Merkel Cell Carcinoma Clinical Trials (July 2026): 29 Recruiting Interventional Studies

Last updated: July 1, 2026

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Current Clinical Trial Landscape

About Merkel cell carcinoma (MCC):

MCC is a rare, aggressive neuroendocrine skin cancer. ~80% are associated with Merkel cell polyomavirus (MCPyV). It primarily affects older adults and immunocompromised patients. Highly responsive to immunotherapy.

Active research areas in July 2026:

Neoadjuvant checkpoint blockade for resectable Stage I-III disease — PD-1 alone and PD-1 + LAG-3 (nivolumab + relatlimab) combinations
Adding therapies to first-line PD-(L)1: IFx-Hu2.0 + pembrolizumab placebo-controlled Phase 2/3 in checkpoint-naive metastatic MCC
Anti-PD-(L)1 refractory strategies: ASTX727 (oral decitabine + cedazuridine) + retifanlimab (Zynyz, FDA-approved Mar 2023) after progression on anti-PD-(L)1
Peptide receptor radionuclide therapy (PRRT, Lu-177 dotatate) combined with immunotherapy — leverages MCC's neuroendocrine / somatostatin-receptor biology
DLL3 bispecific T-cell engagers (tarlatamab) combined with radiation in DLL3-expressing MCC
Tumor-infiltrating lymphocyte (TIL) cell therapy in MCC + cutaneous squamous cell carcinoma
Oncolytic virus platforms (MEM-288 IL-12 + anti-PD-L1) in MCC and other solid tumors
Immunotherapy protocols for kidney transplant recipients (sirolimus + prednisone backbone for graft-rejection mitigation)

Standard of care: Localized: surgery ± radiation. Metastatic: avelumab (Bavencio, FDA-approved 2017), pembrolizumab, or retifanlimab (Zynyz, FDA-approved March 2023 for metastatic MCC). MCC is highly immunogenic with ~50-60% response rates to first-line checkpoint inhibitors.

Recruiting Trials by Treatment Setting

Localized / Neoadjuvant (Resectable Stage I-III)

Before or alongside surgery for resectable disease — checkpoint blockade is increasingly delivered up front to shrink tumors and prime systemic immunity:

NCT05496036 - Neoadjuvant PD-1 blockade in resectable MCC (Phase 2)
NCT04975152 - Neoadjuvant cemiplimab in newly diagnosed or recurrent Stage I-II MCC (and locoregionally advanced cutaneous SCC), with biomarker analysis (Phase 1)
NCT06151236 - Neoadjuvant nivolumab + relatlimab (PD-1 + LAG-3) in Stage I-III resectable MCC (Phase 2) — first dedicated PD-1 + LAG-3 combination in resectable MCC
NCT07387198 - Neoadjuvant cemiplimab vs placebo in Stage I-II MCC (Phase 2 randomized, double-blind; not yet recruiting — check status before contacting)

Metastatic / Advanced (First-Line, Checkpoint-Inhibitor Naive)

For previously untreated metastatic disease — these are trials you can join before starting standard avelumab, pembrolizumab, or retifanlimab:

NCT06947928 - IFx-Hu2.0 + pembrolizumab vs placebo + pembrolizumab in checkpoint-inhibitor-naive advanced/metastatic MCC (Phase 2/3 placebo-controlled randomized — tests whether adding an intratumoral plasmid bacterial-antigen adjuvant boosts pembro response)
NCT05078047 - Standard vs every-3-month IO maintenance in patients responding after 6 months of standard IO (Phase 3)
NCT07302347 - KEYNOTE-G21 pembrolizumab in Japanese adult participants with advanced MCC (Phase 1/2 — geographic eligibility; mainly a Japan-based bridging study)

Relapsed / Refractory (After Anti-PD-(L)1 Progression)

After progression on or intolerance to checkpoint inhibitors — overcoming anti-PD-(L)1 resistance is the largest unmet need in MCC:

NCT07472322 - ASTX727 (oral decitabine + cedazuridine) + retifanlimab for advanced MCC after progression on anti-PD-(L)1 (Phase 1/2; epigenetic priming of immune response; not yet recruiting — check status)
NCT05583708 - Lu-177 dotatate (PRRT) + pembrolizumab for advanced MCC (Phase 2 iPRRT study; for SSTR-positive disease — ask about somatostatin-receptor PET imaging)
NCT06814496 - Tarlatamab (DLL3 bispecific T-cell engager) + radiation in DLL3-expressing tumors including MCC (Phase 1/2 RABBIT)
NCT07115043 - AZD6750 in select advanced solid tumors (Phase 1/2)

Cell Therapy — Tumor-Infiltrating Lymphocytes (TIL)

Cell therapy is emerging in MCC after the FDA approval of lifileucel TIL therapy in melanoma:

