What Is Retifanlimab?
Retifanlimab is an investigational drug classified as a programmed death receptor-1 (PD-1)-blocking monoclonal antibody. This type of immunotherapy works by targeting the PD-1 protein on immune cells, which helps to release the brakes on the immune system. By blocking PD-1, retifanlimab aims to enhance the body's natural ability to recognize and fight cancer cells, allowing them to attack and destroy cancer cells more effectively.
This drug is currently under extensive investigation in a broad clinical development program. A total of 56 trials have been initiated for retifanlimab since its first trial began in 2015, with the latest trial starting in 2026. These studies have enrolled 4,843 participants to date, with 16 trials currently recruiting new patients. Retifanlimab is being studied for its potential to treat various types of cancer, including advanced solid tumors, breast cancer, Merkel cell carcinoma, and head and neck cancer. It is often investigated both as a standalone treatment and in combination with other therapies, such as chemotherapy, radiation, or other targeted drugs, to explore its full therapeutic potential.
Uses and Conditions Under Study
Retifanlimab is being investigated for its potential to treat a variety of cancers, primarily focusing on solid tumors. As a PD-1 blocking antibody, it is thought to help the immune system identify and attack cancer cells in these conditions.
- Advanced and Metastatic Solid Tumors: Retifanlimab is being studied in 9 trials for advanced or metastatic solid tumors and malignancies. These studies aim to determine its effectiveness in cancers that have spread or are difficult to treat with standard therapies.
- Breast Cancer: There are 6 trials investigating retifanlimab for breast cancer and breast neoplasms. One study explores its use in combination with the SV-BR-1-GM regimen for patients with metastatic or locally recurrent breast cancer who have failed standard therapy.
- Merkel Cell Carcinoma: This rare and aggressive skin cancer is the focus of 4 trials involving retifanlimab. Studies are exploring its use both alone and in combination with other agents, sometimes followed by surgery.
- Head and Neck Cancer: Retifanlimab is being evaluated in 3 trials for head and neck cancer. These studies often combine it with other treatments, such as chemotherapy, to improve outcomes.
- Glioma: This type of brain tumor is being studied in 2 trials with retifanlimab. Some trials investigate its use with radiation therapy and temozolomide.
- Pancreatic Adenocarcinoma: Retifanlimab is being explored in 2 trials for pancreatic adenocarcinoma, a challenging cancer to treat. Combinations with chemotherapy are being studied.
- Urothelial Carcinoma: This cancer, often found in the bladder, is also the subject of 2 trials with retifanlimab.
Dosing
Retifanlimab is administered intravenously (through a vein), typically as an infusion. The specific dose and frequency of administration are investigational and vary depending on the cancer type being studied and whether it is given alone or in combination with other treatments.
In various clinical trials, retifanlimab has been studied at a dose of 500 mg. This dose has been investigated for conditions such as melanoma, non-small cell lung cancer (NSCLC), urothelial carcinoma (UC), and renal cell carcinoma (RCC). Administration schedules have included dosing every two weeks (Q2W), every three weeks (Q3W), or every four weeks (Q4W), often as part of dose escalation or expansion cohorts to determine optimal regimens.
Retifanlimab is also frequently studied as part of combination therapies. For example, it has been combined with oral ASTX727, various chemotherapies, radiation therapy, and other investigational agents like ruxolitinib, axatilimab, or pemigatinib. These combination regimens involve complex dosing schedules tailored to the specific treatment protocol. The information on dosing reflects investigational use in adult participants within clinical trials.
Side Effects
In clinical trials involving Retifanlimab, side effects were monitored across 1556 patients receiving the drug compared to those on placebo. The most commonly reported side effect was anemia, affecting 58.3% of patients on Retifanlimab, compared to 62.3% of patients on placebo.
Other common side effects reported by patients taking Retifanlimab included:
- Nausea: 30.0% of patients on Retifanlimab experienced nausea, compared to 38.6% on placebo.
- Alopecia (hair loss): 25.1% of patients on Retifanlimab experienced alopecia, compared to 33.0% on placebo.
- Neutropenia (low white blood cell count): 23.3% of patients on Retifanlimab experienced neutropenia, compared to 28.4% on placebo.
- Diarrhea: 21.4% of patients on Retifanlimab experienced diarrhea, compared to 21.9% on placebo.
