BRIDGE Oncology™

NMSC By the Numbers

Fast Facts in NMSC BCC in the US

1st

Most common NMSC, accounting for 8 of 10 cases1,2

3.6M

Patients diagnosed each year3

Up to 0.55%

Cases metastasize3

>95%

5-year cure rate1

Male

Sex, older age, and light pigmented skin are at higher risk of NMSC2

The most significant contributor to NMSC is UV radiation exposure.2

BCC is the most common malignancy in humans, with its incidence growing exponentially.1,2 Mortality and metastasis are rare.3 BCC, basal cell carcinoma; M, million; NMSC, nonmelanoma skin cancer; UV, ultraviolet.

1. American Cancer Society (ACS). 2024. https://www.cancer.org/cancer/types/basal-and-squamous-cell-skin-cancer/about/what-is-basal-and-squamous-cell.html; 2. Puckett Y, Steele RB. In: StatPearls [Internet]. https://www.ncbi.nlm.nih.gov/books/NBK482439/; 3. Skin Cancer Foundation. https://www.skincancer.org/skin-cancer-information/basal-cell-carcinoma/.

Image: https://drgurgen.com/what-floridians-should-know-about-year-round-uv-exposure-and-skin-cancer/.

Fast Facts in NMSC cSCC in the US

2nd

Most common form of NMSC, accounting for 2 of 10 cases 1

1.8M

Patients diagnosed each year1

200%

Increased incidence over past 3 decades1

80%

Occur in people aged >60 years 2

1%-2%

Mortality rate; higher in central/southern states, with an annual death rate similar to melanoma and renal and oropharyngeal carcinomas 3

1.9%-2.6%

Rate of metastasis following excision of primary lesion4

>99%

5-year cure rate for localized; <50% when metastatic5

Up to 55% of all cSCC develop on the head and neck3

cSCC is among the most common cancers capable of metastasis. 4 cSCC, cutaneous squamous cell carcinoma.

1. Skin Cancer Foundation. https://www.skincancer.org/skin-cancer-information/squamous-cell-carcinoma/; 2. Fania L, et al. Biomedicines. 2021;9(2):171; 3. Karia PS, et al. J Am Acad Dermatol.

2013;68(6):957-966; 4. Brougham NDLS, et al. J Surg Oncol. 2012;106(7):811-815; 5. Moffitt Cancer Center. https://www.moffitt.org/cancers/squamous-cell-carcinoma/survival-rate.

Images: https://www.aad.org/public/diseases/skin-cancer/squamous-cell-carcinoma/pictures.

Why a Multidisciplinary Approach?

• Advanced NMSC is multifaceted – Wide range of presentations and responses to treatment

Dermatologist Medical oncologist

• Advanced tumors → require skills Surgical and expertise across oncologist many subspecialties working in coordination • Patient perspective important to Mohs surgeon ensure treatment choices match patient goals of therapy

Negbenebor NA. Cutis. 2021;107(5):E22-E23.

Medical subspecialist

Patient with advanced NMSC

Radiation oncologist

Primary care provider

Physician assistant, nurse or nurse practitioner, pharmacist

MANAGEMENT OF ADVANCED cSCC

Patients at High Risk for Multiple Primary cSCCs • Organ transplant recipients1 • Other settings of immunosuppression (eg, lymphoma, CLL, drug-induced, HIV)1 – Immunosuppression was significantly associated with LR (P<0.00001) and more likely to develop NM, DM, and experience DSD (P=0.027)2

• Genetic syndromes predisposing to cSCC formation (eg, xeroderma pigmentosum, Rothmund-Thomson syndrome, dyskeratosis congenita) 1 • Important individual risk factors include1 – Total number of tumors – Frequency of development – Occurrence of aggressive tumors (eg, extension beyond cutaneous structures, PNI, large and poorly differentiated, having ≥3 risk factors for recurrence)

CLL, chronic lymphocytic leukemia; DM, distant metastasis; DSD, disease-specific death; LR, local recurrence; NM, nodal metastasis; PNI, perineural involvement.

1. National Comprehensive Cancer Network® (NCCN®). 2026. https://www.nccn.org/professionals/physician_gls/pdf/squamous.pdf; 2. Lopez A, et al. Arch Dermatol Res. 2023;315(5):1429-1433.

