Pembrolizumab + Lenvatinib for Neuroendocrine Prostate Cancer

(PLANE-PC Trial)

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)

50 Participants Needed

Trial Summary

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 the combination of pembrolizumab and lenvatinib generally safe for humans?

The combination of pembrolizumab and lenvatinib has been shown to have a manageable safety profile in various cancers, with common side effects including high blood pressure, low thyroid function, diarrhea, nausea, vomiting, loss of appetite, fatigue, and weight loss. ^{1 2 3 4 5}

What makes the drug combination of Pembrolizumab and Lenvatinib unique for treating neuroendocrine prostate cancer?

The combination of Pembrolizumab and Lenvatinib is unique for treating neuroendocrine prostate cancer because it combines an immune checkpoint inhibitor (Pembrolizumab) with a targeted therapy (Lenvatinib) that may help overcome the limited efficacy of immunotherapy alone in this aggressive cancer type, offering a novel approach to a condition with few effective treatments. ^{6 7 8 9 10}

What is the purpose of this trial?

This trial uses a combination of two drugs, lenvatinib and pembrolizumab, to treat patients with cancer that hasn't responded to other treatments. Lenvatinib stops cancer cells from growing, while pembrolizumab helps the immune system attack the cancer. The combination received accelerated FDA approval in September 2019 for all patients with advanced endometrial cancer who have disease progression following previous treatments. The treatment cycles last a few weeks and can continue for several months unless there are side effects or other reasons to stop.

Research Team

Ulka Vaishampayan, MD

Principal Investigator

University of Michigan

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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, 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]

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]

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 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]

References

1. Switzerland 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. [2023]

2. England pubmed.ncbi.nlm.nih.gov

The LEAP program: lenvatinib plus pembrolizumab for the treatment of advanced solid tumors. [2021]

3. England 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. [2023]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Safety and efficacy of pembrolizumab plus lenvatinib versus pembrolizumab and lenvatinib monotherapies in cancers: A systematic review. [2021]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Optimizing the use of lenvatinib in combination with pembrolizumab in patients with advanced endometrial carcinoma. [2023]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Targeting Key Players of Neuroendocrine Differentiation in Prostate Cancer. [2023]

7. United States pubmed.ncbi.nlm.nih.gov

Review of Checkpoint Inhibitor Immunotherapy in Neuroendocrine Tumor of Prostate and Our Experience in 2 Cases. [2023]

8. Switzerland pubmed.ncbi.nlm.nih.gov

High-throughput drug screening identifies fluoxetine as a potential therapeutic agent for neuroendocrine prostate cancer. [2023]

9. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Systems Medicine Approaches to Improving Understanding, Treatment, and Clinical Management of Neuroendocrine Prostate Cancer. [2019]

10. United States pubmed.ncbi.nlm.nih.gov

The central role of Sphingosine kinase 1 in the development of neuroendocrine prostate cancer (NEPC): A new targeted therapy of NEPC. [2022]