- Fatigue: 21.2% of patients on Retifanlimab experienced fatigue, compared to 24.6% on placebo.
- Decreased appetite: 21.1% of patients on Retifanlimab experienced decreased appetite, compared to 18.7% on placebo.
- Constipation: 20.3% of patients on Retifanlimab experienced constipation, compared to 24.0% on placebo.
Some laboratory abnormalities were also observed, such as a decrease in neutrophil count (20.6% on Retifanlimab vs 19.6% on placebo), a decrease in white blood cell count (16.2% on Retifanlimab vs 16.1% on placebo), and increased alanine aminotransferase (15.4% on Retifanlimab vs 15.2% on placebo).
Clinical Trial Results
Clinical trials have evaluated Retifanlimab in various cancer types, both as a standalone treatment and in combination with other therapies.
Metastatic Merkel Cell Carcinoma
In a study (NCT03599713) involving patients with metastatic Merkel cell carcinoma who had not previously received chemotherapy, Retifanlimab demonstrated meaningful responses. The objective response rate (ORR), meaning the percentage of patients whose cancer significantly shrank or disappeared, was 52.3%. The disease control rate (DCR), which includes patients with a complete response, partial response, or stable disease, was 60.4%. Patients in this group experienced a median progression-free survival (PFS) of 16.03 months, meaning half of the patients lived at least this long without their cancer worsening.
Squamous Carcinoma of the Anal Canal
For patients with squamous carcinoma of the anal canal who had progressed after platinum-based chemotherapy, a study (NCT03597295) investigated Retifanlimab. The objective response rate (ORR) was 13.8%, with a disease control rate (DCR) of 48.9%. Among those who responded, the median duration of response (DOR) was 9.5 months. The median overall survival (OS) for these patients was 13.4 months, and the median progression-free survival (PFS) was 2.3 months.
Recurrent Gliomas
A study (NCT03532295) explored Retifanlimab in combination with radiation therapy (RT) and bevacizumab for patients with recurrent gliomas. Two regimens were studied:
- Regimen A: Retifanlimab + RT + bevacizumab
- Regimen B: Retifanlimab + RT + bevacizumab + epacadostat
For Regimen A, 50% of participants were estimated to be alive at 12 months, with a median overall survival of 11.53 months. The progression-free survival at 12 months was 25%, with a median PFS of 6.98 months.
For Regimen B, 38% of participants were estimated to be alive at 12 months, with a median overall survival of 10.55 months. The progression-free survival at 12 months was 4%, with a median PFS of 7.20 months.
Immunogenicity
In a safety study (NCT02475213) evaluating enoblituzumab in combination with either pembrolizumab or Retifanlimab, 11 participants in one cohort (Cohort 4) developed anti-drug antibodies (ADA) to Retifanlimab.
Currently Recruiting Trials
Retifanlimab is currently being investigated in a variety of clinical trials, exploring its potential as a treatment for numerous types of cancer. These studies are designed to understand how Retifanlimab works, often in combination with other therapies, to improve outcomes for patients.
- A Phase 1/2 study, NCT07219576, is recruiting 40 participants with non-small cell lung carcinoma or renal cell carcinoma. Sponsored by the University of California, San Diego, this trial aims to determine the maximum safe dose of ruxolitinib when combined with Retifanlimab.
- For patients with advanced pancreatic adenocarcinoma, a Phase 1 study (NCT06896188) is evaluating Retifanlimab in combination with 9-ING-41 and mFOLFIRINOX chemotherapy. This trial, targeting 12 participants, focuses on safety for those without prior systemic therapy for advanced disease.
- M.D. Anderson Cancer Center is sponsoring a Phase 1 study (NCT06959537) for metastatic triple negative breast cancer (TNBC), enrolling 24 patients. The study seeks to find the optimal dose of cyclophosphamide and axatilimab when given alongside Retifanlimab.
- The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins is conducting an Early Phase 1 trial (NCT06610682) for 24 patients with BRAF-altered glioma. This study assesses plixorafenib alone or combined with Retifanlimab, evaluating safety and changes in ctDNA from plasma and CSF.
- In recurrent glioblastoma, a Phase 2 trial (NCT06160206) is recruiting 134 participants to compare Retifanlimab with bevacizumab and hypofractionated radiotherapy against bevacizumab and radiotherapy alone.