SOTR cSCC Risk Probability of cSCC, by Transplanted Organa

• The annual incidence of cSCC was 1.69% in SOTRs and 0.30% in persons without transplantation (2009-2019) • The adjusted HR of cSCC was:

• Azathioprine use for ≥7 months associated with a 4.22-fold increased risk of cSCC • Each month of voriconazole use associated with a HR of 1.14 • No increased risk associated with use of tacrolimus, mycophenolate, everolimus, sirolimus, cyclosporine, and belatacept SOTR, solid organ transplant recipient; HR, hazard ratio. aP<0.0001 for every organ compared with no transplant, at 5 and 10 years.

Dusendang JR, et al. J Am Academ Dermatol. 2022;86(3):598-606.

Probability, %

– 14.83 for lung transplant – 10.69 for multiple organ transplants – 7.80 for heart transplant – 6.82 for kidney transplant – 6.53 for liver transplant

1.00

0.75

0.50

Transplant organ, number of cSCC cases

0.25

— No transplant, 914 — Kidney, 132 — Multiple, 13 — Heart, 14 — Liver, 63 — Lung, 24

0.00

0

1

2

3

4

5

6

7

8

Years Since Index Date

9

10

11

Risk Definitions/Classifications Low Risk

Moderate (or Increased) Risk

High Risk

Locally Advanced

CCPDMA, complete circumferential peripheral and deep margin assessment.

Courtesy of Vishal Patel, MD.

• Low risk for disease-specific poor outcomes, majority of tumors • Suitable for a variety of treatment options • Increased risk (for recurrence)

• Necessitate CCPDMA/Mohs surgery • High risk for NM/DM and DSD • Need treatment beyond just surgery • Tumors with potential regional nodal disease • Require multidisciplinary care

cSCC Risk Stratification and Staging • NCCN® Guidelines stratify into low-, high-, and very-high-risk groups; staging systems (AJCC-8, BWH, Breuninger, Tübingen) further refine prognosis1 • No single system perfectly predicts outcomes—NCCN guidance correlates imperfectly with outcomes data, so risk assessment guides rather than dictates a single path

BWH is most appropriate for predicting risk of poor outcomes in patients with HNcSCC (best specificity and positive predictive values compared to other systems).2

AJCC-8, American Joint Committee on Cancer 8th edition; BWH, Brigham and Women’s Hospital; HNcSCC, head and neck cSCC; NCCN ®, National Comprehensive Cancer Network.

1. NCCN®. 2026. https://www.nccn.org/professionals/physician_gls/pdf/squamous.pdf; 2. Elaldi R, et al. J Clin Med. 2023;12(12):3929.

cSCC Risk Stratification and Staging High-Risk Features to Recognize

CLINICAL

PATHOLOGIC

 Any tumor on head/face/neck, hands/feet, or anogenital area  ≥2 cm on trunk/extremities  Poorly defined or recurrent  Immunosuppression

 Poor differentiation  Aggressive histologic subtypes  PNI (≥0.1 mm)  Depth >6 mm or invasion beyond fat  Lymphovascular invasion

NCCN®. 2026. https://www.nccn.org/professionals/physician_gls/pdf/squamous.pdf.

Once High-Risk or Very High–Risk Criteria Are Met: ACT Refer to a multidisciplinary team—Mohs/dermatologic surgery, radiation oncology, and medical oncology, as indicated1 Consider imaging (CT/PET-CT) for nodal or deep-tissue involvement in higher-stage disease1

Consider systemic immunotherapy (anti–PD-1) for locally advanced or metastatic disease not curable by surgery or radiation1 Do NOT manage very high–risk disease with surgery alone— this is the referral trigger1,2 CT, computed tomography; PD-1, programmed cell death protein 1; PET, positron emission tomography.

1. NCCN®. 2026. https://www.nccn.org/professionals/physician_gls/pdf/squamous.pdf; 2. Elaldi R, et al. J Clin Med. 2023;12(12):3929.

