Summary of the 20th Annual MCC Multi-Center Interest Group (MMIG)

Summary of 20th Annual MMIG Meeting 

(Merkel cell carcinoma Multi-Center Interest Group) 

Friday, March 27th, 2026

Denver, CO & Virtual event 

Prepared by: Kate Biese, Brooke Chen, Myna Kommareddy, Krista Lachance, Paul Nghiem, & Ava Watson 

Announcements 

1. If you would like to view the meeting recording, please contact Kate directly ([email protected])
2. Please contact Paul Nghiem ([email protected]) or Kate Biese ([email protected]) if you would like to present at next year’s meeting or if you have any feedback to improve future meetings 

MMIG Meeting Agenda (times in MST)   

Meeting notes:

1. MCC Clinical Trial Updates

Nicki Bouché, BS & Victoria Wilk, BA (University of Washington)

• Patients can understand current research and explore personalized care plans on https://clinicaltrials.gov/
  • Includes MCC or other cancer specialized clinical trials
• Tarlatamab:
  • Redirects patient’s own immune system to target MCC
  • 90% MCC tumors are positive for DLL3 tumor- good target
  • 2 toxicities:
    • cytokine release syndrome
    • immune effector cell-associated neurotoxicity syndrome (ICANS)
  • Logistical challenges- delivered inpatient and hospitalizations required for 24 hours after first and second doses
  • Two trials: build foundation and expand tarlatamab in MCC treatment as next step
    • RABBIT Trial, Phase I study: concurrent tarlatamab with palliative and consolidative RT regimens
      • Currently in Arizona, Seattle soon
    • Monotherapy trial, phase II study: inclusive of MCC
      • 5 sites in CA
    • Overall: promising, but toxicity and logistical challenges need to be considered
  • Peluntamig (PT217)
    • Target DLL3 and CD47
    • SKYBRIDGE study:
      • Evaluate PT217 as monotherapy concurrent with chemotherapy
      • Recruiting in multiple states- very accessible
    • Intra-tumoral treatments: T-VEC, RP1, IFx-2.0
      • T-VEC is FDA approved for melanoma: used to treat localized injectable MCC tumors
      • RP1: similar oncolytic virus therapy to T-VEC with additional fusion protein to enhance cancer cell adhesion
        • Clinical trials with RP1 faced FDA regulatory challenges
        • IGNITE trial still showed strong clinical benefit- will work with FDA to design upcoming trials
      • IFx-2.0: TuHURA Trial
        • Phase III trial: IFx2.0 as adjunct to pembrolizumab in injectable lesions
        • Two arms: placebo +pembrolizumab vs IFx-2.0 +pembrolizumab
        • First-line only, aiming to enroll 118 participants across 25 sites
        • IFx-2.0 is injected intradermally using plasma DNA delivery system to express EMM55 to promote systemic anti-tumor response
      • Tumor Infiltrating Lymphocytes (TIL) Therapy
        • Phase II study: TIL cellular therapy (LN-145) and chemotherapy (fludarabine and cyclophosphamide) concurrent with IL-2 (Interleukin-2)
        • LN-145 (lifileucel) is FDA approved for melanoma treatment- will this work in MCC?
        • Located in Dana Farber Cancer Institute, Boston, MA
      • ADC Match
        • Phase II across 27 locations sponsored by National Cancer Institute
        • Patient given one of three antibody-drug conjugates based on pathology results:
          • Sacituzumab govitecan (Trop-2)
          • Enfortumab vedotin (Nectin-4)
          • Trastuzumab deruxtecan (HER2)
        • Delivers treatment directly to tumor cells- increase efficacy while decreasing toxicity?
      • Questions? Email [email protected]

2. Post-PD1 Therapies for Refractory MCC 

Tarek Haykal, MD (University of Michigan)