- A Phase 2 open-label study (NCT06389799) from Lund University Hospital is investigating pemigatinib and Retifanlimab in 33 patients with advanced dedifferentiated liposarcoma, an aggressive soft tissue sarcoma.
- The OHSU Knight Cancer Institute is running a Phase 1/2 trial (NCT06320405) for 38 patients with advanced or metastatic solid tumors, testing the safety and effectiveness of axatilimab in combination with Retifanlimab and paclitaxel.
- For metastatic colorectal cancer, the National Cancer Institute (NCI) is sponsoring a Phase 1/2 study (NCT06149481) for 60 participants, exploring a combination immunotherapy regimen including Retifanlimab.
- Incyte Corporation's Phase 1 study (NCT06179160) is enrolling 710 participants with advanced or metastatic solid tumors with KRAS G12D mutation, to determine the safety and tolerability of INCB161734, potentially in combination with other anticancer therapies like Retifanlimab.
- A large Phase 3 study (NCT06072612) is underway for 404 patients with advanced metastatic breast cancer, comparing the Bria-IMT regimen plus Retifanlimab against physician's choice of treatment.
- The University of Washington is conducting a Phase 1/2 trial (NCT05455697) for diffuse large B-cell lymphoma and related conditions, enrolling 35 patients to evaluate the safety of tafasitamab, Retifanlimab, and rituximab (TRR) with standard therapy.
- For recurrent IDH-mutant glioma, a Phase 2 study (NCT05345002) is recruiting 55 participants to assess the safety and immune response of All-Trans Retinoic Acid (ATRA) combined with Retifanlimab.
- A Phase 1 study (NCT05083754) from Johns Hopkins is investigating carmustine wafers with Retifanlimab and radiation, with or without temozolomide, in 50 newly diagnosed glioblastoma multiforme patients.
- Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) is sponsoring a Phase 2 trial (NCT05177133) for 25 patients with dMMR esophagogastric cancer, combining Retifanlimab with capecitabine and oxaliplatin.
- Memorial Sloan Kettering Cancer Center's Phase 1/2 study (NCT04577014) is enrolling 98 patients with advanced soft tissue sarcoma to determine the safety and effectiveness of Retifanlimab with gemcitabine and docetaxel.
- Finally, a Phase 2 sub-study (NCT04374305) is open for 109 participants with NF2-related schwannomatosis and progressive tumors, testing Retifanlimab plus bevacizumab among other experimental therapies.
Where to Participate
Clinical trials for Retifanlimab are widely accessible across the United States, with a broad geographic reach to ensure diverse participation. There are currently 110 study sites located in 77 cities across 26 states. Some of the cities with the most active recruiting sites include:
- Los Angeles, California (7 sites)
- New York, New York (6 sites)
- Baltimore, Maryland (4 sites)
- Santa Monica, California (4 sites)
- Jacksonville, Florida (3 sites)
- Port Jefferson Station, New York (3 sites)
- San Antonio, Texas (3 sites)
- Rochester, Minnesota (3 sites)
- Miami, Florida (3 sites)
- Philadelphia, Pennsylvania (2 sites)
Eligibility for these trials generally includes individuals aged 12 to 120 years, of all genders. Importantly, these studies are not open to healthy volunteers, as they focus on patients with specific medical conditions.
Development Timeline
The journey of Retifanlimab began with its first clinical trial on March 19, 2015, marking the start of its development as a potential new therapy. Since then, a robust clinical program has unfolded, with the latest trial initiated on March 16, 2026. To date, a total of 56 clinical trials have been conducted or are ongoing, involving approximately 4,843 participants.
Initial development focused on various advanced solid tumors, and the pipeline quickly expanded to include a wide array of cancers. Key sponsors like Incyte Corporation have driven much of this research, alongside academic institutions and other pharmaceutical companies. Retifanlimab's development has progressed through all phases of clinical research, with the majority of studies in Phase 2 (22 trials) and Phase 1 (16 trials), demonstrating a continuous effort to explore its safety and effectiveness in different settings. The drug's investigation has expanded to target specific conditions such as metastatic breast cancer, glioblastoma, pancreatic adenocarcinoma, and various sarcomas, reflecting a strategic expansion to address diverse unmet medical needs in oncology.