Pembrolizumab + Chemotherapy + Radiation for Anal Cancer

Recruiting at 3 trial locations

Overseen By Rebecca Mottier

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Dustin Deming

Must not be taking: Immunosuppressants, Live vaccines

Disqualifiers: Uncontrolled illness, Active CNS metastases, Autoimmune disease, 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

Compensation: Varies

Number of Visits: 14

23 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a combination of pembrolizumab (an immunotherapy drug), carboplatin, paclitaxel, and radiation to treat early-stage anal cancer. The goal is to determine if this combination can effectively target the cancer. The trial consists of two phases: an initial phase where treatments occur weekly alongside radiation, followed by a maintenance phase with treatments every six weeks. Individuals with early-stage anal cancer who cannot receive the standard treatment with certain other drugs might be suitable candidates for this trial. 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 protocol does not specify if you must stop taking your current medications. However, if you are on a medication that is contraindicated (not allowed) with the study drugs, you may need to stop or switch to an alternative within 7 days before starting the trial.

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

Research has shown that the combination of pembrolizumab, carboplatin, and paclitaxel has been studied for safety. In past studies, most patients tolerated this treatment well. Common side effects included nausea and tiredness, typical with chemotherapy.

More serious side effects were less common but did occur, such as low blood cell counts, which can increase infection risk, and some liver problems. Pembrolizumab is already approved for other cancers, so its safety profile is well-understood.

Overall, while risks exist, the treatment's safety has been carefully studied, and many side effects can be managed with medical care. Prospective trial participants should discuss these details with the trial team or their doctor. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for anal cancer?

Researchers are excited about the combination of pembrolizumab with chemotherapy and radiation for anal cancer because pembrolizumab is an immunotherapy that works by engaging the immune system to target cancer cells more effectively. Unlike traditional treatments that primarily rely on chemotherapy and radiation alone, pembrolizumab specifically blocks a protein called PD-1, helping immune cells better recognize and attack cancer. This approach could potentially enhance the effectiveness of standard treatments like carboplatin and paclitaxel, offering a more powerful and targeted attack on cancer cells. Moreover, by integrating the maintenance phase with pembrolizumab, there's hope for sustained cancer control beyond the initial treatment.

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

Studies have shown positive results for using pembrolizumab with carboplatin, paclitaxel, and radiation to treat anal cancer. Research indicates that this combination can lead to good complete response rates, meaning the cancer might completely disappear after treatment. All participants in this trial will receive this combination during the chemoradiation phase. Pembrolizumab, a type of immunotherapy, helps the immune system attack cancer cells more effectively. Previous patients with advanced anal cancer demonstrated promising outcomes with pembrolizumab, suggesting it could work well in earlier stages too. Overall, the evidence supports the potential effectiveness of this treatment combination for early-stage anal cancer. ^{1 2 3 6 7}

Who Is on the Research Team?

Dustin Deming, M.D.

Principal Investigator

University of Wisconsin, Madison

Are You a Good Fit for This Trial?

This trial is for individuals with early-stage anal cancer. Participants should be suitable for chemotherapy and radiation, but specific inclusion and exclusion criteria details are not provided.

Inclusion Criteria

1. Written informed consent and HIPAA authorization for release of personal health information. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.

3. ECOG Performance Status of 0-1 within 30 days prior to registration.

4. Histologically proven stage I (T1N0), IIA (T2N0), IIB (T1/2N1), or IIIA (T3 N0/1) invasive squamous cell carcinoma of the anus by AJCC version 9.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Chemoradiation

Participants receive a combination of pembrolizumab, carboplatin, paclitaxel, and radiation. Carboplatin and paclitaxel are administered weekly, and pembrolizumab is administered on cycles 1 and 4.

6 weeks

6 visits (in-person)

Maintenance

Participants receive pembrolizumab every 6 weeks for 8 cycles.

48 weeks

8 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of treatment emergent toxicities and overall response rate.

3 years

What Are the Treatments Tested in This Trial?

Interventions

• Carboplatin
• Paclitaxel
• Pembrolizumab
• Radiation

Trial Overview The study tests a combination of pembrolizumab (an immunotherapy drug), carboplatin, paclitaxel (chemotherapy drugs), and radiation therapy in two phases: chemoradiation followed by maintenance, to treat early-stage anal cancer.

How Is the Trial Designed?

