Pembrolizumab + CMP-001 for Melanoma

Not currently recruiting at 215 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: Immunosuppressants, Steroids

Disqualifiers: Mucosal melanoma, Uveal melanoma, 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: 7

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate the effectiveness of pembrolizumab, alone or with CMP-001, in treating surgically removable melanoma. Pembrolizumab is an immunotherapy drug that helps the immune system attack cancer, while CMP-001 may enhance this effect. The research tests whether adding CMP-001 improves pembrolizumab's ability to shrink tumors and prevent recurrence. Individuals with surgically removable melanoma who have not received certain cancer treatments before might be suitable candidates. 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 does not specify if you need to stop taking your current medications. However, you cannot be on certain immunosuppressive therapies or high-dose steroids, and you must not have received prior systemic therapy for melanoma.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that pembrolizumab, a treatment for melanoma, has been studied for its safety and effectiveness. Some patients experience side effects, with serious ones, known as Grade 3 to 5 adverse events, occurring in about half of the patients. These serious side effects led to treatment discontinuation in about 13% of cases, and unfortunately, about 6% of patients died as a result. However, pembrolizumab is already approved for treating other conditions, suggesting it is generally well-tolerated.

For the combination of CMP-001 and pembrolizumab, studies suggest that side effects are usually manageable. While side effects can occur, they typically do not require stopping the treatment. CMP-001 alone was also well-tolerated. This is promising for those considering joining a trial, as the combination treatment appears safe for most patients. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they combine pembrolizumab, a well-known immunotherapy drug, with CMP-001, an innovative immune modulator. Unlike standard treatments that mainly rely on surgery or chemotherapy, pembrolizumab works by blocking the PD-1 pathway to boost the immune system's ability to fight melanoma. CMP-001 adds a unique twist by activating the immune system directly within the tumor, potentially enhancing pembrolizumab's effects. This combination aims to offer a more potent and targeted defense against melanoma, providing hope for improved outcomes.

What evidence suggests that this trial's treatments could be effective for melanoma?

Studies have shown that pembrolizumab, which participants in this trial may receive, effectively treats advanced melanoma, with more than one-third of patients living at least ten years after treatment. In 43% of patients treated with pembrolizumab, the cancer did not progress, and many experienced tumor shrinkage. In this trial, some participants will receive pembrolizumab alone, while others will receive a combination of CMP-001 and pembrolizumab. Research suggests that combining CMP-001 with pembrolizumab shows early promise for patients whose melanoma does not respond to traditional treatments. This combination has led to noticeable and lasting tumor responses, with tumors either shrinking or stopping growth for a long time without causing major side effects. These findings suggest that using pembrolizumab alone or with CMP-001 could effectively treat melanoma. ^{1 3 6 7 8}

Who Is on the Research Team?

Ahmad Tarhini

Principal Investigator

ECOG-ACRIN Cancer Research Group

Are You a Good Fit for This Trial?

Adults with operable melanoma, specifically nodal or in-transit cutaneous metastases, and no prior melanoma treatment can join. They must have good performance status (ECOG 0 or 1), injectable/measurable disease by scans, normal organ function tests, not be pregnant/breastfeeding, and willing to sign consent. Excluded are those with adrenal insufficiency, mucosal/uveal melanoma, brain metastases, severe heart/cardiac issues, immunodeficiency or on immunosuppressants.

Inclusion Criteria

I can understand and am willing to sign the consent form.

Your liver enzymes (AST and ALT) are not more than 2.5 times the normal limit.

My kidney function, measured by creatinine levels, is within the normal range.

Exclusion Criteria

Patients with adrenal insufficiency are ineligible

I have not had any systemic therapy for melanoma.

I have never needed steroids for non-infectious lung inflammation.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Phase

Patients receive pembrolizumab alone or in combination with CMP-001 for up to 3 cycles

9 weeks

3 visits (in-person) per cycle

Surgery

Patients undergo surgery 1-2 weeks after completion of neoadjuvant phase

1-2 weeks

Adjuvant Phase

After recovery from surgery, patients receive pembrolizumab for up to 16 cycles

48 weeks

1 visit (in-person) every 6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 15 years

Every 3 months if < 2 years from study entry, every 6 months if 2-5 years, every 12 months if > 5 years

What Are the Treatments Tested in This Trial?

Interventions

• CMP-001
• Pembrolizumab

Trial Overview The trial is testing if pembrolizumab alone or combined with CMP-001 improves outcomes for patients with surgically treatable melanoma. Pembrolizumab is an antibody that may help the immune system fight cancer; CMP-001 might boost this effect.

How Is the Trial Designed?