Immune Checkpoint Inhibitors (ICIs) Rationale for immunotherapy:

TMB1 High levels of infiltrating regulatory T cells2

Tumor cell TCR

PD-L1

Antigen MHC

PD-1 T cell

Anti– PD-1

• High mutational burden 1 • Increased disease risk among immunosuppressed patients (eg, SOTRs)3 • Hypermutated tumors due to chronic skin damage from UV light4 • Patients with tumors with high TMB are more likely to respond to therapy with an ICI5

Treatment with cemiplimab and pembrolizumab have become the standard of care for advanced cSCC not amenable to curative surgery or radiation. 6 MHC, major histocompatibility complex; PD-L1, programmed death-ligand 1; TCR, T-cell receptor; TMB, tumor mutational burden; UV, ultraviolet.

1. Chalmers ZR, et al. Genome Med. 2017;9(1):34; 2. Hall ET, et al. Am Soc Clin Oncol Educ Book. 2020;40:1-10; 3. Euvard S, et al. N Engl J Med. 2003;348(17):1681-1691; 4. Pickering CR, et al. Clin Cancer Res. 2014;20(24):6582-6592; 5. Rizvi NA, et al. Science. 2015;348(6230):124-128; 6. NCCN®. 2026. https://www.nccn.org/professionals/physician_gls/pdf/squamous.pdf.

FDA-Approved ICIs for Advanced cSCC Cemiplimab-rwlc1

Pembrolizumab2

Cosibelimab-ipdl3

Initial cSCC Approval

2018 (advanced); 2025 (adjuvant)

2020

2024

Target/Class

Anti–PD-1/Human IgG4 mAb

Anti–PD-1/Humanized IgG4 mAb

Anti–PD-L1/Human IgG1 mAb

cSCC Indication

• Adults with m/lacSCC who are not candidates for curative surgery or RT • For the adjuvant treatment of adult patients with cSCC at high risk of recurrence after surgery + RT (Oct 2025)

Adults with recurrent or m/lacSCC who are not candidates for curative surgery or RT

Adults with m/lacSCC who are not candidates for curative surgery or RT

Dosing

m/lacSCC: 350 mg IV Q3W until disease progression, unacceptable toxicity, or ≤24 months Adjuvant: 350 mg Q3W for 12 wk OR 350 mg Q3W for12 wk then 700 mg Q6W until disease recurrence, unacceptable toxicity, or ≤48 weeks of total therapy

200 mg IV Q3W or 400 mg IV Q6W until disease progression, unacceptable toxicity, or duration up to 24 months

1,200 mg IV Q3W

Fatigue, musculoskeletal pain, rash, pruritus, diarrhea, anemia

Fatigue, musculoskeletal pain, rash, diarrhea, pyrexia, cough, decreased appetite, pruritus, dyspnea, constipation, pain, abdominal pain, nausea, and hypothyroidism

Fatigue, musculoskeletal pain, rash, diarrhea, hypothyroidism, constipation, nausea, headache, pruritus, edema, localized infection, and urinary tract infection

Most Common AEs

Monitoring

Evaluate liver enzymes, creatinine, and thyroid function at baseline and periodically during treatment

AE, adverse event; FDA, US Food and Drug Administration; IgG, immunoglobulin G; IV, intravenous; mAb, monoclonal antibody; m/lacSCC, metastatic or locally advanced cSCC; Q3W, every 3 weeks; Q6W, every 6 weeks; RT, radiation therapy; wk, week.

1. Drugs@FDA. https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/761097s032lbl.pdf; 2. Drugs@FDA. https://www.accessdata.fda.gov/drugsatfda_docs/label/2026/125514s187lbl.pdf; 3. Drugs@FDA. https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/761297s001lbl.pdf.

Adjuvant Anti–PD-1 in High-Risk cSCC Divergent Trial Outcomes

Approved: Adjuvant Cemiplimab (C-POST)1 Trial Design

Phase 3, randomized, double-blind, placebo-controlled; N=415 patients randomized to cemiplimab or placebo

Population

Resected high-risk cSCC after surgery + PORT ± nodal features

Regimen

Cemiplimab 350 mg IV Q3W for 12 wk, then 700 mg IV Q6W or placebo for a total of 48 wks

Primary Endpoint

DFS

Result

• Met primary endpoint; estimated 24-month DFS: 87.1% with cemiplimab vs. 64.1% with placebo • ASCO 2026: adjuvant cemiplimab demonstrated a DFS benefit vs. placebo across all high-risk features and regardless of the interval between prior RT completion and randomization 2

Status

FDA-approved October 2025 NCCN Category 1 preferred option for very-high-risk cSCC4

Adjuvant Pembrolizumab Failed (KEYNOTE-630)3 • Study population – 450 patients with resected high-risk locally advanced cSCC after surgery + PORT (phase 3, placebo-controlled)

• Why it failed – Did not meet primary endpoint (RFS) – No significant survival benefit vs placebo – Stopped early for futility (Aug 2024)

ASCO, American Society of Clinical Oncology; DFS, disease-free survival; PORT, postoperative radiation therapy; RFS, recurrence-free survival.

