Clinical Stage III Cutaneous Melanoma AJCC v8Phase 2NCT07576725
Low Dose, Reduced Frequency Nivolumab for the Treatment of Unresectable or Metastatic Cancer, AFFORD IO Trial
A Phase 2 study testing Biospecimen Collection, Computed Tomography and Magnetic Resonance Imaging in people with Clinical Stage III Cutaneous Melanoma AJCC v8 and Clinical Stage III Cutaneous Merkel Cell Carcinoma AJCC v8, run by Fred Hutchinson Cancer Center at 1 site in Uganda.
Trial summary
This phase II trial studies how well low dose, reduced frequency nivolumab works in treating patients with cancer that cannot be removed by surgery (unresectable) or that has spread from where it first started (primary site) to other places in the body (metastatic). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Clinical Stage III Cutaneous Melanoma AJCC v8, Clinical Stage III Cutaneous Merkel Cell Carcinoma AJCC v8, Clinical Stage IV Cutaneous Melanoma AJCC v8
- What is being tested?
- Biospecimen Collection, Computed Tomography and Magnetic Resonance Imaging
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 1 siteUganda
- Study dates
- 1 Dec 2026to 31 Aug 2029
- Phase
- Phase 2
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
- Participants are eligible if they have one of these histologically confirmed, unresectable or metastatic cancer types listed below, based upon historical responsiveness to anti-PD-(L)1 agents
- Non-small cell lung cancer (NSCLC) with documented PD-L1 expression (combined positive score [CPS] ≥ 1) (NOTE: Participants with known driver oncogenic mutations/rearrangements, including EGFR, ALK and ROS-1, will be excluded.)
- Head and neck squamous cell carcinoma (HNSCC) with documented PD-L1 expression (CPS ≥ 1)
- Clear cell renal cell carcinoma (ccRCC) (NOTE: Other subtypes may be permitted after approval by the Medical Monitor)
- Melanoma (cutaneous, acral-lentiginous and mucosal subtypes), and non-melanoma skin cancers, (cutaneous squamous cell carcinoma [CSCC], basal cell carcinoma [BCC] and Merkel cell carcinoma [MCC])
- Hodgkin's lymphoma
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- Urothelial carcinoma
- Cervical cancer with documented PD-L1 expression (CPS ≥ 1)
- Colorectal cancer with high microsatellite instability (MSI) or mismatch repair deficiency
- Kaposi sarcoma (KS) without clinical concern for multicentric Castleman's disease (MCD)
- Any cancer type with historical data suggesting an ORR > 20% with anti-PD(L)-1 agents (NOTE: All participants in this category must be approved by the Medical Monitor prior to enrollment.)
- Must have experienced disease progression after or deemed not to be a good candidate for available curative systemic therapy options
- Presence of at least one measurable tumor, per RECIST v1.1
- Age 18 or older. (NOTE: Both men and women, and members of all races and ethnic groups are eligible for this trial.)
- Eastern Cooperative Oncology Group (ECOG) performance score of 0-2
- Absolute neutrophil count (ANC) ≥ 1.0 × 10^9/L
- Platelet count ≥ 75 × 10^9/L
- Hemoglobin ≥ 9 g/dL (NOTE: Participants may have been transfused)
- Total bilirubin level ≤ 1.5 × the upper limit of normal (ULN) (or total bilirubin ≤ 2.5 × upper limit of normal [ULN] in participants with Gilbert's syndrome)
- Estimated creatinine clearance ≥ 30mL/min according to the Cockcroft-Gault formula or according to local institutional standard
- Must consent to undergo serial research blood draws at study defined timepoints, unless deemed unsafe or not feasible by the treating investigator
- Must have an ability to understand and provide consent to the institutional review board (IRB)-approved informed consent form (ICF) document(s)
- Women of childbearing potential must have a negative serum or urine pregnancy test at screening
- Both male and female participants must be willing to use highly effective contraception, as stipulated in national or local guidelines, throughout the study and for at least 180 days after the last treatment administration, if the risk of conception exists
Who cannot join
- Prior exposure to any immune-checkpoint inhibitor for any reason
- Residual adverse event(s) from prior therapy grade > 1 (National Cancer Institute [NCI]-Common Terminology Criteria for Adverse Events [CTCAE] v6.0) that could interfere with study endpoints or put participant safety at risk, as determined by the treating investigator
- Known active central nervous system (CNS) metastases and/or prior history of leptomeningeal cancer involvement
- Known history of another active malignancy (besides the eligible cancer diagnosis) within the last 3 years from day 1 of nivolumab that could interfere with study endpoints or put participant safety at risk. (NOTE: Exception will be made for adequately treated basal or squamous cell carcinoma of the skin or carcinoma in situ [skin, bladder, cervical, colorectal, breast] or low grade prostatic intraepithelial neoplasia or grade 1 prostate cancer. Any other neoplasm, which has been treated adequately and is adjudged by the treating investigator to have a low risk of progression during the study, could be enrolled only after approval from the medical monitor.)