Group I: Arm B (CMP-001, pembrolizumab) Experimental Treatment 7 Interventions

NEOADJUVANT PHASE: Patients receive CMP-001 SC on day 1 of cycle 1 and then intratumorally on days 8 and 15 of cycle 1, days 1, 8, and 15 of cycle 2, and day 1 of cycle 3. Patients also receive pembrolizumab IV over 30 minutes on day 8 of each cycle. Treatment repeats every 21 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity. SURGERY: Patients undergo surgery 1-2 weeks after completion of neoadjuvant phase. ADJUVANT PHASE: After recovery from surgery, patients receive pembrolizumab IV over 30 minutes on day 1 of every other cycle. Treatment repeats every 21 days for up to 16 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or PET/CT throughout the trial and may undergo optional biopsy at baseline and disease progression and optional collection of blood samples throughout the trial.

Group II: Arm A (pembrolizumab) Experimental Treatment 6 Interventions

NEOADJUVANT PHASE: Patients receive pembrolizumab IV over 30 minutes on day 1 of each cycle. Treatment repeats every 21 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity. SURGERY: Patients undergo surgery 1-2 weeks after completion of neoadjuvant phase. ADJUVANT PHASE: After recovery from surgery, patients receive pembrolizumab IV over 30 minutes on day 1 of every other cycle. Treatment repeats every 21 days for up to 16 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or PET/CT throughout the trial and may undergo optional biopsy at baseline and disease progression and optional collection of blood samples throughout the trial.

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?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

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]

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) effectively blocks the PD-1 pathway, enhancing T-cell activity against tumors, which supports its role in promoting tumor regression and immune rejection.

Preclinical studies in cynomolgus monkeys showed that pembrolizumab has a favorable safety profile with no significant toxicological findings, aligning with its demonstrated safety and efficacy in human clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biophysical and Immunological Characterization and In Vivo Pharmacokinetics and Toxicology in Nonhuman Primates of the Anti-PD-1 Antibody Pembrolizumab. Hutchins, B., Starling, GC., McCoy, MA., et al.[2021]

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]

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]

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]

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]

In a randomized trial comparing FDA-approved immune checkpoint inhibitors for advanced melanoma, pembrolizumab showed significantly better treatment outcomes than ipilimumab.

This study is notable as it is the first to directly compare these two therapies as first-line treatments, highlighting pembrolizumab's potential as a more effective option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab superior to ipilimumab in melanoma. [2017]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT02680184

NCT02680184 | Clinical Study of CMP-001 in Combination ... The primary objective of the Treatment Extension is to assess the safety profile of CMP-001 when given in combination with pembrolizumab or as monotherapy in ...

2. ecancer.org ecancer.org/en/news/13768-aacr-2018-tlr9-agonist-cmp-001-pembrolizumab-combination-shows-early-efficacy-in-patients-with-metastatic-melanoma-resistant-to-anti-pd-1

AACR 2018: TLR9 agonist CMP-001 / pembrolizumab ... AACR 2018: TLR9 agonist CMP-001 / pembrolizumab combination shows early efficacy in patients with metastatic melanoma resistant to anti-PD-1.

3. immuno-oncologynews.com immuno-oncologynews.com/2018/05/04/advanced-melanoma-patients-responding-to-cmp-001-keytruda-combo-immunotherapy-phase-1-study-reports/

Advanced Melanoma Patients Seen to Respond to CMP ... Overall, these results show that combining CMP-001 with Keytruda resulted in objective, durable tumor responses without triggering major ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12318270/

Intratumoral vidutolimod as monotherapy or in combination ... Median duration of response was 25.2 months with vidutolimod PS20‐A plus pembrolizumab, 11.4 months with vidutolimod PS20‐B plus pembrolizumab, ...

5. medicine.uiowa.edu medicine.uiowa.edu/news/2018/04/new-immunotherapy-combination-shows-promise-melanoma-treatment

New immunotherapy combination shows promise for ... The study shows the combination was well tolerated in patients and suggests it could be effective against advanced melanoma that has either not ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT03084640

NCT03084640 | Phase 1B Study Evaluating Alternative ... Participants will continue treatment with CMP-001 in combination with pembrolizumab as long as they do not experience unacceptable toxicities and when continued ...

7. onclive.com onclive.com/view/cmp-001-plus-pembrolizumab-elicits-deep-responses-reverses-pd-1-resistance-in-advanced-melanoma

CMP-001 Plus Pembrolizumab Elicits Deep Responses ... Results showed that CMP-001 plus pembrolizumab led to a best overall response rate (ORR) per RECIST v1.1 criteria of 23.5% (95% CI, 15.5-33.1), ...

8. jitc.bmj.com jitc.bmj.com/content/8/Suppl_3/A186

304 Intratumoral injection of CMP-001, a toll-like receptor 9 ... Conclusions Intratumoral CMP-001 was well-tolerated and provided both local and distant responses in patients with advanced melanoma with ...