Lenvatinib + Pembrolizumab for Anal Cancer

Overseen By Clinical Trials Intake

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Chicago

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: Infection, Immunodeficiency, Autoimmune, 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: 3

Duration: Up to 2 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test the safety and effectiveness of combining lenvatinib and pembrolizumab for treating anal or rectal cancer that has spread and does not respond to usual treatments. Patients take lenvatinib as a daily pill, while pembrolizumab is administered through an IV every three weeks. Individuals with advanced or metastatic anal cancer after initial treatment might be suitable candidates. Participants should have a cancer diagnosis that affects their daily life and should not have received similar treatments before. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, it mentions that participants on antiretroviral therapy for HIV must continue their regimen, and those with controlled blood pressure can stay on their antihypertensive medications.

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

Research has shown that the combination of lenvatinib and pembrolizumab has been tested for safety in various conditions. In one study, this combination achieved a 16.7% overall survival rate in patients with advanced endometrial cancer, indicating that patients could tolerate the treatment for an extended period.

Another study on uveal melanoma (a type of eye cancer) found the treatment promising, with some patients experiencing a significant period without cancer progression. However, safety remains a concern. Real-world data revealed that the side effects of this combination were similar to those observed in other clinical trials, indicating they were expected and not unusually severe.

These findings suggest that lenvatinib and pembrolizumab together are generally well-tolerated, but side effects can vary from person to person. It is important to consult a doctor when considering joining a trial. ^{1 2 3 4 5}

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

Researchers are excited about using lenvatinib and pembrolizumab for anal cancer because they offer a new approach compared to the standard treatments like chemoradiation. Lenvatinib is a targeted therapy that inhibits proteins involved in tumor growth, while pembrolizumab is an immunotherapy that helps the immune system recognize and attack cancer cells. This combination could potentially enhance the body’s ability to fight cancer more effectively than traditional methods, offering hope for better outcomes in patients.

What evidence suggests that lenvatinib combined with pembrolizumab might be an effective treatment for anal cancer?

Studies have shown that combining lenvatinib and pembrolizumab can improve outcomes for certain cancers. Research indicates that this combination increases the rate at which tumors shrink or stop growing. For example, some studies found that patients lived longer without their cancer worsening compared to those receiving standard treatments. This combination also lowered the risk of cancer spreading or leading to death in certain cancer types. While these results are promising, it is important to remember that every cancer is different, and the effectiveness of this treatment can vary from person to person. ^{1 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for patients with anal or rectal cancer that has spread and isn't responding to standard treatments. Specific eligibility details are not provided, but typically participants must meet certain health standards and have a type of cancer the study targets.

Inclusion Criteria

Written informed consent and HIPAA authorization for release of personal health information prior to registration

I have been mostly active and able to carry on all pre-disease activities without restriction recently.

I understand and can follow the study's procedures.

Exclusion Criteria

I have or had lung inflammation that needed steroids.

Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial

Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive lenvatinib (20 mg orally once daily) in combination with pembrolizumab (200 mg IV every 3 weeks) for a maximum of 2 years

Up to 2 years

Pembrolizumab every 3 weeks

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 is testing the combination of two drugs, Lenvatinib and Pembrolizumab, to evaluate their safety and effectiveness in treating advanced anal or rectal cancer that's resistant to initial treatments.

How Is the Trial Designed?

Group I: Treatment arm Experimental Treatment 2 Interventions

Treatment consists of lenvatinib (20 mg orally once daily) in combination with pembrolizumab (200 mg IV every 3 weeks). Pembrolizumab will be given for a maximum of 2 years (total 35 cycles) with dosing every 3 weeks.

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 Chicago

Lead Sponsor

Trials

1,086

Recruited

844,000+

Published Research Related to This Trial

In a phase 1b study involving 6 Japanese patients with metastatic solid tumors, the combination of lenvatinib and pembrolizumab was well-tolerated, with no dose-limiting toxicities reported.

The treatment showed promising antitumor activity, with an objective response rate of 33.3%, particularly in patients with urothelial cancer, indicating potential efficacy for this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A feasibility study of lenvatinib plus pembrolizumab in Japanese patients with advanced solid tumors. Kitano, S., Fujiwara, Y., Shimizu, T., et al.[2022]

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]

In a study of 43 patients with recurrent endometrial cancer treated with lenvatinib and pembrolizumab, 84% experienced significant adverse events (AEs), with hypertension and weight loss being the most common.

Patients starting on a reduced dose of lenvatinib (10 mg or 14 mg) had significantly longer progression-free survival compared to those on the standard dose (20 mg), suggesting that dose optimization may improve treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events and oncologic outcomes with combination lenvatinib and pembrolizumab for the treatment of recurrent endometrial cancer. Zammarrelli, WA., Ma, W., Espino, K., et al.[2023]

In a phase 2 trial involving 29 patients with advanced gastric cancer, the combination of lenvatinib and pembrolizumab resulted in a promising objective response rate of 69%, indicating significant anti-tumor activity.

The treatment was generally well-tolerated, with the most common grade 3 adverse events being manageable, such as hypertension and proteinuria, and no serious treatment-related complications or deaths reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenvatinib plus pembrolizumab in patients with advanced gastric cancer in the first-line or second-line setting (EPOC1706): an open-label, single-arm, phase 2 trial. Kawazoe, A., Fukuoka, S., Nakamura, Y., et al.[2020]

Combination therapy with pembrolizumab and lenvatinib is effective as a first-line treatment for clear cell renal carcinoma and as a second-line option for recurrent or metastatic endometrial carcinoma, based on data from five completed clinical trials and two ongoing trials.

