Duvelisib + Nivolumab for Skin Cancer

Recruiting at 17 trial locations

Overseen By Jia Ruan

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: National Cancer Institute (NCI)

Must not be taking: CYP3A4 inhibitors, CYP3A4 inducers

Disqualifiers: Autoimmune disease, Hepatitis B/C, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 6

Duration: Up to 2 years

38 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests duvelisib and nivolumab in patients with advanced mycosis fungoides and Sezary syndrome. Duvelisib blocks cancer cell growth, and nivolumab boosts the immune system to fight cancer. The goal is to find the best dose and see if this combination works better than current treatments.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you must stop all current medications, but there are some restrictions. You cannot be on strong inhibitors or inducers of CYP3A4, and you must stop any systemic therapy for MF/SS with specific washout periods: 8 weeks for low-dose total skin electron beam therapy, 4 weeks for systemic cytotoxic agents or tumor-targeting monoclonal antibodies (except alemtuzumab, which is 16 weeks), 2 weeks or 5 half-lives for systemic retinoids and other specified agents, 2 weeks for local radiation, and 1 week for topical retinoids and other specified topical treatments. You can continue using inhaled steroids and certain topical steroids if stable for at least 4 weeks. Please consult with the trial team for guidance on your specific medications.

Will I have to stop taking my current medications?

The trial does not specify if you must stop all current medications, but you cannot take certain medications like strong inhibitors or inducers of CYP3A4, and some immunosuppressive drugs. There are specific 'washout' periods for certain treatments, such as 4 weeks for some anticancer agents and 1 week for topical treatments.

What data supports the idea that Duvelisib + Nivolumab for Skin Cancer is an effective treatment?

The available research shows that Nivolumab, one of the drugs in the Duvelisib + Nivolumab combination, has been effective in treating advanced melanoma, a type of skin cancer. It was the first drug of its kind to show long-term survival benefits in clinical trials for advanced melanoma patients. However, there is no specific data provided on the combination of Duvelisib and Nivolumab for skin cancer in the information available. ^{1 2 3 4 5}

What data supports the effectiveness of the drug combination Duvelisib and Nivolumab for skin cancer?

Nivolumab (Opdivo) has shown long-term survival benefits in patients with advanced melanoma, a type of skin cancer, as it was the first drug to demonstrate this in clinical trials. Additionally, Nivolumab has been effective in improving survival when used in combination with other drugs for different types of cancer, suggesting potential benefits when combined with Duvelisib for skin cancer. ^{1 2 3 4 5}

What safety data is available for the combination of Duvelisib and Nivolumab in treating skin cancer?

The provided research does not directly address the safety data for the combination of Duvelisib and Nivolumab specifically for skin cancer. However, it includes information on the safety profile of Nivolumab, which is used in combination therapies. Nivolumab has been associated with adverse reactions such as fatigue, diarrhea, constipation, nausea, musculoskeletal pain, rash, and pruritus. Additionally, dermatological adverse events have been reported with Nivolumab in combination with other drugs, such as rash and pruritus. No specific safety data for Duvelisib or its combination with Nivolumab is mentioned in the provided research. ^{6 7 8 9 10}

What safety information is available for the combination of Duvelisib and Nivolumab in humans?

Nivolumab, also known as Opdivo, has been associated with side effects like fatigue, diarrhea, constipation, nausea, muscle pain, rash, and itching. These side effects were observed in studies where Nivolumab was used alone or in combination with other drugs for different types of cancer. ^{6 7 8 9 10}

Is the drug Duvelisib, Nivolumab a promising treatment for skin cancer?

Yes, Nivolumab, which is part of the treatment, has shown promise in treating various cancers, including skin cancer. It works by helping the immune system fight cancer cells more effectively. In studies, it has improved survival rates and response in patients with advanced cancers. ^{1 8 11 12 13}

How is the drug combination of Duvelisib and Nivolumab unique for treating skin cancer?