1. Rischin D, et al. N Engl J Med. 2025;393(8):774-785; 2. Rischin D, et al. Presented at: 2026 ASCO Annual Meeting; May 29-June 2, 2026; Chicago, IL. Abstract 6083; 3. Koyfman SA, et al. J Clin Oncol.

2025;43(suppl 16):6000; 4. NCCN®. 2026. https://www.nccn.org/professionals/physician_gls/pdf/squamous.pdf.

Neoadjuvant Anti–PD-1 Agents in Resectable cSCC CEMIPLIMAB1

PEMBROLIZUMAB 2 Phase 2 Trials

Phase 2 Resectable stage II-IV (M0) cSCC; stage II only if primary tumor >3 cm Nonrandomized; N=79

De-Squamate2 Resectable stage II-IV (M0) cSCC; N=27

PD-1 naive, resectable locally advanced cSCC (≥T3 orT2 with ≥2 BWH high-risk features, ± nodal disease); N=26 3

Regimen

350 mg IV Q3W for up to 4 doses, then surgery

200 mg IV Q3W for 2-4 cycles; patients only proceeded to surgery and RT in the absence of cCR; RT was de-escalated if pCR or MPR

200 mg IV Q3W for 2 cycles prior to definitive surgery, and 15 cycles post-surgery

Primary Endpoint

pCR

cpCR

pCR

Efficacy Data

pCR: 51% • MPR: 13% ORR: 68%

cpCR: 63% pCR: 15% • cCR: 48% ORR: 66%

pCR: 57%

Safety

TRAE: 72%; Grade ≥3: 18% Most common: fatigue, maculopapular rash, and diarrhea

TRAEs: 74%; Grade ≥3: 41% Most common: fatigue, pruritus, diarrhea, nausea, and arthralgia

AEs: Grade 3: 2 (hepatitis, colitis); Grade 5: 1 (NSTEMI)

Population

cCR, clinical complete response; cpCR, clinical or pathologic complete response; irAE, immune-related AE; pCR, pathologic CR; mo, month; MPR, major pathologic response; NSTEMI, non – ST-segment elevation myocardial infarction; ORR, objective response rate; pts, patients; T, tumor; TRAE, treatment-related AE. 1. Gross ND, et al. N Engl J Med. 2022;387(17):1557–1568; 2. Ladwa R, et al. J Clin Oncol. 2025;43(26):2888-2896; 3. Amatore F, et al. J Clin Oncol. 2024;42(suppl 16):9591.

NCCN Guidelines

When to Consider Immunotherapy?

Very-high–risk cSCC with significant risk of extensive local recurrence, nodal, or in-transit metastasis

Consider neoadjuvant therapy with cemiplimab if: • Nonreactive nonkeratoacanthomatous rapid growth tumors • In-transit metastasis • Borderline resectable • Surgery alone may not be curative or may result in significant functional limitation

Consider adjuvant therapy with cemiplimab following adjuvant RT in patients with extremely high–risk nodal and nonnodal features

1L, first line.

NCCN®. 2026. https://www.nccn.org/professionals/physician_gls/pdf/squamous.pdf.

lacSCC that is primary or recurrent extensive disease, for which surgery and/or RT may not result in a cure or would possibly produce a significant functional impairment Surgical Candidates: Consider neoadjuvant therapy with cemiplimab and/or clinical trial after multidisciplinary discussion

Nonsurgical Candidates: Consider RT ± systemic therapy, or systemic therapy if curative RT not feasible

Incorporating Immunotherapy Into Patient Care Identify which patients are candidates for treatment Consider those patients requiring rapid decrease in tumor burden and/or durable disease control Continually reassess for ability to resect Potential combinations in the future Courtesy of Vishal Patel, MD.

