across various health conditions. These studies, which included thousands of patients, support this conclusion. Some individuals might experience side effects while using pembrolizumab, but these are typically manageable. Monitoring any reactions and consulting the medical team if concerns arise is important. Overall, pembrolizumab is considered safe for many patients. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Pembrolizumab is unique because it works by harnessing the power of the immune system to fight cancer. Unlike traditional chemotherapy, which directly attacks cancer cells but can also harm healthy cells, pembrolizumab is an immune checkpoint inhibitor. It specifically targets and blocks the PD-1 pathway, allowing the immune system to better recognize and attack cancer cells. Researchers are excited about pembrolizumab because it has the potential to provide a more targeted treatment with fewer side effects, offering new hope for patients with advanced cancers.

What evidence suggests that pembrolizumab might be an effective treatment for advanced cancers?

Research has shown that pembrolizumab, the treatment under study in this trial, can help treat advanced cancers. In one study with patients who had advanced melanoma, over one-third remained alive 10 years after starting treatment with pembrolizumab. Another study found that 84.3% of patients who completed all treatment cycles responded well to pembrolizumab. This medication targets certain proteins on white blood cells, boosting the immune system to help control tumor growth. These findings suggest that pembrolizumab could be a promising option for managing some advanced cancers. ^{6 7 8 9 10}

Who Is on the Research Team?

Aung Naing, MD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for patients with rare, inoperable or metastatic tumors who've had previous treatments fail within 6 months. They must have measurable disease, be willing to use birth control and provide tissue samples. Excluded are those with active hepatitis B/C, CNS metastases (for certain cohorts), other cancer treatments ongoing, immunodeficiency issues, known pneumonitis or TB history.

Inclusion Criteria

I am not pregnant and agree to use birth control.

I agree to use birth control.

My cancer can be measured by scans or has visible changes on scans.

Exclusion Criteria

I have a history of or currently have non-infectious lung inflammation.

I am currently being treated for an infection.

I have been treated for an autoimmune disease in the last 2 years.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive pembrolizumab intravenously over 30 minutes on day 1, with treatment repeating every 21 days for up to 24 months

24 months

Every 21 days

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

30 days and then every 12 weeks

1 visit at 30 days, then every 12 weeks

Extension

Participants with clinical response or disease stabilization may continue treatment for up to an additional 12 months

12 months

What Are the Treatments Tested in This Trial?

Interventions

• Pembrolizumab

Trial Overview The study tests pembrolizumab's effectiveness on various advanced solid tumors that can't be surgically removed or have spread. Pembrolizumab is a monoclonal antibody designed to block proteins on white blood cells to potentially boost the immune system against tumor growth.

How Is the Trial Designed?

Group I: Treatment (pembrolizumab) Experimental Treatment 3 Interventions

Patients receive pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 24 months in the absence of disease progression or toxicity. Patients with clinical response or disease stabilization may continue treatment for up to an additional 12 months.

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?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

In a study of 24 patients with advanced non-small cell lung cancer (NSCLC) treated with pembrolizumab, the objective response rate was 45.8%, indicating that nearly half of the patients experienced a reduction in tumor size after treatment.

Pembrolizumab showed promising results even in PD-L1-negative patients, with a major pathological response of 75% and a pathological complete response of 50% in those who underwent surgery, suggesting its potential effectiveness across different patient profiles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of pembrolizumab for the treatment of advanced non-small cell lung cancer: a retrospective, single-centre, single-arm study. Guo, T., Ding, Y., Chen, L., et al.[2022]

Pembrolizumab was found to be safe and well tolerated in a phase I study involving 20 patients with advanced solid tumors, with no dose-limiting toxicities observed at doses up to 10 mg/kg every 2 weeks.

The treatment demonstrated durable antitumor activity, with complete responses in two patients and stable disease in 15 others, indicating that a minimum effective dose for antitumor activity is 2 mg/kg every 3 weeks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I Study of Pembrolizumab (MK-3475; Anti-PD-1 Monoclonal Antibody) in Patients with Advanced Solid Tumors. Patnaik, A., Kang, SP., Rasco, D., 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, 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 (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 (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 (Keytruda) is an effective treatment for advanced melanoma, showing significant improvements in progression-free survival and overall response rates compared to ipilimumab and chemotherapy in clinical trials involving patients with varying treatment histories.

The drug has a manageable safety profile, with immune-related side effects that are generally reversible, making it a valuable option for patients who have not responded to other therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab: A Review in Advanced Melanoma. Deeks, ED.[2022]

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, 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]

Citations

1. 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 ... At 10 years, more than one-third (34.0%) of patients with advanced melanoma were alive after treatment with KEYTRUDA, compared to 23.6% of patients treated ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10082298/

Five-Year Outcomes With Pembrolizumab Versus ... Objective response rate was 84.3% among 102 patients who completed 35 cycles of pembrolizumab and 15.2% among 33 patients who received second-course ...

3. 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.

4. keytrudahcp.com keytrudahcp.com/efficacy/

Efficacy Data for KEYTRUDA® (pembrolizumab) The most common adverse reactions (≥20%) with KEYTRUDA were nausea (56%), fatigue (56%), constipation (35%), diarrhea (31%), decreased appetite (28%), rash (25 ...

5. ascopubs.org ascopubs.org/doi/10.1200/JCO.21.02885

Five-Year Outcomes With Pembrolizumab Versus ... With 5-year OS rates of up to 22%, these data support the continued use of pembrolizumab monotherapy as a standard-of-care treatment for ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11227881/

Safety profile of pembrolizumab monotherapy based on an ... Pembrolizumab has a manageable safety profile as described in its label, which was primarily based on 2799 patients who participated in clinical trials for ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38295556/

Safety profile of pembrolizumab monotherapy based on an ... This pooled analysis of 31 clinical trials showed that pembrolizumab has a consistent safety profile across indications.

8. merck.com merck.com/news/merck-announces-keytruda-pembrolizumab-plus-welireg-belzutifan-met-primary-endpoint-of-disease-free-survival-dfs-in-certain-patients-with-clear-cell-renal-cell-carcinoma-rcc-follow/

Merck Announces KEYTRUDA® (pembrolizumab) Plus ... The safety profiles of KEYTRUDA plus WELIREG in this trial were overall consistent with those observed in previously reported studies for ...

9. sciencedirect.com sciencedirect.com/science/article/pii/S0959804924008025

Safety of pembrolizumab as adjuvant therapy in a pooled ... Clinical trial and surveillance data have demonstrated that pembrolizumab has a manageable and consistent safety profile in patients with advanced or metastatic ...

10. aacrjournals.org aacrjournals.org/clincancerres/article/21/19/4286/125563/Phase-I-Study-of-Pembrolizumab-MK-3475-Anti-PD-1

Phase I Study of Pembrolizumab (MK-3475; Anti–PD-1 ... PD-1 and PD-L1 inhibition have also shown acceptable safety and tolerability and promising antitumor activity in patients with advanced solid tumors (12–20).