This non-chemotherapy regimen helps spare patients from prolonged myelosuppression and lowers the risk of infection, making it a safer alternative for cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined use of pembrolizumab and lenvatinib: A review. Eisinger, C., Muluneh, B.[2023]

In a study of 7 women with advanced or recurrent uterine carcinosarcoma (UCS) treated with pembrolizumab and lenvatinib, the combination therapy showed limited efficacy, with no observed partial or complete responses.

The median progression-free survival (PFS) was only 2.6 months and overall survival (OS) was 2.8 months, suggesting that this treatment may not be more effective than traditional chemotherapy options for UCS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenvatinib plus pembrolizumab in patients with advanced or recurrent uterine carcinosarcoma. Hunt, JT., Chambers, LM., Yao, M., et al.[2022]

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 pembrolizumab and lenvatinib has shown promising efficacy in treating advanced endometrial cancer, with previous trials indicating improved objective response rates and survival outcomes compared to standard chemotherapy.

This ongoing phase 3 trial aims to determine if pembrolizumab plus lenvatinib is superior to the chemotherapy regimen of paclitaxel plus carboplatin in newly diagnosed patients, with a target enrollment of about 875 participants and results expected in 2022.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 3, randomized, open-label study of pembrolizumab plus lenvatinib versus chemotherapy for first-line treatment of advanced or recurrent endometrial cancer: ENGOT-en9/LEAP-001. Marth, C., Tarnawski, R., Tyulyandina, A., et al.[2022]

In a phase 2 study involving 112 patients with advanced anal squamous cell carcinoma, pembrolizumab demonstrated an objective response rate of 11%, with a higher response (15%) in patients with PD-L1-positive tumors, indicating its potential efficacy in this difficult-to-treat cancer.

The treatment was generally well-tolerated, with 61% of patients experiencing treatment-related adverse events, but no treatment-related deaths were reported, suggesting a favorable safety profile for pembrolizumab in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for previously treated advanced anal squamous cell carcinoma: results from the non-randomised, multicohort, multicentre, phase 2 KEYNOTE-158 study. Marabelle, A., Cassier, PA., Fakih, M., et al.[2022]

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]

In a study of 70 patients with recurrent endometrial cancer, a lower starting dose of lenvatinib (14 mg daily) combined with pembrolizumab was found to be safe and effective, showing similar response rates compared to the recommended dose (20 mg).

Patients with carcinosarcoma histology experienced notable clinical benefits, with a response rate of 25% and a clinical benefit rate of 58.3%, indicating that this treatment combination may be particularly effective for this subtype of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toxicity and efficacy of the combination of pembrolizumab with recommended or reduced starting doses of lenvatinib for treatment of recurrent endometrial cancer. How, JA., Patel, S., Fellman, B., et al.[2022]

Citations

1. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK603321/

Pembrolizumab + Lenvatinib: Combination Therapy Treatment with PEM-LEN also showed a statistically significant and clinically meaningful improvement in objective response rate (ORR) (ORR = 30.3% and 15.1% ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.23.02736

Lenvatinib Plus Pembrolizumab Versus Standard of Care ... In the LEAP-017 study, we evaluate whether lenvatinib in combination with pembrolizumab improves outcomes compared with standard of care (SOC) ...

3. merck.com merck.com/news/keytruda-pembrolizumab-plus-lenvima-lenvatinib-in-combination-with-transarterial-chemoembolization-significantly-improved-progression-free-survival-compared-to-tace-alone-in-patients-w/

KEYTRUDA + LENVIMA Improves PFS in HCC vs TACE Alone KEYTRUDA plus LENVIMA in combination with TACE reduced the risk of disease progression or death by 34% compared to TACE alone.

4. media-us.eisai.com media-us.eisai.com/2020-09-10-Eisai-to-Present-New-Data-Highlighting-KEYTRUDA-R-pembrolizumab-plus-LENVIMA-R-lenvatinib-Investigational-Combination-Therapy-and-Eribulin-Platform-at-ESMO-2020

Eisai to Present New Data Highlighting KEYTRUDA ... Safety and effectiveness of LENVIMA in patients with ATC have not been demonstrated in clinical trials. Consider the risk of severe or fatal ...

5. targetedonc.com targetedonc.com/view/lenvatinib-pembrolizumab-shows-positive-trends-vs-global-soc-in-frontline-rcc-meta-analysis

Lenvatinib/Pembrolizumab Shows Positive Trends vs ... First-line lenvatinib and pembrolizumab showed similar overall survival rates and improved progression-free survival and response rates vs global standard-of- ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38833658/

Lenvatinib Plus Pembrolizumab Versus Standard of Care ... In the LEAP-017 study, we evaluate whether lenvatinib in combination with pembrolizumab improves outcomes compared with standard of care (SOC) in previously ...

7. targetedonc.com targetedonc.com/view/pembrolizumab-plus-lenvatinib-shows-encouraging-efficacy-in-uveal-melanoma

Pembrolizumab Plus Lenvatinib Shows Encouraging ... Pembrolizumab and lenvatinib showed promising PFS in uveal melanoma patients, with 31.8% and 60.7% rates in different cohorts. The safety ...

8. merck.com merck.com/news/keytruda-pembrolizumab-plus-lenvima-lenvatinib-demonstrates-durable-5-year-survival-benefit-versus-chemotherapy-for-patients-with-advanced-endometrial-carcinoma-following-one-prior-pla/

KEYTRUDA® (pembrolizumab) Plus LENVIMA® ... At five years, KEYTRUDA plus LENVIMA showed a 16.7% overall survival (OS) rate for these patients with mismatch repair proficient (pMMR) advanced ...

9. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0936655524004217

Real World Outcomes in Patients With Recurrent ... This real-world, observational study of pem/len showed comparable tolerability, toxicity and outcomes to previously reported clinical trial data.