Neoadjuvant Immunotherapy Practical Considerations How long to treat prior to surgery?

Delay of surgery, an issue?

• Unclear

• Unclear

– Additional doses of immunotherapy did not appear to yield higher pCR

– 2 preoperative doses of cemiplimab 1

•2 preoperative doses of cemiplimab1 – pCR or MPR 70%

•4 preoperative doses of cemiplimab2 – pCR or MPR 63%

1. Ferrarotto R, et al. Clin Cancer Res. 2021;27(16):4557-4565; 2. Gross ND, et al. N Engl J Med. 387(17):1557-1568.

•0/20 cases failed to have surgery in study window

– 4 preoperative doses of cemiplimab 2 •11% cases failed to have surgery in study window

Referring to Oncology

When to Refer and What Oncology Adds Only ≈43% of patients with advanced NMSC seen per dermatologist each year are referred1 WHEN TO REFER High-risk tumor features: ≥2 cm, invasion beyond fat or >6 mm depth, poor differentiation, PNI (≥0.1 mm), or LVI2 Advanced stage: BWH T2b/T3 or AJCC-8 T3/T4—highest risk of metastasis and death3 High-risk host factors: immunosuppression or SOTR; rapidly growing, recurrent, or in-transit disease2 Not curable by surgery/RT: locally advanced or metastatic disease—candidate for systemic ICI2

WHAT ONCOLOGY ADDS Staging and workup, including systemic therapy selection and irAE management 2,5 Transplant coordination5

CV monitoring6

Adjuvant candidate (NEW): resected very high–risk cSCC after surgery + RT—Category 1 for adjuvant cemiplimab4 Any node-positive disease: regional nodal involvement warrants tumor board input2 LVI, lymphovascular invasion.

1. Integritas Communications Group. Clinical Needs Assessment Panel: Advanced NMSC survey data, 2026; 2. NCCN®. 2026. https://www.nccn.org/professionals/physician_gls/pdf/squamous.pdf; 3. Ruiz ES, et al. JAMA Dermatol. 2019;155(7):819-825; 4. Rischin D, et al. N Engl J Med. 2025;393(8):774-785; 5. NCCN®. 2025. https://www.nccn.org/professionals/physician_gls/pdf/ici_tox.pdf; 6. Drobni ZD, et al.

Circulation. 2020;142(24):2299-2311.

MANAGEMENT OF ADVANCED BCC

Management of BCC Lesions Surgical excision

Local destruction

Vast majority of BCC lesions are highly curable and easy to treat

Mohs micrographic surgery

RT

Remain untreated

NCCN®. 2026. https://www.nccn.org/professionals/physician_gls/pdf/nmsc.pdf.

• Small minority of patients develop surgically unresectable locally advanced or metastatic disease

NCCN

Risk Factors for BCC LOW RISK

HIGH RISK

HISTORY AND PHYSICAL Location/Size

Trunk, extremities <2 cm

Trunk, extremities >2 cm Any size: head, neck, pretibial, mask areas of face, anogenital area, hands, and feet

Clinical Borders

Well defined

Poorly defined

Primary vs Recurrent

Primary

Recurrent

Immunosuppression

─

+

Site of Prior RT

─

+

PATHOLOGY Subtype

Nodular, superficial

Aggressive growth pattern: having (mixed) infiltrative, micronodular, morpheaform, basosquamous, sclerosing, or carcinosarcomatous differentiation in any tumor portion

Perineural Involvement

─

+

Adapted from NCCN®. 2026. https://www.nccn.org/professionals/physician_gls/pdf/nmsc.pdf.

Factors Predictive of Recurrence, Metastasis, or Death Multivariable Logistic Regression: BCC Tumors ≥2 cm

1

Head and Neck Location

2

Diameter ≥4 cm

3

Tumor Depth Beyond Subcutaneous Fat

4

Treatment Modality: Mohs Surgery

9.7× higher odds of local recurrence • 5.3× higher odds of metastasis/death

11.9× higher odds of metastasis/death

3.1× higher odds of local recurrence • 28.6× higher odds of metastasis/death (strongest predictor)

86% lower odds of local recurrence when Mohs was used (protective factor)

Small BCC (<2 cm): no metastasis or death occurred in this cohort, vs 6.5% in the ≥2 cm group (P<0.001).

