Pembrolizumab + Lenvatinib for Neuroendocrine Prostate Cancer

(PLANE-PC Trial)

Not currently recruiting at 4 trial locations

Overseen By Brittany Brugh

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: University of Michigan Rogel Cancer Center

Must not be taking: Anti-androgens, Immunosuppressants

Disqualifiers: Uncontrolled hypertension, 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

Compensation: Varies

Number of Visits: 1

Duration: Up to 735 days (35 cycles of 21 days each)

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment combination to manage neuroendocrine prostate cancer. It combines two drugs, lenvatinib (a targeted therapy) and pembrolizumab (an immunotherapy), to determine if they can better control cancer growth together. The trial seeks men with prostate cancer that has spread, particularly those with specific cancer characteristics such as high levels of certain markers or genetic changes. This trial may suit individuals whose prostate cancer has spread and exhibits features like a specific protein level or genetic profile. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications, such as anti-androgen medications, before starting the study. However, LHRH agonists and GNRH antagonists can be continued. It's best to discuss your specific medications with the trial team to see if any need to be stopped.

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

Research has shown that the combination of pembrolizumab and lenvatinib has been tested in patients before. In one study, 92% of participants experienced treatment-related side effects, indicating that most people noticed some effects. While side effects are common, they can vary in intensity and type.

Another study examined this combination for different types of neuroendocrine tumors, similar to those targeted in this trial. This suggests ongoing interest in understanding the efficacy of these drugs together.

Since this clinical trial is in Phase 2, some safety information is available, but it is not complete. Phase 2 trials typically assess the treatment's effectiveness and monitor side effects. Prospective participants should discuss potential side effects with the trial team. ^{1 2 3 4 5}

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

Unlike the standard chemotherapy or hormone therapy used for neuroendocrine prostate cancer, the combination of Pembrolizumab and Lenvatinib offers a fresh approach. Pembrolizumab is an immunotherapy that helps the immune system recognize and attack cancer cells, which is different from traditional treatments that directly target the cancer. Lenvatinib, on the other hand, inhibits the growth of blood vessels that feed tumors, potentially starving them of nutrients. Researchers are excited because this dual approach could effectively shrink tumors and improve outcomes by both enhancing immune response and cutting off the tumor's blood supply.

What evidence suggests that this treatment might be an effective treatment for neuroendocrine prostate cancer?

Research has shown that using pembrolizumab and lenvatinib together may help treat certain cancers. In one study, patients lived for about 8 months without their cancer worsening. Another study found that patients lived for about 9.4 months in total. However, most patients experienced side effects from the treatment. This trial will evaluate the combination of pembrolizumab and lenvatinib specifically for neuroendocrine prostate cancer. While these results are promising, more research is needed to confirm the effectiveness of this treatment for this specific type of cancer. ^{1 3 6 7 8}

Who Is on the Research Team?

Ulka Vaishampayan, MD

Principal Investigator

University of Michigan

Are You a Good Fit for This Trial?

Adults (18+) with advanced/metastatic prostate cancer showing neuroendocrine characteristics, not previously treated with certain therapies like VEGF-TKI or immune checkpoint inhibitors. Participants must have an ECOG performance status of 0 or 1, adequate organ function, and agree to use contraception. Exclusions include active CNS metastases, recent live vaccines, severe cardiovascular issues, uncontrolled infections, other active cancers within the past 3 years.

Inclusion Criteria

- Serum chromogranin A level ≥ 5× upper limit of normal (ULN) and/or serum neuron specific enolase (NSE) ≥ 2× ULN.

I agree to use contraception and not donate sperm for 120 days after my last treatment dose.

My cancer is a type that is hard to identify or has changed its characteristics.

Exclusion Criteria

I haven't had cancer treatment or major surgery in the last 3 weeks and have recovered from side effects.

I have or had severe lung inflammation that needed steroids.

I do not have an active, uncontrolled infection.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive lenvatinib and pembrolizumab in 21-day cycles, continuing until progression, toxicity, or decision to discontinue, with a maximum of 35 cycles

Up to 735 days (35 cycles of 21 days each)

1 visit per cycle (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

What Are the Treatments Tested in This Trial?

Interventions

• Lenvatinib
• Pembrolizumab

Trial Overview The trial tests a combination of Pembrolizumab and Lenvatinib for patients with specific types of prostate cancer. Treatment cycles last 21 days and may continue up to a maximum of 35 cycles unless there's disease progression or unacceptable side effects.

How Is the Trial Designed?

Group I: Study Treatment Arm Experimental Treatment 2 Interventions

Lenvatinib 20 mg Orally Day1-21 with Pembrolizumab 200 mg Intravenously (IV) over 30 minutes Day 1. Each cycle = 21 days

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

Approved in United States as Lenvima for:

• Differentiated Thyroid Cancer
• Renal Cell Carcinoma
• Hepatocellular Carcinoma
• Endometrial Cancer

Approved in European Union as Lenvima for:

• Thyroid Cancer
• Renal Cell Carcinoma
• Hepatocellular Carcinoma
• Endometrial Cancer

Approved in European Union as Kisplyx for:

• Renal Cell Carcinoma

Who Is Running the Clinical Trial?

