Neoadjuvant PD-1 Blockade for Melanoma

Not currently recruiting at 2 trial locations

Overseen By Giorgos Karakousis, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Abramson Cancer Center of the University of Pennsylvania

Must not be taking: Immunosuppressants, Steroids, Live vaccines, others

Disqualifiers: Unresectable disease, Autoimmune disease, others

Stay on Your Current Meds You can continue your current medications while participating

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

Compensation: Varies

Number of Visits: 19

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if pembrolizumab (also known as KEYTRUDA, a PD-1 blocking drug) administered before surgery can reduce the spread of melanoma to nearby lymph nodes in patients with Stage IIB or IIC melanoma. Patients receive pembrolizumab once before surgery and continue treatment for up to a year post-surgery. The trial suits individuals with Stage IIB or IIC melanoma who have not previously received similar drugs and can undergo surgical removal of their melanoma. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you are on immunosuppressive therapy or certain other treatments, you may need to stop them before starting the trial. It's best to discuss your specific medications with the trial team.

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

Research shows that pembrolizumab is generally safe for people with melanoma. Several studies have found it to be well-tolerated. For those with stage III or IV melanoma, pembrolizumab did not cause unexpected side effects or delay surgery. One study found that a single dose of pembrolizumab did not delay surgery and was safe for patients whose melanoma could be surgically removed.

These findings suggest that pembrolizumab is a reliable treatment option for melanoma, especially before surgery. Patients should discuss any concerns with their doctor to determine if this treatment is suitable. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for melanoma?

Researchers are excited about pembrolizumab for melanoma because it offers a unique approach compared to traditional treatments like surgery, chemotherapy, or radiation. Pembrolizumab is an immunotherapy that works by blocking the PD-1 pathway, which can help the immune system recognize and attack cancer cells more effectively. This mechanism of action is different from conventional therapies that directly target cancer cells, offering the potential for a more targeted and possibly longer-lasting response. Additionally, starting pembrolizumab before surgery (neoadjuvant) may shrink tumors and make surgical removal more effective and less invasive. This approach could also reduce the risk of cancer recurrence by addressing microscopic disease early on.

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

Research has shown that pembrolizumab, a medicine that blocks PD-1, yields promising results in treating melanoma, a type of skin cancer. In earlier studies with patients who had stage III and IV melanoma, pembrolizumab extended their survival. Specifically, data from 10 years of research revealed that more than one-third of patients with advanced melanoma remained alive after treatment. This suggests that pembrolizumab can help the immune system fight cancer cells. In this trial, participants will receive neoadjuvant pembrolizumab before undergoing wide excision and sentinel lymph node biopsy. Although previous results are from patients with more advanced stages, they strongly suggest that pembrolizumab could also be effective for stage II melanoma. ^{1 2 6 7 8}

Who Is on the Research Team?

Giorgos Karakousis, MD

Principal Investigator

Abramson Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults over 18 with Stage IIB/C melanoma that can be surgically removed. They must have good performance status, normal organ function, and agree to contraception rules. Excluded are those with non-resectable melanoma, recent treatments or surgeries, severe allergies to pembrolizumab, active infections including HIV/Hepatitis B/C/TB, certain heart diseases, live vaccines taken recently, immunodeficiencies or suppressive therapies within a week before the trial.

Inclusion Criteria

My melanoma is at stage IIB or IIC and can be surgically removed. I do not have uveal or mucosal melanoma.

I am not pregnant and follow the required birth control guidelines.

I agree to follow the study's rules for using birth control.

Exclusion Criteria

I have not received a live vaccine in the last 30 days.

My liver is not functioning well (Child-Pugh score >6).

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

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Treatment

Participants receive one dose of pembrolizumab 200 mg

3 weeks

1 visit (in-person)

Surgery

Participants undergo wide excision and sentinel lymph node biopsy

1 day

1 visit (in-person)

Adjuvant Treatment

Participants receive up to 1 year of adjuvant pembrolizumab 200 mg every 3 weeks

1 year

Approximately 17 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Approximately 5 years

What Are the Treatments Tested in This Trial?

Interventions

• Pembrolizumab
• Wide Excision and Sentinel Lymph Node (SLN) Biopsy

Trial Overview The study tests if pembrolizumab given before surgery reduces positive sentinel lymph nodes in patients with Stage IIB/C melanoma. Participants receive one dose of pembrolizumab followed by surgery after about three weeks and then up to one year of adjuvant therapy post-operation.

How Is the Trial Designed?

Group I: Neoadjuvant Pembrolizumab Experimental Treatment 2 Interventions

Subjects will receive one dose of pembrolizumab 200 mg. Approximately 3 weeks after the initial dose of pembrolizumab, subjects will undergo wide excision and sentinel lymph node (SLN) biopsy. Post-operatively, subjects will receive up to 1 year of adjuvant pembrolizumab 200 mg every 3 weeks.