The combination of Duvelisib and Nivolumab for skin cancer is unique because it combines a PI3K inhibitor (Duvelisib) with a PD-1 immune checkpoint inhibitor (Nivolumab), potentially enhancing the immune system's ability to fight cancer cells. This approach is different from traditional chemotherapy and surgery, offering a novel mechanism by targeting specific pathways involved in cancer growth and immune evasion. ^{1 8 11 12 13}

Research Team

Neha Mehta-Shah

Principal Investigator

Yale University Cancer Center LAO

Eligibility Criteria

Adults over 18 with stage IIB-IVB mycosis fungoides or Sezary syndrome who've had prior systemic therapy can join this trial. They must have certain levels of blood cells, kidney and liver function, and controlled brain metastases if present. Heart disease patients need a specific risk assessment. Participants must use effective contraception and not be pregnant or breastfeeding.

Inclusion Criteria

I can take care of myself but might not be able to do heavy physical work.

I am 18 years old or older.

Total bilirubin =< 1.5 x institutional upper limit of normal (ULN) or =< 5 x institutional ULN if with history of Gilbert's syndrome

Exclusion Criteria

I do not have an active or history of severe autoimmune disease.

I have been treated with a PI3K inhibitor before.

I have previously been treated with drugs that boost the immune system.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive duvelisib orally and nivolumab intravenously in 28-day cycles

Up to 2 years

Monthly visits for each cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

Every 6 months

Treatment Details

Interventions

• Duvelisib
• Nivolumab

Trial Overview The trial is testing the combination of duvelisib (which blocks enzymes for cell growth) with nivolumab (an immunotherapy that helps the immune system attack cancer). It aims to find the best dose, benefits, and side effects compared to usual treatments for these skin cancers.

Participant Groups

Group I: Treatment (duvelisib, nivolumab) Experimental Treatment 6 Interventions

Patients receive duvelisib PO QD or BID on days 1-28 or days 1-14 and nivolumab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo PET-CT or CT scan at baseline. Patients also undergo punch biopsy and collection of blood samples throughout the trial.

Duvelisib is already approved in United States for the following indications:

Approved in United States as Copiktra for:

• Relapsed or refractory chronic lymphocytic leukemia (CLL)
• Relapsed or refractory small lymphocytic lymphoma (SLL)

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Findings from Research

Nivolumab (Opdivo) monotherapy led to complete regression of local recurrence and multiple lung metastases in a patient with recurrent skin melanoma and a positive BRAF mutation, demonstrating its efficacy as a treatment option.

After 5 courses of nivolumab, the patient experienced significant improvement in her condition, achieving an ECOG performance status of 0, indicating a return to an active lifestyle without pain, and normal serum LDH levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[EVALUATION OF THE EFFICASY OF THE DRUG OPDIVO (NIVOLUMAB) IN A PATIENT DIAGNOSED WITH UNRESECTABLE SKIN MELANOMA, POSITIVE BRAF MUTATION AND DISEASE DISSEMINATION (CASE REPORT)]. Samsonia, M., Kandelaki, M., Gibradze, O., et al.[2021]

Nivolumab is shown to be the most cost-effective treatment option for advanced melanoma patients in England, with incremental cost-effectiveness ratios of £24,483 for BRAF mutation-negative and £17,362 for mutation-positive patients.

The analysis utilized a Markov state-transition model based on patient-level data from clinical trials, indicating that nivolumab provides long-term survival benefits while being economically favorable compared to other treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The cost-effectiveness of nivolumab monotherapy for the treatment of advanced melanoma patients in England. Meng, Y., Hertel, N., Ellis, J., et al.[2020]

In a study of 81 patients with unresectable locally advanced non-small cell lung cancer (NSCLC), those with high tumor mutational burden (TMB-high) showed significantly better outcomes, including lower local-regional failure rates (9% vs 51%) and improved progression-free survival (66% vs 27%) compared to TMB-low patients.

The study suggests that TMB status could be a valuable biomarker for personalizing treatment strategies, as it was the only factor significantly associated with local-regional failure and progression-free survival after treatment with chemoradiation and adjuvant durvalumab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Analysis of Tumor Mutational Burden, Progression-Free Survival, and Local-Regional Control in Patents with Locally Advanced Non-Small Cell Lung Cancer Treated With Chemoradiation and Durvalumab. Lebow, ES., Shepherd, A., Eichholz, JE., et al.[2023]

In a pooled analysis of 1332 patients with advanced non-small-cell lung cancer (NSCLC), the combination of nivolumab and ipilimumab showed a median overall survival (OS) of 18.6 months and a 3-year OS rate of 35%, indicating significant long-term survival benefits compared to traditional chemotherapy.