University of Michigan Rogel Cancer Center

Lead Sponsor

Trials

303

Recruited

20,700+

Ulka Vaishampayan

Lead Sponsor

Trials

1

Recruited

50+

Hoosier Cancer Research Network

Collaborator

Trials

69

Recruited

3,800+

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

University of Michigan

Collaborator

Trials

1,891

Recruited

6,458,000+

Published Research Related to This Trial

In the CLEAR study involving 352 patients, the combination of lenvatinib and pembrolizumab showed a manageable safety profile, with common adverse reactions including fatigue (63.1%), diarrhea (61.9%), and hypertension (56.3%).

Most adverse reactions occurred within approximately 5 months of starting treatment, and effective management strategies such as monitoring and dose modifications were identified to ensure patient safety and support ongoing treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characterization and Management of Adverse Reactions From the CLEAR Study in Advanced Renal Cell Carcinoma Treated With Lenvatinib Plus Pembrolizumab. Motzer, R., George, S., Merchan, JR., et al.[2023]

In a phase 3 study involving 487 patients with advanced urothelial carcinoma, the combination of pembrolizumab and lenvatinib did not show improved progression-free survival (4.5 months) or overall survival (11.8 months) compared to pembrolizumab with placebo.

The combination treatment resulted in a higher rate of severe adverse events (51%) compared to the placebo group (27%), leading to the conclusion that the benefit-to-risk ratio was not favorable for using lenvatinib with pembrolizumab as first-line therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab with or Without Lenvatinib as First-line Therapy for Patients with Advanced Urothelial Carcinoma (LEAP-011): A Phase 3, Randomized, Double-Blind Trial. Matsubara, N., de Wit, R., Balar, AV., et al.[2023]

The combination of lenvatinib and pembrolizumab shows significant clinical benefits for patients with endometrial carcinoma, with a safety profile consistent with each drug's individual use, primarily involving manageable side effects like hypertension and hypothyroidism.

Effective management of lenvatinib's common adverse events is crucial to maximize its efficacy, as most side effects can be prevented or mitigated through proactive monitoring and intervention during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimizing the use of lenvatinib in combination with pembrolizumab in patients with advanced endometrial carcinoma. Lorusso, D., Danesi, R., Locati, LD., et al.[2023]

The combination of pembrolizumab and lenvatinib demonstrated significantly higher objective response rates (ORRs) and progression-free survival (mPFS) compared to their individual therapies in solid cancers, with ORRs reaching up to 70% in renal cell carcinoma.

Despite a high incidence of adverse events (68.0% for the combination therapy), the toxicities were manageable and no unexpected safety issues were reported, indicating that the combination therapy is both effective and relatively safe.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of pembrolizumab plus lenvatinib versus pembrolizumab and lenvatinib monotherapies in cancers: A systematic review. Mo, DC., Luo, PH., Huang, SX., et al.[2021]

The combination of lenvatinib, a multikinase inhibitor, and pembrolizumab, a PD-1 inhibitor, shows promising antitumor activity and durable responses in various solid tumors, as indicated by preliminary results from the LEAP clinical trial program.

This combination therapy has a manageable safety profile, suggesting it could be a valuable new treatment option for solid cancers that currently have limited therapeutic alternatives.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The LEAP program: lenvatinib plus pembrolizumab for the treatment of advanced solid tumors. Taylor, MH., Schmidt, EV., Dutcus, C., et al.[2021]

Citations

1. annalsofoncology.org annalsofoncology.org/article/S0923-7534(24)03200-9/fulltext

1600P Phase II trial of pembrolizumab and lenvatinib in ... Primary endpoint was 6- month radiologic progression-free survival (rPFS). Stud therapy was Lenvatinib 20 mg orally daily and intravenous pembrolizumab 200 mg ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.4_suppl.148

Pembrolizumab (pembro) plus lenvatinib (lenva) in patients ... Median OS was 9.4 months (95% CI, 8.4-NR); estimated 12-month OS rate was 37%. Treatment-related AEs (TRAEs) occurred in 92% of pts; most common ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38507897/

Phase II study of pembrolizumab and lenvatinib in ... Median progression-free survival (PFS) was 8 months (95% confidence interval 5.8-10.2 months). Twelve (60%) patients experienced probably or ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT02861573

NCT02861573 | Study of Pembrolizumab (MK-3475) ... The purpose of this study is to assess the safety and efficacy of pembrolizumab (MK-3475) combination therapy in participants with metastatic castration ...

5. esmoopen.com esmoopen.com/article/S2059-7029(24)00154-6/fulltext

Phase II study of pembrolizumab and lenvatinib in ... The combination of pembrolizumab and lenvatinib did not show sufficient response in patients with NETs to warrant continued enrollment on trial.

6. clinicaltrials.ucsf.edu clinicaltrials.ucsf.edu/trial/NCT05746208

Lenvatinib Plus Pembrolizumab in Well Differentiated G3 ... This is the first study to be done in a newly described class of neuroendocrine tumors known as well-differentiated grade 3 neuroendocrine tumors (WD G3 NET).

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10966166/

Phase II study of pembrolizumab and lenvatinib in advanced ... Pembrolizumab for patients with PD-L1–positive advanced carcinoid or pancreatic neuroendocrine tumors: results from the KEYNOTE-028 study.

8. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2023-01199

Lenvatinib and Pembrolizumab for the Treatment of Locally ... This phase II trial tests how well lenvatinib and pembrolizumab work in treating patients with well differentiated grade 3 neuroendocrine tumors.