Group I: Pembrolizumab plus carbopltin and paclitaxel Experimental Treatment 4 Interventions

All patients in the chemoradiation phase will receive a combination of pembrolizumab, carboplatin, and paclitaxel. For the first 6 cycles (a cycle is a week) carboplatin and paclitaxel will be administered by IV every week. Pembrolizumab will be administered by IV on cycles 1 and 4. The next phase is the maintenance phase. This will occur from cycle 7-14 with each cycle being 6 weeks. Pembrolizumab will be administered every cycle.

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

Approved in United States as Paraplatin for:

• Ovarian cancer
• Testicular cancer
• Lung cancer
• Head and neck cancer
• Brain cancer

Approved in European Union as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer

Approved in Canada as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer
• Testicular cancer

Who Is Running the Clinical Trial?

Dustin Deming

Lead Sponsor

Trials

1

Recruited

20+

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 Wisconsin, Madison

Collaborator

Trials

1,249

Recruited

3,255,000+

Published Research Related to This Trial

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]

In a phase Ib trial (KEYNOTE-028) involving 43 patients with advanced anal carcinoma, pembrolizumab showed a manageable safety profile, with 64% experiencing treatment-related adverse events, but no treatment-related deaths or discontinuations.

Among patients with PD-L1-positive tumors, pembrolizumab achieved a 17% overall response rate and a 58% disease control rate, indicating promising antitumor activity and supporting further research in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and antitumor activity of the anti-PD-1 antibody pembrolizumab in patients with recurrent carcinoma of the anal canal. Ott, PA., Piha-Paul, SA., Munster, P., et al.[2021]

The combination of pembrolizumab with chemoradiation for muscle-invasive bladder cancer (MIBC) was found to be feasible, with manageable toxicity, as only six patients experienced grade 3 or worse nonurinary adverse events out of 28 participants in the study.

The treatment showed promising efficacy, with an 88% complete response rate at 24 weeks post-chemoradiation, and favorable survival rates, including a 2-year distant metastasis-free survival rate of 78% and locoregional progression-free survival rate of 87%.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab with Chemoradiation as Treatment for Muscle-invasive Bladder Cancer: Analysis of Safety and Efficacy of the PCR-MIB Phase 2 Clinical Trial (ANZUP 1502). Weickhardt, A., Foroudi, F., Lawrentschuk, N., et al.[2023]

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]

Pembrolizumab, an immune checkpoint inhibitor, can cause pneumonitis in 1%-5% of patients, and this case report highlights an atypical presentation of this side effect in a patient with metastatic squamous cell carcinoma.

The patient was successfully treated with steroid therapy after ruling out other potential causes, leading to complete resolution of the pneumonitis, emphasizing the importance of recognizing and managing atypical cases of checkpoint inhibitor-pneumonitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. Jeon, WJ., Nguyen, J., Castillo, DR., et al.[2023]

In a study of 98 advanced urothelial cancer patients, those who received radiotherapy to the primary tumor showed a significantly higher objective response rate to pembrolizumab (65% vs 19%) compared to those who did not receive radiotherapy.

Patients who had prior radiotherapy also experienced better overall survival rates (77% vs 50% at 12 months), suggesting that radiotherapy may enhance the effectiveness of pembrolizumab in treating advanced urothelial cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of radiotherapy to the primary tumor on the efficacy of pembrolizumab for patients with advanced urothelial cancer: A preliminary study. Fukushima, H., Kijima, T., Fukuda, S., et al.[2023]

In a phase 2 study involving 216 patients with stage III non-small cell lung cancer (NSCLC), the combination of pembrolizumab and concurrent chemoradiation therapy (cCRT) showed a high objective response rate of approximately 70.5% in cohort A and 70.6% in cohort B, indicating strong antitumor activity.

The treatment was associated with manageable safety, with grade 3 or higher pneumonitis occurring in 8.0% of cohort A and 6.9% of cohort B, suggesting that while there are risks, the benefits of this treatment approach may outweigh them for patients with locally advanced NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab Plus Concurrent Chemoradiation Therapy in Patients With Unresectable, Locally Advanced, Stage III Non-Small Cell Lung Cancer: The Phase 2 KEYNOTE-799 Nonrandomized Trial. Jabbour, SK., Lee, KH., Frost, N., et al.[2022]

In a phase II study involving 29 patients with locally advanced head and neck squamous cell carcinoma who were ineligible for cisplatin, the combination of pembrolizumab and radiotherapy showed promising efficacy, with a 24-month progression-free survival rate of 71%.