- Known active hepatitis B virus (HBV) or hepatitis C virus (HCV), defined as follows:
- Active HBV is defined as a known positive hepatitis B virus surface antigen (HBsAg) result or positive total hepatitis B virus core antibody (anti-HBc) results in the absence of hepatitis B virus surface antibody (anti-HBsAb). (NOTE: When HBsAg is negative and HBcAb is positive, HBV-DNA should be measured. When HBV-deoxyribonucleic acid [DNA] is negative, this participant could be enrolled with close monitoring of HBV activities.)
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- Active hepatitis C virus (HCV) is defined as a known positive HCV antibody result and quantitative HCV-ribonucleic acid (RNA) results greater than the lower limits of detection of the assay. (NOTE: Participants who have had definitive treatment for HCV are permitted if HCV-RNA is undetectable.)
- Known uncontrolled HIV infection. (NOTE: HIV-infected participants may be allowed if all the following criteria are met: CD4 count ≥ 100/μL, viral load less than 200 copies/mL, and clinically stable on antiretroviral therapy [ART] for at least 3 months.)
- These participants will be enrolled only after approval from the medical monitor
- Known active autoimmune disease or an allograft requiring systemic immunosuppression with corticosteroids (> 10 mg/day of prednisone or equivalent) or immunosuppressive drugs within the past 2 years before the first dose of nivolumab. (NOTE: Exceptions will be made for participants with autoimmune conditions such as diabetes type I, vitiligo, psoriasis, hypothyroid or hyperthyroid diseases not requiring immunosuppressive treatment; participants receiving physiologic corticosteroid replacement therapy at doses < 10 mg/day of prednisone or equivalent for adrenal or pituitary insufficiency; participants with a condition such as asthma or chronic obstructive pulmonary disease that requires intermittent use of steroids or those who require brief courses of corticosteroids for prophylaxis [e.g., contrast dye allergy], nivolumab-related standard premedication, and/or treatment of non-serious immune related adverse events. Any other situation must be discussed with the medical monitor for risk/benefit assessment.)
- Immunosuppressed status due to severe uncontrolled diabetes, concurrent uncontrolled hematological malignancy, or other comorbidities
- Known history of serious, active infections (aside from well-controlled HIV, as per exclusion criterion #6) requiring systemic antimicrobial agents within 14 days before the first dose of nivolumab. (NOTE: Chronic infections such as herpes simplex virus requiring suppressive therapy may be allowed after discussion with the medical monitor for risk/benefit assessment.)
- Known history of clinically significant interstitial lung disease, or active noninfectious pneumonitis
- Clinically significant (i.e., active) cardiovascular disease such as cerebral vascular accident or myocardial infarction within 6 months prior to first dose of nivolumab, ongoing unstable angina or congestive heart failure (New York Heart Association Classification class II-IV), or serious cardiac arrhythmia that could jeopardize participant safety on the study
- Receipt of live vaccine(s) within 30 days of planned start of nivolumab. (NOTE: Examples of live vaccines include but are not limited to measles, mumps, rubella, varicella-zoster [chickenpox], yellow fever, rabies, bacillus Calmette Guerin [BCG], and typhoid vaccines. Seasonal influenza vaccines for injection are generally killed-virus vaccines and are allowed; however, intranasal influenza vaccines are live, attenuated vaccines and are not allowed.)
- Known severe acute or chronic medical conditions such as uncontrolled seizure disorder, serious psychiatric illness, or laboratory abnormalities, that may increase the risk associated with study participation or may interfere with the interpretation of study endpoints and, in the judgment of the treating investigator, would make the participant inappropriate for entry into this study
- Known active tuberculosis (TB). (NOTE: Participants with latent TB will be allowed, provided they are receiving tuberculosis preventive therapy, after approval of the medical monitor.)