Morgan FC, et al. J Am Acad Dermatol. 2020;83(3):832-838.

BCC Risk Stratification and Staging • NCCN stratifies BCC into low- and high-risk groups (location/size, borders, recurrence, immunosuppression, prior RT, histologic subtype, perineural invasion); BWH and AJCC-8 staging further refine prognosis for head/neck disease1 • BCC rarely metastasizes, so no single system perfectly predicts outcomes—risk stratification guides surveillance and treatment intensity rather than dictating a single path1,2

The BWH BCC system is most appropriate for predicting risk of metastasis or death.2 1. NCCN®. 2026. https://www.nccn.org/professionals/physician_gls/pdf/nmsc.pdf; 2. Morgan FC, et al. J Am Acad Dermatol. 2021;85(3):582-587.

BCC Risk Stratification and Staging High-Risk Features to Recognize

CLINICAL

PATHOLOGIC

 Mask areas of face, genitalia, hands/feet—any size1  ≥1 cm on head/neck/pretibia1  ≥2 cm on trunk/extremities1  Recurrent tumor or prior RT at site1  Immunosuppression1

 Aggressive subtype (infiltrative, morpheaform, basosquamous, micronodular)1  PNI (>0.1 mm or below dermis)1,2  Invasion beyond subcutaneous fat (BWH T2 risk factor)2

1. Adapted from NCCN®. 2026. https://www.nccn.org/professionals/physician_gls/pdf/nmsc.pdf; 2. Morgan FC, et al. J Am Acad Dermatol. 2021;85(3):582-587.

Once High-Risk Criteria Are Met: ACT • Refer to a multidisciplinary team—Mohs/dermatologic surgery, radiation oncology, and medical oncology as indicated1 • Consider imaging (CT/MRI) for perineural or deep-tissue involvement in higher-stage (BWH T2) disease1,2 • Consider systemic therapy: HHI (vismodegib/sonidegib) 1L for locally advanced/metastatic disease not curable by surgery or radiation; cemiplimab reserved for progression on or intolerance to HHI1 • Do NOT manage BWH T2 (high-risk) disease with surgery alone— 10-year cumulative metastasis/death risk is 37% vs 0 in T1 2 HHI, hedgehog pathway inhibitor.

1. NCCN®. 2026. https://www.nccn.org/professionals/physician_gls/pdf/nmsc.pdf; 2. Morgan FC, et al. J Am Acad Dermatol. 2021;85(3):582-587.

Systemic Therapy for BCC Other Recommended

Useful in Certain Circumstances

None

• Vismodegiba (category 2Bb)

Cemiplimab-rwlcd (category 2Bb)

Locally Advanced Disease

None

• Sonidegib • Vismodegibc

Cemiplimab-rwlcd

Nodal Disease

None

• Vismodegib • Sonidegib

Cemiplimab-rwlcd

None

Cemiplimab-rwlcd

Preferred Locally Advanced Disease—Neoadjuvant

Metastatic Disease

Vismodegib

laBCC, locally advanced BCC; mBCC, metastatic BCC. aIn one study of 55 patients with laBCC, neoadjuvant administration of vismodegib before planned surgery allowed for a smaller surgical procedure in 71% of patients, although it carried a high (36.4%) recurrence risk; bCategory 2B indicates that the recommendation is based upon lower-level evidence, but there is NCCN consensus that the intervention is appropriate (≥50%, but <85% support of the panel); cIn certain circumstances, RT can be combined with vismodegib; dCemiplimab-rwlc is FDA approved for patients with laBCC or mBCC previously treated with an HHI or for whom an HHI is not appropriate; the role of adjuvant systemic therapy for resected BCC is unclear and, thus, it is best performed in a clinical trial setting.

NCCN®. 2026. https://www.nccn.org/professionals/physician_gls/pdf/nmsc.pdf.