The study found that patients who responded to treatment at 6 months had markedly better survival rates, with a 3-year OS of 66% for responders, highlighting the importance of early response in predicting long-term outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term survival with first-line nivolumab plus ipilimumab in patients with advanced non-small-cell lung cancer: a pooled analysis. Borghaei, H., Ciuleanu, TE., Lee, JS., et al.[2023]

This phase I/II clinical trial is investigating the safety and efficacy of a combination treatment involving selumetinib, tremelimumab, and durvalumab in 40 patients with previously treated, unresectable non-small-cell lung cancer (NSCLC).

The study aims to determine the maximum tolerated dose and progression-free survival, while also exploring biomarkers of response and resistance, which could help tailor future treatments for NSCLC patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I/II Trial of Immunotherapy With Durvalumab and Tremelimumab With Continuous or Intermittent MEK Inhibitor Selumetinib in NSCLC: Early Trial Report. Gaudreau, PO., Lee, JJ., Heymach, JV., et al.[2021]

A review of 29 articles identified specific dermatological adverse events (AEs) associated with various immunotherapy combinations, highlighting that combinations like nivolumab/ipilimumab and lenvatinib/pembrolizumab had the highest incidence of rash.

Understanding these dermatological AEs, such as pruritus and alopecia, is crucial for optimizing treatment plans and improving patient monitoring during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dermatological adverse events associated with immune checkpoint inhibitor-based combinations of anticancer therapies: a systematic review. Salloum, A., Habre, M., Chebl, JA., et al.[2022]

Nivolumab significantly improved overall survival and progression-free survival in patients with unresectable or metastatic melanoma compared to dacarbazine, with hazard ratios of 0.42 and 0.43 respectively, based on a trial involving 418 patients.

The most common side effects of nivolumab included fatigue, diarrhea, and rash, but it was still considered to have a favorable benefit-risk profile compared to dacarbazine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval of Nivolumab for the First-Line Treatment of Patients with BRAFV600 Wild-Type Unresectable or Metastatic Melanoma. Beaver, JA., Theoret, MR., Mushti, S., et al.[2018]

Nivolumab, a PD-1 inhibitor used for advanced lung adenocarcinoma, can cause significant skin toxicity, as observed in a 60-year-old male patient who developed worsening skin rashes after treatment.

Early detection and treatment of immune-related skin toxicity with steroids led to alleviation of symptoms, suggesting that prompt management can improve patient outcomes while maintaining stable lung disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Treatment-related Skin Toxicity Caused by Programmed Death-1 Inhibitor Nivolumab: A Case Report]. Gao, L., Yu, Y., Lu, S.[2020]

In the Asian subpopulation with advanced non-small cell lung cancer (NSCLC) and PD-L1 expression ≥1%, patients treated with nivolumab plus ipilimumab showed significantly improved overall survival (OS) and progression-free survival (PFS) compared to those receiving chemotherapy, with a 3-year OS rate of 53% versus 37%.

The safety profile of nivolumab plus ipilimumab was manageable, with grade 3-4 treatment-related adverse events occurring in 40% of patients, similar to the 36% in the chemotherapy group, indicating no new safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-line nivolumab + ipilimumab in advanced NSCLC: CheckMate 227 subpopulation analyses in Asian patients. O'Byrne, KJ., Lee, KH., Kim, SW., et al.[2022]

The combination of durvalumab and tremelimumab in cancer treatment is associated with a higher incidence of severe adverse events (32.6%) compared to durvalumab alone (23.8%), indicating increased safety concerns with the combination therapy.

Patients receiving the combination therapy also experienced higher rates of specific side effects such as diarrhea (15.6% vs. 8.1%), rash (11.1% vs. 6.5%), and treatment discontinuation (18% vs. 3%), highlighting the need for careful monitoring and patient counseling regarding these risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse Events and Tolerability of Combined Durvalumab and Tremelimumab versus Durvalumab Alone in Solid Cancers: A Systematic Review and Meta-Analysis. Fahmy, O., Ahmed, OAA., Khairul-Asri, MG., et al.[2023]

Nivolumab, an immune checkpoint inhibitor, significantly improved overall survival and progression-free survival compared to docetaxel in patients with advanced squamous non-small cell lung cancer (NSCLC) in the CheckMate 017 trial.