The treatment was generally well-tolerated, although a significant number of patients experienced grade 3/4 lymphopenia (58.6%), indicating the need for monitoring immune cell changes during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Concurrent Definitive Immunoradiotherapy for Patients with Stage III-IV Head and Neck Cancer and Cisplatin Contraindication. Weiss, J., Sheth, S., Deal, AM., et al.[2023]

Pembrolizumab, an anti-PD-1 antibody used for treating various cancers, can cause immune-related adverse events (IRAEs) affecting multiple body systems, including rare oral mucosal issues like glossitis.

In a case study of a 71-year-old male with lung cancer, treatment with oral prednisone effectively improved tongue ulcerations caused by pembrolizumab, highlighting the need for awareness of such rare side effects and their management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab-Induced Immune-Mediated Glossitis. Alias, A., Hall, JA., Kulkarni, P., et al.[2022]

A 74-year-old woman with lung adenocarcinoma developed fatal immune thrombocytopenia after receiving pembrolizumab following radiotherapy, highlighting a potential risk of severe immune-related adverse events (irAEs) when combining these treatments.

Flow cytometry analysis showed increased PD-1 and Ki-67 expression in T cells post-radiotherapy, suggesting that radiotherapy may enhance immune activation and contribute to the development of irAEs in patients undergoing anti-PD-1 therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab-related Immune Thrombocytopenia in a Patient with Lung Adenocarcinoma Treated by Radiotherapy: Potential Immune-related Adverse Event Elicited by Radiation Therapy. Tamanoi, D., Saruwatari, K., Imamura, K., et al.[2022]

In a trial involving 25 patients with locally advanced non-small-cell lung cancer (LA-NSCLC) and a PD-L1 tumor proportion score of ≥50%, the combination of pembrolizumab and risk-adapted radiotherapy achieved a 1-year progression-free survival rate of 76%, indicating strong efficacy without the use of chemotherapy.

The treatment was well-tolerated, with only 8% of patients experiencing grade 3 adverse events like colitis and esophagitis, and no higher-grade treatment-related adverse events reported, suggesting a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Selective Personalized Radioimmunotherapy for Locally Advanced Non-Small-Cell Lung Cancer Trial. Ohri, N., Jolly, S., Cooper, BT., et al.[2023]

Pembrolizumab has been approved by the FDA as the first-line treatment for both HPV-positive and HPV-negative recurrent head and neck squamous cell carcinoma, marking it as a significant advancement in immunotherapy for this cancer type.

The approval allows pembrolizumab to be used either alone for tumors expressing PD-L1 or in combination with chemotherapy, highlighting the need for healthcare providers to be aware of and manage potential immune-related toxicities such as dermatitis and mucositis associated with this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of Immune-Related Dermatitis and Mucositis Associated With Pembrolizumab in Metastatic Human Papillomavirus-Associated Squamous Cell Carcinoma of the Oropharynx. Fazer, C., Price, KA.[2021]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.TPS3633

A phase II study of pembrolizumab, carboplatin, paclitaxel ... Building on pilot data demonstrating favorable clinical complete responses (cCR) with carboplatin and paclitaxel combined with radiation in ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06493019

NCT06493019 | Study of Pembrolizumab, Carboplatin ... Assess the overall response rate of weekly carboplatin and paclitaxel in combination with pembrolizumab and radiation for the treatment of anal cancer.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10824013/

analysis of a phase II clinical trial and a cohort of long-term ... Herein, we report the results of a phase II trial of pembrolizumab in 32 patients with advanced anal squamous cell carcinoma, along with a 19- ...

4. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2024-06513

Pembrolizumab, Carboplatin, Paclitaxel, and Radiation for ... This phase II trial tests how well pembrolizumab, carboplatin, paclitaxel and radiation works in treating patients with early stage anal cancer.

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. merck.com merck.com/news/five-year-data-for-mercks-keytruda-pembrolizumab-plus-chemotherapy-showed-sustained-survival-benefit-versus-chemotherapy-alone-in-two-studies-for-metastatic-non-small-cell-lung-cancer-nsclc/

Five-Year Data for Merck's KEYTRUDA® (pembrolizumab ... Five-year overall survival rate of 19.4% and 18.4% for KEYTRUDA plus chemotherapy in KEYNOTE-189 and KEYNOTE-407, respectively.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12012850/

Pembrolizumab for previously treated advanced anal ... We evaluated the efficacy and safety of pembrolizumab in patients with advanced anal squamous cell carcinoma (cohort A) from the phase 2 KEYNOTE-158 study.