First-Line HHIs

Vismodegib1-3

Sonidegib4-6

Primary Endpoint ORR

laBCC 43% mBCC 30% median DOR 7.6 months

laBCC 43% mBCC 15% 200-mg dose; data to 6 months

Long-Term Follow-Up ORR

laBCC: 60.3% • mBCC: 48.5% 39-month analysis

laBCC: 56% • mBCC: 8% 42-month cutoff

Dosing

150 mg orally QD

200 mg orally QD (take on empty stomach)

AEs

Muscle spasms, alopecia, dysgeusia, weight loss, fatigue, nausea, diarrhea, decreased appetite, constipation, arthralgias, vomiting, and ageusia ≈21% discontinued due to AEs

Muscle spasms, alopecia, dysgeusia, weight loss, fatigue, nausea, musculoskeletal pain, diarrhea, decreased appetite, myalgia, abdominal pain, headache, pain, vomiting, and pruritus ≈34% discontinued due to AEs

FDA Approval

2012 Adults with mBCC, or laBCC recurring after surgery or in those who are not candidates for surgery/RT

2015 Adults with laBCC recurring after surgery/RT or those who are not candidates for surgery/RT

ERIVANCE, Phase 2

BOLT, Phase 2

“Due to the frequency of intolerable side effects associated with HHIs, drug holidays or other alternatives to daily dosing can be used to reduce side effects to improve adherence to therapy and quality of life.”7 DOR, duration of response; CK, creatine kinase; GI, gastrointestinal; QD, once daily.

1. Sekulic A, et al. N Engl J Med. 2012;366(23):2171–2179; 2. Sekulic A, et al. BMC Cancer. 2017;17(1):332; 3. Drugs@FDA. https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/203388s017lbl.pdf; 4.

Migden MR, et al. Lancet Oncol. 2015;16(6):716–728; 5. Dummer R, et al. Br J Dermatol. 2020;182(6):1369–1378; 6. Drugs@FDA. https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/205266s009lbl.pdf; 7. NCCN®. 2026. https://www.nccn.org/professionals/physician_gls/pdf/nmsc.pdf.

Cemiplimab

FDA-Approved Indications for BCC laBCC1

mBCC1

• Cemiplimab is indicated for the • Cemiplimab is indicated for the treatment of adults with laBCC treatment of adults with mBCC previously treated with an HHI or previously treated with an HHI or for whom an HHI is not appropriate for whom an HHI is not appropriate

Also recommended (in certain circumstances) for neoadjuvant treatment of laBCC.2 1. Drugs@FDA. https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/761097s032lbl.pdf; 2. NCCN ®. 2026. https://www.nccn.org/professionals/physician_gls/pdf/nmsc.pdf.

Real-World Evidence

Cemiplimab for Advanced BCC Retrospective, multicenter real-world study (ADOREG registry) TRIAL DESIGN Patients (N=37)1 laBCC or mBCC treated with cemiplimab across 17 German skin cancer centers

Line of therapy1

Cemiplimab 2 350 mg IV every 3 weeks up to 93 weeks

1L (n=8) vs 2L after HHI progression/intolerance (n=29)

Pivotal Phase 2Trial Context • laBCC ORR 32.1% 2

Study endpoints: ORR, PFS, OS

• mBCC ORR 22% 3

KEY EFFICACY1

• HHI reinduction after progression on 2L cemiplimab: ORR 20.0%, median PFS 3.8 mo1

1L ORR: 62.5%

2L ORR: 31.0%

1L (median) PFS: 19.8 mo

2L (median) PFS: 5.3 mo

2L, second line; PFS, progression-free survival; OS, overall survival.

1. DeTemple VK, et al. Eur J Cancer. 2025;225:115590; 2. Stratigos A, et al. J Am Acad Dermatol. 2024;90(2):414–418; 3. Lewis KD, et al. Ann Oncol. 2024;35(2):221–228.

When to Refer to Oncology Advanced BCC

WHEN TO REFER1 laBCC: primary or recurrent extensive disease for which surgery and/or RT may not be curative or would cause significant functional/cosmetic impairment Nodal or metastatic disease: any regional nodal or distant metastasis; rare, but requires systemic therapy and multidisciplinary management HHI candidate or failure: advanced BCC for 1L HHI (vismodegib/sonidegib) OR progression/intolerance warranting 2L cemiplimab Aggressive or deeply invasive tumors: basosquamous, infiltrative, morpheaform, or sarcomatoid subtypes; bone, named-nerve, or deep soft-tissue involvement

WHAT ONCOLOGY ADDS • Staging and workup1 • HHI initiation and monitoring1 • Sequencing to cemiplimab1 • Transplant and CV care coordination2

Genetic syndromes: basal cell nevus (Gorlin) syndrome or xeroderma pigmentosum—refer for genetic evaluation and consider systemic/surveillance strategies Multidisciplinary decision needed: when treatment choice spans surgery, RT, HHIs, immunotherapy, or clinical trials, tumor board input is strongly encouraged

Most BCCs are cured locally, but advanced disease needs systemic therapy and multidisciplinary coordination.1,3 CV, cardiovascular.

