Fasting + PD-1/PD-L1 Inhibitors for Skin Cancer

Recruiting at 2 trial locations

Overseen By Charlean Ketchens, RN

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Southern California

Must be taking: PD-1/PD-L1 inhibitors

Must not be taking: Diabetes medications, Immunosuppressive corticosteroids

Disqualifiers: Diabetes, Brain metastases, Autoimmune disease, others

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 3

Duration: 9 weeks

10 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial studies the side effects of short-term fasting in patients with skin malignancy that has spread to other places in the body (advanced or metastatic) treated with a PD-L1 or PD-1 inhibitor. Immunotherapy with monoclonal antibodies, such as pembrolizumab, nivolumab, cemiplimab, avelumab, atezolizumab, or durvalumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Undergoing short-term fasting prior to treatment with one of these PD-L1 or PD-1 inhibitors may potentially reduce the side effects of immunotherapy or even improve the effectiveness of immunotherapy in patients with skin malignancy.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications, but it mentions that subjects on medications that cannot be safely stopped during fasting or consumed without food are excluded. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drugs used in the Fasting + PD-1/PD-L1 Inhibitors for Skin Cancer trial?

Research shows that pembrolizumab, one of the drugs in the trial, has been effective in treating advanced skin cancers like melanoma and cutaneous squamous cell carcinoma, with significant antitumor activity and manageable safety. Avelumab, another drug in the trial, is approved for treating metastatic Merkel cell carcinoma, demonstrating its effectiveness in aggressive skin cancers. ^{1 2 3 4 5}

Is the combination of fasting and PD-1/PD-L1 inhibitors safe for humans?

Research on PD-1/PD-L1 inhibitors like atezolizumab and pembrolizumab shows they are generally safe for treating conditions like melanoma and head and neck cancer, though they can have side effects. These studies provide safety data for these drugs, but the specific combination with fasting hasn't been directly studied for safety. ^{2 6 7 8 9}

How is the drug combination of fasting and PD-1/PD-L1 inhibitors unique for treating skin cancer?

This treatment combines fasting with PD-1/PD-L1 inhibitors, which are drugs that help the immune system attack cancer cells by blocking proteins that stop immune cells from killing cancer. This approach is unique because it explores the potential benefits of fasting to enhance the effectiveness of these immune-boosting drugs in treating skin cancer. ^{2 6 10 11 12}

Research Team

Gino K. In

Principal Investigator

University of Southern California

Eligibility Criteria

This trial is for adults with advanced or metastatic skin cancer recommended to receive PD-1/PD-L1 inhibitor immunotherapy. They must have adequate organ function, no more than two prior systemic therapies, and a good performance status. Women and men should agree to use contraception during the study. Exclusions include allergies to similar drugs, diabetes, recent significant weight loss without clear cause, other ongoing treatments or surgeries, active autoimmune diseases requiring treatment in the past 2 years, brain metastases, uncontrolled illnesses that could affect compliance.

Inclusion Criteria

I have had 2 or fewer treatments for my cancer, not counting initial treatments.

You have a sufficient number of a type of white blood cell called lymphocytes in your blood.

Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 90 days following completion of therapy. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately

Exclusion Criteria

I haven't had radiation or certain drug treatments in the last 4 weeks.

I have been treated with drugs that target PD-1 or PD-L1.

You had allergic reactions to drugs similar to the PD-1 or PD-L1 inhibitor.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo short-term fasting for 47-48 hours prior to and 24 hours after immunotherapy with PD-1/PD-L1 inhibitors. Treatment repeats every 21 days for up to 3 cycles.

9 weeks

3 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

3-6 weeks

Treatment Details

Interventions

• Atezolizumab
• Avelumab
• Cemiplimab
• Nivolumab
• Pembrolizumab
• Short-Term Fasting

Trial Overview The trial tests if short-term fasting before taking PD-1/PD-L1 inhibitors (like pembrolizumab or atezolizumab) can reduce side effects and improve effectiveness against advanced skin malignancy. It studies how well patients tolerate fasting combined with these immunotherapies which are designed to boost the immune system's ability to fight cancer.