Who Is Running the Clinical Trial?

Abramson Cancer Center of the University of Pennsylvania

Lead Sponsor

Trials

360

Recruited

108,000+

Abramson Cancer Center at Penn Medicine

Lead Sponsor

Trials

425

Recruited

464,000+

Published Research Related to This Trial

In a phase 2 study of 23 patients with high-risk resectable melanoma, the combination of ipilimumab and nivolumab showed high response rates (73% overall response rate and 45% pathologic complete response) but also resulted in significant toxicity, with 73% of patients experiencing grade 3 treatment-related adverse events.

Nivolumab monotherapy had lower response rates (25% overall response rate and 25% pathologic complete response) but was associated with much lower toxicity (only 8% grade 3 treatment-related adverse events), suggesting that while combination therapy is effective, it comes with higher risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant immune checkpoint blockade in high-risk resectable melanoma. Amaria, RN., Reddy, SM., Tawbi, HA., 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]

In a study of 66 patients with advanced melanoma treated with PD-1 antibodies, those with elevated baseline serum lactate dehydrogenase (LDH) had significantly shorter overall survival compared to those with normal LDH levels, indicating that LDH can be a critical prognostic marker.

Changes in LDH levels during treatment were predictive of response; patients with a reduction in LDH were more likely to achieve partial remission, while those with an increase had a shorter overall survival, suggesting LDH could help monitor treatment effectiveness early on.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Serum lactate dehydrogenase as an early marker for outcome in patients treated with anti-PD-1 therapy in metastatic melanoma. Diem, S., Kasenda, B., Spain, L., et al.[2022]

In a study of 37 patients with stage IV metastatic melanoma, high levels of soluble CD73 (sCD73) enzyme activity in the serum were linked to significantly poorer overall survival and progression-free survival when treated with nivolumab.

Patients with high sCD73 activity had a median progression-free survival of only 2.6 months compared to 14.2 months for those with lower activity, suggesting that measuring sCD73 could help predict how well patients will respond to nivolumab therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Soluble CD73 as biomarker in patients with metastatic melanoma patients treated with nivolumab. Morello, S., Capone, M., Sorrentino, C., et al.[2018]

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 an overall objective response rate of 33%, indicating its efficacy in treating this type of cancer.

The median overall survival for patients receiving pembrolizumab was 23 months, with a 12-month survival rate of 66%, while 14% of patients experienced severe treatment-related adverse events, highlighting its safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association of Pembrolizumab With Tumor Response and Survival Among Patients With Advanced Melanoma. Ribas, A., Hamid, O., Daud, A., et al.[2022]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37414215/

Long-term outcomes to neoadjuvant pembrolizumab based on ... The goal of this study was to determine long-term outcomes for stage III/IV melanoma patients treated with neoadjuvant and adjuvant programmed cell death ...

2. nejm.org nejm.org/doi/full/10.1056/NEJMoa2211437

Neoadjuvant–Adjuvant or Adjuvant-Only Pembrolizumab in ... Therefore, it has been hypothesized that neoadjuvant therapy may be able to activate more antitumor T cells and improve clinical outcomes than ...

3. 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 ...

4. annalsofoncology.org annalsofoncology.org/article/S0923-7534(23)00734-2/fulltext

Long-term outcomes to neoadjuvant pembrolizumab based ... The 5-year data from this trial represent the longest follow-up of a single-agent neoadjuvant PD-1 trial to date, and these results both confirm ...

5. keytrudahcp.com keytrudahcp.com/efficacy/

Efficacy Data for KEYTRUDA® (pembrolizumab) Health care professionals may review efficacy data for KEYTRUDA® (pembrolizumab), browse the indications and select the corresponding KEYNOTE trials for ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11232562/

Long-term outcomes to neoadjuvant pembrolizumab based ... The goal of this study was to determine long-term outcomes for stage III/IV melanoma patients treated with neoadjuvant and adjuvant programmed cell death ...

7. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.9502

Neoadjuvant-adjuvant pembrolizumab in clinical stage IIB/ ... Neoadjuvant therapy in clinical stage IIB/C was safe and feasible, with no significant delay in surgery or new or unexpected toxicities noted in these patients.

8. onclive.com onclive.com/view/neoadjuvant-pembrolizumab-is-safe-and-effective-in-resectable-stage-iii-iv-melanoma

Neoadjuvant Pembrolizumab Is Safe and Effective in ... Single-dose neoadjuvant pembrolizumab was safe with no surgical delays and boosted MPR rates in resectable melanoma.