- Known allergy or hypersensitivity to any component of the study drug formulation (including excipients and additives) that could interfere with study endpoints or put participant safety at risk
- Pregnant or breast-feeding woman
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Uganda1 site
Uganda Cancer Institute
Kampala, 3935
Jackson Orem, 0782 320543, jackson.orem@uci.or.ug
Jackson Orem
About this study
Official title: AFFORD IO: A Phase 2 Trial of Low Dose, Reduced Frequency Nivolumab (Anti-PD-1 Antibody) in Patients With Unresectable or Metastatic Cancer
This phase II trial studies how well low dose, reduced frequency nivolumab works in treating patients with cancer that cannot be removed by surgery (unresectable) or that has spread from where it first started (primary site) to other places in the body (metastatic). Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Nivolumab is a type of immune checkpoint inhibitor (ICI). ICIs have revolutionized the treatment of numerous cancers with remarkable improvement in participant outcomes. However, accessibility of ICIs is extremely poor on a global scale, mainly due to high costs. Previous research has suggested that these drugs can be given at lower doses and reduced frequency than their approved dosing regimens, with similar results. Giving nivolumab at a lower dose and less often may help reduce the cost of therapy, improve immunotherapy accessibility, and therefore improve survival outcomes globally.
Read the detailed description
OUTLINE:
INDUCTION PHASE: Patients receive nivolumab intravenously (IV) over approximately 30 minutes on days 1 and 45 in the absence of disease progression or unacceptable toxicity. Patients who are benefitting after 45 days proceed to Maintenance Phase.
MAINTENANCE PHASE: Patients receive nivolumab IV over approximately 30 minutes every 90 days (days 90, 180, 270 and 360) in the absence of disease progression or unacceptable toxicity.
All patients also undergo computed tomography (CT)/magnetic resonance imaging (MRI) and blood sample collection throughout the study. Patients may also undergo urine sample collection throughout the study.
After completion of study treatment, patients are followed up at 90 days and then every 12 months for up to 4 years.
- Conditions
- Clinical Stage III Cutaneous Melanoma AJCC v8, Clinical Stage III Cutaneous Merkel Cell Carcinoma AJCC v8, Clinical Stage IV Cutaneous Melanoma AJCC v8, Clinical Stage IV Cutaneous Merkel Cell Carcinoma AJCC v8, Hodgkin Lymphoma, Kaposi Sarcoma
- Being tested
- Biospecimen Collection, Computed Tomography, Magnetic Resonance Imaging, Nivolumab
- Medical subject headings
- Hodgkin Disease, Sarcoma, Kaposi, Carcinoma, Basal Cell, Uterine Cervical Neoplasms, Clear-cell metastatic renal cell carcinoma, Colorectal Neoplasms, Melanoma, Squamous Cell Carcinoma of Head and Neck
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Biospecimen CollectionProcedure or surgery
Also called Biological Sample Collection, Biospecimen Collected, Specimen Collection
Undergo collection of urine and/or blood samples
Computed TomographyProcedure or surgery
Also called CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography
Undergo CT
Magnetic Resonance ImagingProcedure or surgery
Also called Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan
Undergo MRI
NivolumabBiological
Also called ABP 206, BCD-263, BMS 936558, BMS-936558
Given IV
| Study group | Role | What they receive |
|---|---|---|
| Treatment (low dose, reduced frequency nivolumab) | Experimental | INDUCTION PHASE: Patients receive nivolumab IV over approximately 30 minutes on days 1 and 45 in the absence of disease progression or unacceptable toxicity. Patients who are benefitting after 45 days proceed to Maintenance Phase.
MAINTENANCE PHASE: Patients receive nivolumab IV over approximately 30 minutes every 90 days (days 90, 180, 270 and 360) in the absence of disease progression or unacceptable toxicity.
All patients also undergo CT/MRI and blood sample collection throughout the study. Patients may also undergo urine sample collection throughout the study. Receives: Procedure: Biospecimen Collection; Procedure: Computed Tomography; Procedure: Magnetic Resonance Imaging; Biological: Nivolumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective response
Defined as the best objective response of complete response (CR) or partial response (PR), as determined by investigator assessment per Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1.