• Introduction to MCC:
  • Rare and aggressive skin cancer with neuroendocrine features that rapidly grows
  • 3000 cases diagnosed each year in US of which 40% are recurrences, when MCC recurs it comes with risk of morbidity and mortality, especially if locally advanced or metastatic
• Background in metastatic MCC:
  • Distant metastases arise within first 3 years
  • Historically, Overall survival at 5 years is 54%, but drops to 15% with metastatic disease
  • Historically treated with chemotherapy agents with short responses- not based on strong evidence; current treatment differs
• First line- metastatic MCC
  • Avelumab (PD-L1), Pembrolizumab (PD-1), Nivolumab (PD-1), Retifanlimab-dlwr (PD-1) with more promising ORR of 40-56%, longer response time, and all FDA approved for metastatic MCC
• Beyond First Line- Metastatic MCC
  • Two trials evaluated nivolumab/ipilimumab concurrent treatment, both with slightly lower (1mg/kg every 6 weeks) dose of ipilimumab compared to melanoma treatment
    • Checkmate-358: Nivolumab with and without Ipilimumab with recurrent or metastatic MCC- no big differences in ORR and survival rates between two groups
    • Kim at al. Lancet: combined nivolumab and ipilimumab with or without stereotactic body RT for advanced MCC, comparing ICI naïve and previous ICI- optimistic ORR for ICI naïve, and RT does not provide significant impact
    • Not a preferred first line option for MCC– limited benefit compared to PD-1 alone, and limited data in first line for ICI-naïve
    • MA aggregate response rate of 32%, but small data cohort
    • Experts recommend ipilimumab/nivolumab only after exposure to PD-1 first
  • Chemotherapy can be effective second or third line, especially if quick response needed or ICI is prohibitive due to high grade toxicities
    • Carboplatin/Etoposide preferred for chemotherapy
  • Other options:
    • Octreotide long actin release- if somatostatin receptor testing (+), then use somatostatin analog therapy. Based on retrospective data.
    • Pazopanib (TKI)-lower responses based on small dataset
    • T-VEC (Intralesional Talimogene Laherparepvec) for palliation of injectable sites of disease- used for melanoma
  • Consider clinical trials for first, second, and beyond lines in MCC
  • Limited data for other commercially available systemic or local therapies
  • Overall summary: PD-1/PD-L1 are well established for first line systemic options. Ipilimumab /nivolumab is not preferred for first line, though this or chemotherapy (carboplatin/etoposide) can be considered for second lines or beyond. Consider enrollment in clinical trials for determining treatment.
• Questions? Email [email protected] or @TarekHaykal1 on X

3. Adjuvant RT After Complete MCC Excision 

Dan Coit, MD (Memorial Sloan Kettering Cancer Center)

• Use of radiation after complete excision of primary MCC may be unnecessary
• 6 key factors in considering any adjuvant therapy
  • What is the absolute risk of local recurrence?
  • What is the absolute risk reduction of radiation?
  • What is the cost of radiation?
  • How effective is rescue therapy?
  • What are the patient biases?
  • What are the physician biases?
• Problem with existing evidence
  • A 2006 multicenter study showed that patients treated with surgery alone have a local recurrence rate of 40% at 5 years
  • Limitations
    • Few patients per center
    • Poorly defined methods
  • These and other flawed administrative database studies shape NCCN guidelines to recommend adjuvant RT for pts with clear margins and one or more risk factor
  • Risk factors for local recurrence have been extrapolated from risk factors for developing MCC and systemic progression of MCC, without evidence
• Challenges to understanding risk of local recurrence in MCC
  • Multicenter databases lack detailed data including
    • Margin size
    • Timing of recurrence
    • Disease-specific survival
  • Many single center databases are hampered by small sample size and incomplete follow-up
  • Sparse data exist for effectiveness of salvage therapy for locally recurrent MCC
• New study (large prospective single-center cohort)
  • Objective:
    • Describe incidence of local recurrence in patients who had margin-negative excision
    • Evaluate efficacy of salvage treatment
    • Identify risk factors for local recurrence
  • Findings
    • 447 pts with margin-negative excision; 393 patients treated with excision only, without adjuvant RT.
    • Cumulative incidence of local recurrence: 1.6%
    • Recurrence details:
      • 8 surgery only pts had local recurrence,
        • 2 recurred with local + systemic disease within 6 months, likely due to aggressive biology
        • 6 with local recurrence only, all of whom were effectively salvaged with further therapy
      • No risk factor significantly associated with increased risk of local recurrence
    • Takeaways
      • Local recurrence risk low (~2%)
      • >98% of pts cannot benefit from adjuvant radiation
      • Salvage therapy is uniformly effective for local recurrence
    • Conclusion: These data do not support routine use of adjuvant RT after complete excision of primary MCC

4. The Adjuvant MCC Radiation Conundrum: A Different Way to View the Debate?

Paul Nghiem, MD/PhD (University of Washington)