Participant Groups

Group I: Treatment (STF, PD-1/PD-L1 inhibitor) Experimental Treatment 8 Interventions

Patients undergo STF for 47-48 hours prior to immunotherapy and for 24 hours after immunotherapy with standard of care pembrolizumab given IV over 30 minutes, nivolumab IV over 30 minutes, cemiplimab IV over 30 minutes, avelumab IV over 60 minutes, atezolizumab IV over 60 minutes, or durvalumab IV over 60 minutes on day 3. Treatment repeats every 21 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity.

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

Approved in United States as Tecentriq for:

• Melanoma
• Hepatocellular carcinoma
• Small cell lung cancer
• Non-small cell lung cancer
• Urothelial carcinoma

Approved in European Union as Tecentriq for:

• Melanoma
• Hepatocellular carcinoma
• Small cell lung cancer
• Non-small cell lung cancer
• Urothelial carcinoma

Who Is Running the Clinical Trial?

University of Southern California

Lead Sponsor

Trials

956

Recruited

1,609,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

In a phase II trial involving 159 patients with locally advanced or recurrent/metastatic cutaneous squamous cell carcinoma, pembrolizumab showed significant antitumor activity, with an objective response rate of 50.0% in the locally advanced cohort and 35.2% in the recurrent/metastatic cohort.

The treatment demonstrated a manageable safety profile, with only 11.9% of patients experiencing grade 3-5 treatment-related adverse events, indicating that pembrolizumab is a promising and durable treatment option for cSCC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for locally advanced and recurrent/metastatic cutaneous squamous cell carcinoma (KEYNOTE-629 study): an open-label, nonrandomized, multicenter, phase II trial. Hughes, BGM., Munoz-Couselo, E., Mortier, L., et al.[2022]

In a randomized trial comparing FDA-approved immune checkpoint inhibitors for advanced melanoma, pembrolizumab showed significantly better treatment outcomes than ipilimumab.

This study is notable as it is the first to directly compare these two therapies as first-line treatments, highlighting pembrolizumab's potential as a more effective option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab superior to ipilimumab in melanoma. [2017]

In a study of 39 patients with unresectable cutaneous squamous cell carcinomas (CSCCs), first-line treatment with pembrolizumab showed an objective response rate of 41% at week 15, indicating significant anti-tumor activity, especially in patients with PD-L1 positive tumors (55% response rate).

The treatment was generally well-tolerated, with 71% of patients experiencing adverse events, but only 7% had severe (grade ≥ 3) side effects, suggesting that pembrolizumab has a manageable safety profile while providing durable responses in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II Study of Pembrolizumab As First-Line, Single-Drug Therapy for Patients With Unresectable Cutaneous Squamous Cell Carcinomas. Maubec, E., Boubaya, M., Petrow, P., et al.[2021]

In a phase II trial involving 116 patients with metastatic Merkel cell carcinoma (mMCC), first-line treatment with avelumab resulted in a 39.7% objective response rate and a 30.2% durable response rate, indicating its efficacy in this aggressive skin cancer.

The treatment was generally well-tolerated, with 81% of patients experiencing treatment-related adverse events, but only 18.1% had severe (grade 3/4) events, and there were no treatment-related deaths, highlighting its safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-line avelumab in a cohort of 116 patients with metastatic Merkel cell carcinoma (JAVELIN Merkel 200): primary and biomarker analyses of a phase II study. D'Angelo, SP., Lebbé, C., Mortier, L., et al.[2022]

Atezolizumab, an anti-PD-L1 therapy, was well tolerated in a study of 45 patients with advanced melanoma, showing that most side effects were mild (grade 1/2) and no treatment-related deaths occurred.

