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MelanomaPhase 2NCT06771544

Metronomic Cyclophosphamide With Pembrolizumab in Checkpoint Inhibitor Refractory Melanoma

A Phase 2 study testing Pembrolizumab and Cyclophosphamide in people with Melanoma and Melanoma Stage III, run by University of California, Irvine at 1 site in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial summary

This is a phase 2, single-arm, open label clinical trial determining efficacy of Cyclophosphamide and Pembrolizumab in subjects with melanoma. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Melanoma, Melanoma Stage III, Melanoma (Skin)
What is being tested?
Pembrolizumab and Cyclophosphamide
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
14 participants
Where
1 siteUnited States
Study dates
23 Dec 2024to Dec 2028
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Age ≥18 years at the time of signing informed consent form (ICF)
  • Patients must have unresectable Stage III or Stage IV non-ocular melanoma per American Joint Committee on Cancer 8th Edition Staging Criteria not amenable to local therapy
  • Participants must have measurable disease by RECIST v1.1 criteria as assessed by investigator/ radiology. Lesions situated in a previously irradiated area are considered measurable if progression has been shown in such lesions.
  • Participants must have Eastern Cooperative Group (ECOG) performance status score of 0, 1 or 2 at screening visit.
  • Life expectancy of at least 12 weeks
  • Adequate bone marrow, liver, and renal function
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  • Hemoglobin ≥9.0 g/dL
  • Platelets ≥100/mm3
  • ANC ≥1.5/mm3
  • Creatinine Clearance ≥ 30mL/min Cockcroft-Gault CrCl, mL/min = (140 - age) × (weight, kg) × (0.85 if female) / (72 × Cr, mg/dL).
  • AST and ALT less than 3 times the Upper Limit of Normal or less than 5 times the Upper Limit of normal with liver metastases. T Bilirubin < 3.1 mg/dL.
  • Has progressed on a prior PD-1/PD-L1 treatment
  • Recovered from toxicities of pembrolizumab to Grade ≤1, excluding endocrine toxicities
  • Prior Receipt of PD-1/PD-L1 therapy within 9 weeks prior to the first dose of the investigational therapy.
  • Women of childbearing potential must have had a negative pregnancy test performed within 7 days prior to the start of treatment
  • Females of childbearing potential and males must be willing and able to use an adequate method of contraception to avoid pregnancy for the duration of the study.
  • Male and female participants of childbearing potential who are sexually active with a non-sterilized partner must agree to use highly effective methods of birth control from the trial screening date until 3 months after the final dose of study intervention; cessation of birth control after this point shall be discussed with a responsible physician.
  • Pregnant or lactating women are prohibited from enrolling in this study.
  • Male participants are not allowed to donate sperm from the time of enrollment until 6 months after administration of study interventions.

Who cannot join

  • Participants with a diagnosis of ocular or metastatic uveal melanoma
  • Participants with a history of a malignant disease other than those being treated in this study. The following exceptions are permitted:
  • Malignancies that were treated curatively and have not recurred within 2 years. Shorter intervals can be considered after discussion with the Principal Investigator.
  • Completely resected basal cell and squamous cell skin cancers.
  • Any malignancy considered to be indolent and that has never required therapy, such as chronic lymphocytic leukemia.
  • Completely resected carcinoma in situ of any type
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  • Participants ineligible to be retreated with pembrolizumab due to a treatment-related AE while on a prior anti-PD(L)-1 regimen that led to discontinuation of that prior therapy and would thus prevent retreatment or with an immune-related adverse event (irAE) of grade 3 or greater
  • Participants with known untreated or symptomatic central nervous system (CNS) metastases and/or carcinomatous meningitis. NOTE: Participants with previously treated brain metastases may participate provided ALL of the following apply:
  • Treated CNS lesions are radiographically stable (without evidence of progression for ≥ 28 days prior to the first dose of study intervention) after intervention (eg, surgery and/or radiation).
  • Neurologically stable and on stable dose of ≤ 10mg of prednisone equivalent steroids for at least 7 days prior to the first dose of study intervention.
  • Any prior investigational or standard cancer therapy, with exception of PD-1/PD-L1 (includes nivolumab + Relatlimab) therapy, chemotherapy or radiation within 6-9 weeks of the first dose of the investigational therapy (see Inclusion Criteria)
  • Presence of B-RAF driver mutation without prior receipt of BRAF +/- MEK inhibitors, unless patient declines BRAF +/-MEK inhibition for any reason or is unable to tolerate BRAF and/or MEK inhibitors.
  • Participants with a known history of chronic viral infections as indicated below. If patients do not have a known history, testing is not required during the screening period to confirm the patient has an active infection.
  • Known HBV infection defined as hepatitis B surface antigen reactive. NOTE: Participants with HBV infection on stable anti-viral therapy for > 4 weeks prior to the planned first study intervention and viral load confirmed as undetectable during Screening may be eligible.
  • Known active HCV infection defined as detectable HCV RNA (qualitative) infection. NOTE: History of HCV is not exclusionary if participant has received curative treatment and viral load is confirmed as undetectable during Screening.
  • Active HIV infection. Those with HIV infections on combination antiretroviral medications with stable CD4 count >200/microliters as measured within screening time period. If the patient does not have a known history of HIV, then testing is not required during screening to confirm presence or absence of HIV.
  • Positive serum pregnancy test
  • Participants with out-of-range screening laboratory values as defined below. NOTE: Hematology evaluations must be performed >7 days from any blood transfusion. Or blood product transfusion or from any dose of hematologic growth factor.
  • Glomerular filtration rate (calculated using the Chronic Kidney Disease Epidemiology Collaboration formula) < 30 mL/min
  • Total bilirubin > 1.5 × ULN; participants with Gilbert's syndrome are excluded if total bilirubin > 3.0 × ULN; or direct bilirubin > 1.5 × ULN
  • Albumin < 3.0 g/dL
  • Absolute lymphocyte count < 0.5 × 10^9/L
  • Participants with a history of allogeneic tissue/solid organ transplant