• Key issues
  • How do we balance risk of local recurrence with potential overtreatment with RT?
  • Difficult to predict who will benefit from RT
• Comparison of local recurrence rates
  • Kavanaugh et al. 2025 claims local recurrence rate after surgery only is ~2%
  • Issues
    • >10% received RT in this cohort, none of which experienced a local recurrence
    • These were higher risk pts (large tumor, LVI, etc)
  • 2% recurrence rate likely underestimates actual risk
• Seattle cohort data
  • Stage I-II pts (n = 291)
  • Comparing surgery only (n=96) vs. surgery + RT (n=195)
    • Surgery + RT pts have higher risk factors compared to surgery only
    • Findings
      • 15% of surgery only pts had a local first recurrence, 2.1% distant first recurrence
      • 1% of surgery + RT pts had a local first recurrence, 11% distant first recurrence
    • Data suggests surgery + RT pts have more aggressive MCC
  • Takeaway
    • Seattle cohort data shows 15% local recurrence rate for surgery only pts
    • Difficult to predict who will recur, ongoing analysis based on NCCN risk factors

5. Single Fraction 8Gy for Adjuvant Treatment of Low-Risk Merkel cell carcinoma: A Prospective Trial

Peter Ch’en, MPH (University of Washington) & Lisa Zaba, MD/PhD (Stanford University)

• Why Single Fraction 8 Gray Radiotherapy (SFRT)?
  • Adjuvant RT helpful in controlling microscopic residual disease after surgery, reduces local recurrence rates
  • Avoid excessive surgical margins with this approach
  • Convenience (~1 vs ~25 treatments)
  • SFRT has less side effects compared to conventional RT (cPORT)
• Seattle patient cohort
  • Stage I-II MCC
  • Observation (n = 111), cPORT (n = 156), SFRT (n = 43)
  • 88% of SFRT pts had ≤1 cm surgical margins
  • 77% of SFRT pts had head & neck primary
  • Patients receiving radiation have higher average number of risk factors compared to observation group
    • Observation (n = 111)
      • Mean RF: 1.2 ± 0.8
      • Median follow-up: 6.7 yrs
      • 15/111 = 14% local recurrence
    • cPORT (n = 156)
      • Mean RF: 1.6 ± 0.9
      • Median follow-up: 8.7 yrs
      • 4/156 = 3% local recurrence
    • SFRT (n = 43)
      • Mean RF: 1.6 ± 0.9
      • Median follow-up: 3.3 yrs
      • 0 local recurrences
    • SFRT adverse effect profile
      • 81% had no side effects
      • All had ≤ Grade 1 AEs
    • Call for Collaborators
      • Need for prospective multi-institutional trial to analyze adjuvant SFRT
      • Goal is to minimize patient morbidity and optimize outcomes
        • Proposed trial design
          • Enroll stage I-II pts (low-risk, s/p surgical excision)
          • Prospective Observation vs 8Gy adjuvant SFRT

6. Plans for a Study Using ctDNA as a Guide for Initiating Immunotherapy: TOMMORoW Trial

Tomoko Akaike, MD (University of Washington)