The treatment resulted in a 30% overall response rate and a median overall survival of 23 months, with certain biomarkers like PD-L1 expression and tumor mutational burden linked to better outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, Clinical Activity, and Biological Correlates of Response in Patients with Metastatic Melanoma: Results from a Phase I Trial of Atezolizumab. Hamid, O., Molinero, L., Bolen, CR., et al.[2020]

In a study of 655 patients with advanced melanoma, pembrolizumab showed a 5-year overall survival rate of 34%, with even better outcomes (41%) for treatment-naive patients, indicating its long-term efficacy.

The treatment was generally well-tolerated, with 86% of patients experiencing treatment-related adverse events, but only 7.8% discontinued due to these effects, suggesting a manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Five-year survival outcomes for patients with advanced melanoma treated with pembrolizumab in KEYNOTE-001. Hamid, O., Robert, C., Daud, A., et al.[2023]

In a study of 88 advanced melanoma patients treated with pembrolizumab, 81.8% experienced any-grade toxicities, with skin and gastrointestinal issues being the most common side effects.

Despite the high incidence of side effects, pembrolizumab was found to be well tolerated in real-world settings, and severe toxicities were manageable with systemic steroids.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world experience with pembrolizumab toxicities in advanced melanoma patients: a single-center experience in the UK. So, AC., Board, RE.[2022]

In a phase Ia clinical trial involving 32 patients with advanced head and neck cancer, atezolizumab demonstrated a tolerable safety profile, with 66% of patients experiencing treatment-related adverse events, but no grade 5 events reported.

The treatment showed promising efficacy, with 22% of patients achieving objective responses and a median overall survival of 6.0 months, indicating potential benefits regardless of HPV status or PD-L1 expression levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and clinical activity of atezolizumab in head and neck cancer: results from a phase I trial. Colevas, AD., Bahleda, R., Braiteh, F., et al.[2022]

Cemiplimab is currently the only FDA-approved anti-PD1 agent for treating locally advanced or metastatic cutaneous squamous cell carcinoma (SCC), providing a new option for patients who cannot undergo surgery.

Other anti-PD1 agents like pembrolizumab and nivolumab have shown promising results in reducing tumor size in advanced SCC with minimal side effects, highlighting the potential of immunotherapy for patients who do not respond to traditional treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-PD1 Agents in the Treatment of Cutaneous Squamous Cell Carcinoma. Niu, W., Robertson, C., Hilton, D.[2023]

References

1. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab for locally advanced and recurrent/metastatic cutaneous squamous cell carcinoma (KEYNOTE-629 study): an open-label, nonrandomized, multicenter, phase II trial. [2022]

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

Pembrolizumab superior to ipilimumab in melanoma. [2017]

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

Phase II Study of Pembrolizumab As First-Line, Single-Drug Therapy for Patients With Unresectable Cutaneous Squamous Cell Carcinomas. [2021]

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

First-line avelumab in a cohort of 116 patients with metastatic Merkel cell carcinoma (JAVELIN Merkel 200): primary and biomarker analyses of a phase II study. [2022]

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

Immune checkpoint inhibitors to treat cutaneous malignancies. [2022]

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

Safety, Clinical Activity, and Biological Correlates of Response in Patients with Metastatic Melanoma: Results from a Phase I Trial of Atezolizumab. [2020]

7. England pubmed.ncbi.nlm.nih.gov

Five-year survival outcomes for patients with advanced melanoma treated with pembrolizumab in KEYNOTE-001. [2023]

8. England pubmed.ncbi.nlm.nih.gov

Real-world experience with pembrolizumab toxicities in advanced melanoma patients: a single-center experience in the UK. [2022]

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

Safety and clinical activity of atezolizumab in head and neck cancer: results from a phase I trial. [2022]

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

Immune Checkpoint Inhibitors for Treatment of Metastatic Melanoma of the Orbit and Ocular Adnexa. [2018]

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

Anti-PD1 Agents in the Treatment of Cutaneous Squamous Cell Carcinoma. [2023]

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

Incidence of Basal Cell Carcinoma and Squamous Cell Carcinoma in Patients on Antiprogrammed Cell Death-1 Therapy for Metastatic Melanoma. [2019]