NCT07288073 - TIL therapy in MCC and cutaneous squamous cell carcinoma (Phase 2 feasibility study) — first dedicated TIL trial enrolling MCC patients

Special Populations

Trials addressing groups historically excluded from standard immunotherapy:

NCT05896839 - Nivolumab + ipilimumab + sirolimus + prednisone in kidney transplant recipients with unresectable/metastatic MCC or cutaneous melanoma (Phase 1/2 — sirolimus and prednisone are intended to mitigate graft rejection while permitting checkpoint blockade)

Trials by Treatment Approach

Checkpoint Inhibitors

PD-1 / PD-L1 inhibitors are the backbone of MCC treatment. Avelumab (Bavencio) was the first FDA-approved treatment for metastatic MCC (2017); pembrolizumab and retifanlimab (Zynyz, approved March 2023) followed. Combination trials (PD-1 + LAG-3, PD-1 + intratumoral adjuvants) and CPI-refractory strategies are the active frontiers. View all →

Oncolytic Virus Therapy

Oncolytic viruses can directly kill tumor cells and stimulate immune responses. MEM-288 is an engineered adenoviral platform expressing IL-12 designed to combine with anti-PD-(L)1.

NCT05076760 - MEM-288 oncolytic virus (IL-12 expressing) alone and combined with standard-of-care in advanced solid tumors including MCC (Phase 1)
View all oncolytic virus trials →

Combination Immunotherapy

Combinations of checkpoint inhibitors with other immunomodulators are being explored to deepen response and overcome resistance — nivolumab + relatlimab (PD-1 + LAG-3, NCT06151236 in neoadjuvant), nivolumab + ipilimumab in transplant recipients (NCT05896839), and IFx-Hu2.0 intratumoral plasmid added to pembrolizumab (NCT06947928).

Targeted Therapy & Novel Mechanisms

Novel targeted agents and epigenetic / chromatin-modifying combinations are being tested, mostly for patients who progress on immunotherapy.

NCT06021626 - CRD3874-SI in solid tumors including MCC (Phase 1)
NCT07472322 - ASTX727 (oral decitabine + cedazuridine, hypomethylating agent) + retifanlimab in CPI-refractory MCC (Phase 1/2)
NCT06814496 - Tarlatamab DLL3 bispecific T-cell engager + radiation (Phase 1/2 RABBIT)

Frequently Asked Questions

How do I find Merkel cell carcinoma clinical trials?

Paste your medical summary into ClinTrialFinder to get AI-matched Merkel cell cancer trials in minutes. The tool considers your disease stage, prior immunotherapy response, and MCPyV status.

What Merkel cell carcinoma trials are currently recruiting?

There are 29 recruiting interventional trials for Merkel cell carcinoma as of July 2026, including neoadjuvant PD-1 and PD-1 + LAG-3 combinations for resectable Stage I-III disease, first-line IFx-Hu2.0 + pembrolizumab (Phase 2/3, checkpoint-naive), ASTX727 + retifanlimab after anti-PD-(L)1 progression, PRRT (Lu-177 dotatate) + pembrolizumab, DLL3 bispecific T-cell engagers, TIL cell therapy, oncolytic virus therapy, and protocols for kidney transplant recipients.

What trials are available after my Merkel cell carcinoma progressed on avelumab or pembrolizumab?

Several trials specifically enroll patients after progression on anti-PD-(L)1, including ASTX727 (oral decitabine + cedazuridine) plus retifanlimab (NCT07472322, Phase 1/2), PRRT + pembrolizumab for SSTR-positive MCC (NCT05583708), tarlatamab DLL3 bispecific + radiation (NCT06814496), and TIL (tumor-infiltrating lymphocyte) cell therapy (NCT07288073). Ask your oncologist about somatostatin-receptor PET imaging and tumor sequencing to broaden your trial options.

Are there clinical trials for Stage I-III resectable Merkel cell carcinoma?

Yes. Several neoadjuvant trials enroll resectable MCC before surgery: neoadjuvant PD-1 blockade (NCT05496036, Phase 2), neoadjuvant cemiplimab for Stage I-II MCC (NCT04975152, Phase 1), and neoadjuvant nivolumab + relatlimab (PD-1 + LAG-3) for Stage I-III resectable MCC (NCT06151236, Phase 2). A randomized Phase 2 cemiplimab vs placebo trial (NCT07387198) is opening soon.

Are there Merkel cell carcinoma trials for kidney transplant recipients or other immunocompromised patients?

Yes. NCT05896839 (Phase 1/2) enrolls kidney transplant recipients with unresectable or metastatic MCC or melanoma on nivolumab + ipilimumab combined with sirolimus + prednisone — the steroid and mTOR-inhibitor backbone is designed to reduce graft rejection risk while still permitting checkpoint blockade. Most other MCC trials exclude solid-organ transplant recipients, so this is one of the few dedicated options.

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