• Published Data
  • JCO cohort: Circulating Tumor DNA Assay Detects Merkel Cell Carcinoma Recurrence, Disease Progression, and Minimal Residual Disease: Surveillance and Prognostic Implications, published August 2024
    • 319 patients from 6 centers in US
    • ctDNA has high sensitivity (94-95%) and specificity (86-90%) for detecting clinically evident MCC
    • Works well for VP- and VN-MCC
    • Detects recurrence early
    • Broad adoption:
      • Per 2025 NCCN guidelines: reliable surveillance tool
      • Easy access: local clinic or at patient’s home
    • 2nd analysis of JCO cohort: Circulating tumor DNA level is associated with time to clinical recurrence in Merkel cell carcinoma: Implications for patient management, published in JAAD November 2025
      • Evaluate timing and prognostic significance of ctDNA levels relative to clinical recurrence
      • Overall, 52% of patients developed clinically evident disease (CED) within 6 months, and 77% within 12 months, after the first positive ctDNA. Patients with higher ctDNA levels tended to experience CED sooner.
      • Current dilemma: telling patients to ‘just wait’ until developing CED with positive ctDNA and negative scans, is it a good approach?
    • Adjuvant ICI trials
      • ADMEC-O: Randomized Phase 2 Trial of Adjuvant Nivolumab Obs for completely resected MCC
        • Absolute risk reduction 1-year DFS 9%, relative risk 39%, no statistical significance
      • STAMP Trial
        • Risk of recurrence decreased from 29% to 17% in 1-year, relative risk ~41%, no statistical significance
      • Number needed to treat (NNT) analysis of ADMEC-O (11 NNT) and STAMP (8.3 NNT)
        • Adjuvant ICI benefits in some patients
        • ~60-70% of patients treated would never have recurred even without ICI
      • TOMMORRoW ctDNA+
        • 41 patients tracked using ctDNA, expected NNT of 3.0.
      • Could enhance both patients QoL and healthcare efficiency
        • Early initiation of ICI for subclinical MCC patients with positive ctDNA may improve outcomes
        • Could reduce
          • Unnecessary exposure to potential toxicities
          • Cost of therapy while decreasing number of patients needed to treat
        • Should ctDNA positive patients get immunotherapy- higher risk profile than stage
          • Eligible patients
            • Locoregional (Stage I-III) MCC
            • After initial curative treatment
            • No prior chemo/immunotherapy
          • Proposed trial design – plan to open through SWOG
            • Subclinical MCC patients with positive ctDNA & negative scans/physical exams
            • Randomized into Observation (standard of care) or Immunotherapy groups
            • Both receive ctDNA & scans concurrently every 3 months
            • Major endpoints:
              • Recurrence-free survival
              • MCC-specific & overall survival
              • Time to become ctDNA negative
            • Join trial development
              • Reach out to [email protected]
              • Outstanding discussion points:
                • ‘Optimal’ window to trial entry from negative scans & positive ctDNA: within 1 month?
                • ICI duration: 1 year vs 2 years?

7. An Updated MCC Recurrence Risk Calculator via International Collaborations

Aubriana McEvoy, MD

• Multi-variable recurrence risk calculator available at merkelcell.org/prognosis/recur
• 2 Upcoming Projects:
  • Project 1: Improving current recurrence risk calculator through external validation & implementing calculator adjustments.
    • Nearing end of recruitment, target data collection summer of 2026
  • Project 2: Recurrence Risk Calculator version 2.0, adding predictor variables (MCPyV viral status, ctDNA, Immunosuppression type, Treatment, LVI)
    • Site recruitment open
  • Very Preliminary Results
    • WashU & Stanford- preliminary validation cohort
    • UW- Model creation cohort
    • Table 1: Baseline patient and tumor characteristics
      • UW cohort younger with less immunosuppressed, path staging, H&N, & unknown primary compared to validation sites
    • Figure 1: Predicted risk of recurrence by stage and site
      • Significant spread of expected risk within stages driven by non-stage factors
      • Risk distribution overlap between stage II & III
      • Recurrence progression with stage as expected
    • Figure 2. Preliminary estimates of discrimination of 5-year recurrence risk
      • Based on C-index– measure of model performance
        • How well does the model discriminate between who will recur vs not recur?
      • In UW and validation cohort model does better than stage alone
      • Model worked worse in validation cohort– to be expected based on table 1 information
      • More data needed to improve calculator for better generalizability
    • Data sharing logistics updates
      • Opportunity for recurrence-focused related projects
        • DUA amendments & updated version available
          • If DUA stalled from PHI, DUA can be revised to be considered ‘limited data set’, reach out to Aubri & Rima
        • International collaboration- ‘limited data set’ option available (with time interval instead of dates)
      • Upcoming Dates:
        • May 2026: Next project newsletter
        • Summer 2026: Target deadline for Phase 1 data collection
          • Institutions unable to contribute data collection by Phase 1 deadline are welcome to participate in subsequent validation efforts and Phase 2 activities

8. How Much Has Immunotherapy Improved MCC Outcomes?

Sophia Shalhout, PhD (Harvard University)