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Chao Family Comprehensive Cancer Center University of California, Irvine contact

1-877-827-8839

ucstudy@uci.edu

University of California Irvine Medical contact

United States1 site, 1 recruiting

  • Chao Family Comprehensive Cancer Center University of California, Irvine

    Orange, California, 92868

    Warren Chow, MD, 877-827-8839, ucstudy@uci.edu

    Recruiting

Other trials in United States

About this study

This is a phase 2, single-arm, open label clinical trial determining efficacy of Cyclophosphamide and Pembrolizumab in subjects with melanoma.

Keywords
Melanoma, Melanoma, Stage III, Skin, Melanoma, Stage IV, Pembrolizumab, Cyclophosphamide
Medical subject headings
Melanoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT06771544
Study groupRoleWhat they receive
Pembrolizumab + CyclophosphamideExperimentalPembrolizumab 200mg IV every 21 days or 400 mg IV every 42 days Cyclophosphamide 50mg PO daily on days 1-14 every 21 days for melanoma patients
Receives: Drug: Pembrolizumab; Drug: Cyclophosphamide

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Objective Response Rate (ORR) by RECIST v1.1

    Sum of Complete Response (CR) and Partial Response (PR) by RECIST v 1.1. Per Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.1): Complete Response (CR) is defined as the disappearance of all target lesions; Partial Response (PR) is defined as a 30% decrease in the sum of diameters of target lesions. ORR = CR + PR

    Measured: Up to 3 years

  2. Number of Patients with Adverse Events

    Number of Patients who received at least one dose of Pembrolizumab with Cyclophosphamide with any reported Adverse Events (AEs) using the CTCAE version 5.0 for reporting of nonhematologic AEs and modified criteria for hematologic AEs.

    Measured: Up to 3 years

  3. Number of Patients with Immune Related Adverse Events

    Number of Patients who received at least one dose of Pembrolizumab with Cyclophosphamide with reported immune related AEs (irAEs) using the CTCAE version 5.0 for reporting of nonhematologic AEs and modified criteria for hematologic AEs.

    Measured: Up to 3 years

  4. Number of Patients who Discontinued Treatment Due to Reported Adverse Events

    Number of Patients who received at least one dose of Pembrolizumab with Cyclophosphamide requiring discontinuation of therapy due to reported AEs using the CTCAE version 5.0 for reporting of nonhematologic AEs and modified criteria for hematologic AEs..

    Measured: Up to 3 years

  5. Comparative Analysis of Immune Cells

    Mean, median, percentage and total counts of immune T cell subsets pre-treatment and after 2 three-week cycles of metronomic cyclophosphamide and pembrolizumab.

    Measured: Up to 3 years

Secondary outcomes (5)

  1. Objective Response Rate (ORR) by iRECIST

    Sum of Complete Response (CR) and Partial Response (PR) by Immunotherapy Response Evaluation Criteria in Solid Tumors (iRECIST). Per iRECIST: Immune Complete Response (iCR) is defined the complete disappearance of the tumor and non-tumor lesions; Immune Partial Response (iPR) is defined as a 30% tumor load decrease from baseline; Immune Stable Disease (iSD) is defined as when neither iCR nor iPR apply and there is no tumor progression; Unconfirmed Progressive Disease (iUPD) is defined as a 20% or greater increase in tumor burden or an appearance of a new target or non-target lesion; Confirmed Progressive Disease (iCPD) is defined as an increase of 5mm or greater in target tumor burden, or new target lesion, or any increase in non-target disease; Immune Best overall Response (IBOR) is defined as the best timepoint response recorded from the start to the end of the immunotherapy. ORR based on iRECIST refers to the percentage of patients in a clinical trial who experience a measurable

    Measured: Up to 3 years

  2. Clinical Benefit Rate

    Complete Response, Partial Response, and >6 months of stable disease as evaluated by RECIST v 1.1 and immune RECIST (iRECIST).

    Per Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.1): Complete Response (CR) is defined as the disappearance of all target lesions; Partial Response (PR) is defined as a 30% decrease in the sum of diameters of target lesions. Stable Disease is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum diameters while on study

    Measured: Up to 3 years

  3. Overall Survival

    Survival rate of subjects who received at least one dose of Pembrolizumab with Cyclophosphamide

    Measured: Up to 3 years

  4. Progression Free Survival

    Survival rate of subjects who received at least one dose of Pembrolizumab with Cyclophosphamide without Progression of their disease.

    Measured: Up to 3 years.

  5. Duration of Response

    Duration of Response of subjects who received at least one dose of Pembrolizumab with Cyclophosphamide

    Measured: Up to 3 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted13 Jan 2025
  2. Study start23 Dec 2024
  3. Primary completionDec 2027 (estimated)
  4. Study completionDec 2028 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
14 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06771544
Sponsor's protocol ID
6168
Other IDs
UCI 22-49
Status last verified
Mar 2026
First submitted
7 Jan 2025
Last updated
10 Mar 2026
Results posted
No
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Pembrolizumab and Cyclophosphamide in people with Melanoma and Melanoma Stage III, run by University of California, Irvine at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 19 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 10 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Chao Family Comprehensive Cancer Center University of California, Irvine (1-877-827-8839, ucstudy@uci.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Objective Response Rate (ORR) by RECIST v1.1 (time frame: Up to 3 years). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06771544.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Mar 2026.

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