Nivolumab was better tolerated than docetaxel, with manageable adverse effects, making it a promising treatment option for patients who have already undergone chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab: a review in advanced squamous non-small cell lung cancer. Keating, GM.[2022]

Nivolumab, a PD-1 inhibitor, has been FDA-approved for treating recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) after platinum-based therapy, but treatment options remain limited for these patients.

A case study of a 46-year-old male with refractory HNSCC showed successful treatment using a combination of nivolumab and ipilimumab, suggesting potential efficacy for this combination therapy in HNSCC, similar to its success in metastatic melanoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Successful Treatment of Refractory Squamous Cell Cancer of the Head and Neck with Nivolumab and Ipilimumab. Schwab, KS., Kristiansen, G., Schild, HH., et al.[2022]

Nivolumab, an immune checkpoint inhibitor, can lead to serious endocrine side effects, such as primary hypothyroidism, as seen in a case study of a young melanoma patient who developed symptoms after 12 weeks of treatment.

The patient's hypothyroidism was effectively managed with hormone replacement therapy, allowing him to continue nivolumab treatment safely, which underscores the importance of recognizing and managing endocrine-related adverse events to maintain patient safety and treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab-induced hypothyoidism with consequent hypothyroid related myopathy. Johnson, ED., Kerrigan, K., Butler, K., et al.[2020]

References

1. Georgia (Republic) pubmed.ncbi.nlm.nih.gov

[EVALUATION OF THE EFFICASY OF THE DRUG OPDIVO (NIVOLUMAB) IN A PATIENT DIAGNOSED WITH UNRESECTABLE SKIN MELANOMA, POSITIVE BRAF MUTATION AND DISEASE DISSEMINATION (CASE REPORT)]. [2021]

2. Germany pubmed.ncbi.nlm.nih.gov

The cost-effectiveness of nivolumab monotherapy for the treatment of advanced melanoma patients in England. [2020]

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

Analysis of Tumor Mutational Burden, Progression-Free Survival, and Local-Regional Control in Patents with Locally Advanced Non-Small Cell Lung Cancer Treated With Chemoradiation and Durvalumab. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Long-term survival with first-line nivolumab plus ipilimumab in patients with advanced non-small-cell lung cancer: a pooled analysis. [2023]

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

Phase I/II Trial of Immunotherapy With Durvalumab and Tremelimumab With Continuous or Intermittent MEK Inhibitor Selumetinib in NSCLC: Early Trial Report. [2021]

6. England pubmed.ncbi.nlm.nih.gov

Dermatological adverse events associated with immune checkpoint inhibitor-based combinations of anticancer therapies: a systematic review. [2022]

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

FDA Approval of Nivolumab for the First-Line Treatment of Patients with BRAFV600 Wild-Type Unresectable or Metastatic Melanoma. [2018]

8. China pubmed.ncbi.nlm.nih.gov

[Treatment-related Skin Toxicity Caused by Programmed Death-1 Inhibitor Nivolumab: A Case Report]. [2020]

9. England pubmed.ncbi.nlm.nih.gov

First-line nivolumab + ipilimumab in advanced NSCLC: CheckMate 227 subpopulation analyses in Asian patients. [2022]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Adverse Events and Tolerability of Combined Durvalumab and Tremelimumab versus Durvalumab Alone in Solid Cancers: A Systematic Review and Meta-Analysis. [2023]

11. New Zealand pubmed.ncbi.nlm.nih.gov

Nivolumab: a review in advanced squamous non-small cell lung cancer. [2022]

12. Switzerland pubmed.ncbi.nlm.nih.gov

Successful Treatment of Refractory Squamous Cell Cancer of the Head and Neck with Nivolumab and Ipilimumab. [2022]

13. England pubmed.ncbi.nlm.nih.gov

Nivolumab-induced hypothyoidism with consequent hypothyroid related myopathy. [2020]