• Aim: Evaluate the impact of immunotherapy adoption on MCC-specific survival
  • Approach using two Complementary Analyses:
    • Approach I: Population-Level Analysis
      • Surveillance, Epidemiology, and End Results (SEER)
    • Approach II: Treatment- Level Analysis
      • Single-Institution, Seattle Cohort in collaboration MC3 Institute at UW
    • Approach I: Population Level Analysis
      • Methods:
        • Retrospective analysis of MCC patients in SEER 17 (SEER*Stat 9.0.41)
        • Inclusion Criteria: AJCC Stage III-IV MCC, Diagnosis between 2011-2022, Systemic Therapy
        • Administrative cutoff at 2017 to define
          • pre-ICI era 2011-2016 (N=285) vs
          • ICI era 2017-2022 (N-141)
        • DSS defined as time from diagnosis to MCC-specific death, with censoring non-MCC death, last known follow-up, or the fixed calendar cutoff corresponding to the end of the treatment era.
      • Results:
        • Age, sex, race distribution similar between groups
        • Primary site different- more H&N and stage III in pre-ICI ere and more not specified sites and stage IV in ICI era
        • Kaplan-Meier 5-year MCC Specific Survival
          • 1% pre-ICI era
          • 46% ICI era
          • Approached significance (p=0.057)
        • Multivariable Regression MCC-Specific Survival
          • Pre-ICI and ICI era held, found to be statistically significant (p=0.015)
        • Conclusions:
          • In unadjusted analysis, the ICI era showed a trend toward improved MCC-specific survival
          • 5-year DSS increased from 33% pre-ICI to 46% in the ICI era
          • After adjustment, diagnosis in the ICI era was independently associated with improved DSS, with a 32% lower risk of MCC-specific death
          • Lower stage and female sex were also associated with improved DSS
        • Limitations:
          • Era was used as a proxy for ICI exposure
          • SEER does not capture key patient-level variables (MCPyV status, immunosuppression, timing of therapy initiation, type of systemic therapy)
            • Proportion of patients who actually received ICI in post-2017 era is unknown
          • DSS from diagnosis instead of treatment initiation weakens causal interpretation; Patients contribute survival time before receiving the exposure
        • Approach II: Treatment Level Analysis
          • Methods
            • Retrospective analysis of MCC patients from the Seattle Registry (1998-2024)
            • Inclusion Criteria:
              • First line systemic therapy (ICI or cytotoxic chemotherapy)
              • Propensity score matching (1:1) on logistic regression (stage, age, sex, MCPyV status, and immunosuppression) with nearest neighbor matching at caliper 0.2
              • Final cohort: ICI (N=133) and Chemotherapy (N=133)
              • DSS defined as time from initiation of first-line systemic therapy to MCC-specific death, with censoring at non-MCC death, last known follow-up, or 5-year fixed horizon
            • Results
              • Race p=0.05
              • Kaplan-Meier MCC-Specific Survival
                • 8% ICI
                • 9% Chemotherapy
              • Stage-Stratified Multivariable Regression DSS
                • Both treatments held and remained independently significant
                • HR= 0.32
                • p<0.0001
              • Conclusions:
                • ICI therapy was associated with improved DSS compared with cytotoxic chemotherapy
                  • 63% lower risk of MCC death (HR 0.37 univariable; 0.32 adjusted)
                  • 4-fold increase in 5-year survival
                • 5-year DSS was 56.8% with ICI vs 23.9% with chemotherapy
                • Survival benefit remained significant after propensity matching and multivariable adjustment
              • Limitations:
                • Retrospective, single-institution cohort
                • Potential for residual confounding despite propensity score matching
                • Treatment selection bias and temporal bias with evolving practice patterns and supportive care over time
                • Heterogeneity in chemotherapy regimens
                • Composite definition of immunosuppression
              • Summary:
                • Population trends and treatment-level evidence suggest immune ICI have improved survival in MCC
                  • SEER analysis demonstrates an era effect consistent with improved outcomes
                  • Seattle analysis confirms a significant direct treatment effect of ICI
                  • Together provide converging evidence that ICI therapy confers a large, durable survival benefit in MCC

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Goals of the Merkel cell carcinoma Multi-center Interest Group (MMIG) – Promote communication and collaborative studies on MCC – Enhance access to patient data and specimens – Expand evidence-based care for MCC

Homepage for MMIG is available at: https://merkelcell.org/about-us/mmig/

MMIG is funded in part by donations from Merkel cell carcinoma patients. Please note that in many cases, these summaries reflect unpublished data and are provided to help MMIG members manage their patients and give an overview of what is being done at different centers for care and research.

In attendance at the 2026 MMIG Meeting (N=83 total attendees)

Asterisk* = in-person attendee

We apologize if we missed your name or affiliation