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

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether short-term fasting can reduce side effects or enhance the effectiveness of immunotherapy in patients with advanced or metastatic skin cancer. Participants will fast briefly before and after receiving a type of immunotherapy (PD-1/PD-L1 inhibitors) that aids the immune system in targeting and fighting cancer. The trial targets patients whose skin cancer has spread and who have undergone no more than two previous treatments. This trial may suit individuals with advanced skin cancer who have had no more than two systemic treatments and are open to fasting. As a Phase 1 trial, the research aims to understand how the treatment works in people, offering participants a chance to be among the first to explore this innovative approach.

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.

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

Research has shown that short-term fasting might enhance the safety of treatments with PD-1 and PD-L1 inhibitors, a type of cancer therapy. In one study, mice on a fasting-mimicking diet experienced fewer side effects, such as heart problems, while combating cancer. Another review suggested that fasting could boost the immune system's ability to fight tumors, potentially increasing treatment effectiveness.

PD-1/PD-L1 inhibitors have already received approval for some cancers, indicating general safety. However, as this trial is in an early stage, researchers are closely monitoring safety and side effects. So far, these treatments are usually well-tolerated, though some side effects like tiredness or inflammation may occur.

Overall, fasting might help reduce side effects and enhance the effectiveness of these cancer treatments. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about combining fasting with PD-1/PD-L1 inhibitors for skin cancer because this approach could enhance the effectiveness of existing immunotherapies like pembrolizumab and nivolumab. Unlike standard therapies, which focus solely on the immune checkpoint inhibitors, this method integrates short-term fasting (STF), which may boost the body's immune response against cancer cells. The fasting component is believed to make cancer cells more vulnerable to treatment while potentially reducing side effects. This innovative combination aims to improve patient outcomes by making immunotherapy more potent and tolerable.

What evidence suggests that this trial's treatments could be effective for skin cancer?

Research has shown that short-term fasting might enhance the effectiveness of cancer treatments. It can boost the immune system's ability to fight cancer and may make cancer cells more susceptible to treatment. In this trial, participants will undergo short-term fasting combined with one of several PD-1/PD-L1 inhibitors, such as atezolizumab, pembrolizumab, or nivolumab. These monoclonal antibodies have demonstrated positive results for skin cancer. Specifically, atezolizumab has helped 24% of melanoma patients respond to treatment, while pembrolizumab has been linked to a 41% survival rate after three years in advanced melanoma cases. Nivolumab has shown a five-year survival rate of 44% for advanced melanoma. Other drugs like avelumab and cemiplimab also show promise, with strong response rates, indicating effectiveness in treating advanced skin cancers. Overall, combining these treatments with short-term fasting might enhance their effectiveness. ^{6 7 8 9 10}

Who Is on the Research Team?

Gino K. In

Principal Investigator

University of Southern California

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

Group I: Treatment (STF, PD-1/PD-L1 inhibitor) Experimental Treatment 12 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, dostarlimab IV over 30 minutes, retifanlimab IV over 30 minutes, toripalimab IV over 60 minutes, 30 minutes for subsequent dose, tislelizumab IV over 60 minutes for 1st dose, 30 minutes for subsequent doses, 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+

Published Research Related to This Trial

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 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]

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]

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]

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 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]

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]

Citations

1.

tecentriq-hcp.com

tecentriq-hcp.com/melanoma/efficacy/clinical-trial-results.html

IMspire150 efficacy results - TECENTRIQ-HCP.com

Learn more about efficacy outcomes in the IMspire150 clinical trial of TECENTRIQ® (atezolizumab) for first line BRAF V600+ Melanoma.

2.

clinicaltrials.gov

clinicaltrials.gov/study/NCT03901573?tab=results

High-Risk Skin Cancers With Atezolizumab Plus NT-I7

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are ...

3.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/31358540/

Results from a Phase I Trial of Atezolizumab

Conclusions: Atezolizumab was well tolerated, with durable responses and survival in patients with melanoma. PD-L1 expression, TMB, and Teff ...

4.

drugs.com

drugs.com/medical-answers/effective-atezolizumab-tecentriq-3552927/

How effective is atezolizumab (Tecentriq)?

Results showed that treatment with Tecentriq produced an overall response rate (ORR) of 24%. Of the 12 patients who achieved an objective ...

5.

tecentriq.com

tecentriq.com/hybreza/results/how-tecentriq-hybreza-may-help.html

Effectiveness & Safety of TECENTRIQ HYBREZA™ ...

TECENTRIQ HYBREZA injections was observed to be similarly effective in fighting cancer as TECENTRIQ infusions. In another study, most people preferred TECENTRIQ ...

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC10491752/

Fasting mimicking diet in mice delays cancer growth and ...

These results indicate that FMD cycles in combination with immunotherapy can delay cancer growth while reducing side effects including cardiotoxicity.

7.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC8946179/

Short-Term Fasting Synergizes with Solid Cancer Therapy by ...

This review summarizes preclinical and clinical evidence of fasting diets synergizing with cancer therapy by boosting antitumor immunity.

8.

cancer.gov

cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2020-01590

Short-term Fasting prior to Standard of Care PD-1/PD-L1 ...

This phase I trial studies the side effects of short-term fasting in patients with skin malignancy that has spread to other places in the body.

9.

withpower.com

withpower.com/trial/phase-1-skin-neoplasms-7-2020-bbb9c

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

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 ...

10.

clinicaltrials.gov

clinicaltrials.gov/study/NCT06438588

Study Details | NCT06438588 | Fasting Mimicking Diet for ...

Effect of Fasting Mimicking Diet (FMD) on Immune Related Adverse Events for Cancer Patients on Immune Checkpoint Inhibitors: The FMD-ICI Feasibility Pilot Study.