Measured: Up to 4 years after completion of study treatment
Secondary outcomes (7)
Duration of response (DOR)
Will be assessed per RECIST 1.1. The Kaplan-Meier (KM) technique will be used to obtain estimates of DOR. For event-based survival analyses in participants without documentation of the event, survival will be censored on the last date the participant was known to be event free. The standard error of the KM estimates will be computed using the Greenwood formula (Kalbfleisch \& Prentice, 2002), and standard errors from the matrix form of Greenwood's formula for cumulative incidence estimates. Median time to event, if reached, will be presented with a 90% confidence interval based on the Brookmeyer and Crowley method (Kalbfleisch \& Prentice, 2002).
Measured: From the earliest date of disease response (CR or PR) until the earliest date of disease progression, or the date of death from any cause, assessed up to 4 years after completion of study treatment
Disease control
Defined as achievement of CR, PR, or stable disease as a patient's best objective response to the study treatment, per RECIST v1.1. For event-based survival analyses in participants without documentation of the event, survival will be censored on the last date the participant was known to be event free. The standard error of the KM estimates will be computed using the Greenwood formula (Kalbfleisch \& Prentice, 2002), and standard errors from the matrix form of Greenwood's formula for cumulative incidence estimates. Median time to event, if reached, will be presented with a 90% confidence interval based on the Brookmeyer and Crowley method (Kalbfleisch \& Prentice, 2002).
Measured: Up to 4 years after completion of study treatment
Progression free survival (PFS)
The KM technique will be used to obtain estimates of PFS. For event-based survival analyses in participants without documentation of the event, survival will be censored on the last date the participant was known to be event free. The standard error of the KM estimates will be computed using the Greenwood formula (Kalbfleisch \& Prentice, 2002), and standard errors from the matrix form of Greenwood's formula for cumulative incidence estimates. Median time to event, if reached, will be presented with a 90% confidence interval based on the Brookmeyer and Crowley method (Kalbfleisch \& Prentice, 2002).
Measured: From date of first dose of study treatment until the earliest date of disease progression, or the date of death from any cause, assessed up to 4 years after completion of study treatment
Overall survival (OS)
The KM technique will be used to obtain estimates of OS. For event-based survival analyses in participants without documentation of the event, survival will be censored on the last date the participant was known to be event free. The standard error of the KM estimates will be computed using the Greenwood formula (Kalbfleisch \& Prentice, 2002), and standard errors from the matrix form of Greenwood's formula for cumulative incidence estimates. Median time to event, if reached, will be presented with a 90% confidence interval based on the Brookmeyer and Crowley method (Kalbfleisch \& Prentice, 2002).
Measured: From date of first dose of study treatment until the date of death from any cause, assessed up to 4 years after completion of study treatment
Disease specific survival
For event-based survival analyses in participants without documentation of the event, survival will be censored on the last date the participant was known to be event free. The standard error of the KM estimates will be computed using the Greenwood formula (Kalbfleisch \& Prentice, 2002), and standard errors from the matrix form of Greenwood's formula for cumulative incidence estimates. Median time to event, if reached, will be presented with a 90% confidence interval based on the Brookmeyer and Crowley method (Kalbfleisch \& Prentice, 2002).
Measured: From date of first dose of study treatment until the date of death, assessed up to 4 years after completion of study treatment
Incidence of adverse events
Will include immune-related adverse events, treatment interruption and treatment discontinuation, and the use of immunosuppressive medications for toxicities.
Measured: Up to 90 days years after completion of study treatment
Accrual and by compliance with treatment timepoints
Feasibility defined by accrual and by compliance with treatment timepoints in this unique setting.
Measured: Up to 4 years after completion of study treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 May 2026
- Study start1 Dec 2026 (estimated)
- Primary completion31 Aug 2029 (estimated)
- Study completion31 Aug 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Clinical Stage III Cutaneous Melanoma AJCC v8Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Fred Hutchinson Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- The Wayne D. Kuni and Joan E. Kuni Foundation
- Responsible party
- Sponsor
- Investigators
- Shailender Bhatia, MD, Principal investigator, Fred Hutch/University of Washington Cancer Consortium
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07576725
- Sponsor's protocol ID
- RG1125119
- Other IDs
- NCI-2026-01874
- Status last verified
- May 2026
- First submitted
- 1 May 2026
- Last updated
- 17 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No