1. NCCN®. 2026. https://www.nccn.org/professionals/physician_gls/pdf/nmsc.pdf; 2. Drobni ZD, et al. Circulation. 2020;142(24):2299-2311; 3. Peris K, et al. Eur J Cancer. 2023;192:113254.

IMMUNE-RELATED ADVERSE EVENTS

AEs Associated With Immunotherapy1 Pneumonitis Neurologic toxicities

Solid organ transplant rejection Nephritis and renal dysfunction

irAEs can occur in any organ system or tissue1

Colitis

Hepatitis

Endocrinopathies Dermatologic reactions Myocarditis

• Majority of irAEs occur within 3 months after initiation2 – First onset has been documented as long as 1 year after discontinuation of ICI

• irAEs are often dose dependent, potentially irreversible, and may be serious or lifethreatening2 – Can affect up to 71.5% of patients 3 – Mortality rate: 0.36% to 1.23% 3

• Lead to permanent discontinuation of cancer treatment in 10% to 20% of patients receiving ICI monotherapy or combination3

Identifying and managing irAEs can be difficult due to variable presentation, overlap with paraneoplastic syndromes or side effects from other chemotherapy treatments, and the absence of reliable biomarkers or diagnostic tests.3 1. Drugs@FDA. https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/761097s032lbl.pdf; 2. Haanen JBAG, et al. Ann Oncol. 2022;33(12):1217-1238; 3. Liao K, et al. Internal Med J. 2025;55:1794-1804.

Immunotherapy and CV Events • Inflammation and immune activation are key elements of the pathophysiology of atherosclerosis1 – Immune checkpoints (PD-1 and CTLA4) are important negative regulators of atherosclerosis1

• ICI therapy has been associated with a 3× increase in CV events, including MI, revascularization, and stroke2 • Highlights the importance of risk stratification and patient selection when using immunotherapy in NMSC population CTLA, cytotoxic T-lymphocyte-associated protein 4; MI, myocardial infarction.

1. Suero-Abreu GA, et al. Cardio Oncol. 2022;4(5):598-615; 2. Drobni et al. Circulation. 2020;142:2299-2311.

Dermatologic irAEs

Grading and Management per NCCN Guidelines INCREASING SEVERITY / BODY SURFACE AREA INVOLVEMENT → Maculopapular Rash

G1

G2

G3

Macules/Papules covering 10%–30% BSA; limiting iADLs

Macules/Papules covering >30% BSA or life-threatening; ADLs limited

Management Topical emollient + moderate-potency topical steroids; consider oral antihistamines

Management Topical emollient + moderate- to high-potency topical steroids; consider oral antihistamines; if unresponsive to topical within 1–2 weeks, consider prednisone; consider dermatology consult

Management High-potency topical steroids; prednisone/IV methylprednisolone; urgent dermatology consult, consider biopsy; consider inpatient care

Continue ICI

Continue ICI

Hold ICI

Macules/Papules covering <10% BSA

Pruritus G1

Mild/Localized

G2

G3

Intense/Widespread (intermittent); skin changes from scratching; limiting iADLs

Intense/Widespread (constant); limiting self-care ADLs or sleep

Management Oral antihistamines; moderate-potency topical steroids; consider OTC topical anesthetic/anti-itch creams

Management Oral antihistamines; prednisone/IV methylprednisolone; consider gabapentinoids, if no response in 1 month, consider dupilumab, omalizumab, or NB-UVB; urgent dermatology consult

Continue ICI

Hold ICI

ADL, activity of daily living; BSA, body surface area; G, grade; iADL, instrumental ADL; NB-UVB, narrow-band ultraviolet light B; OTC, over the counter.

NCCN®. 2025. https://www.nccn.org/professionals/physician_gls/pdf/ici_tox.pdf.

Bullous Dermatitis and SJS/TEN A Severity Continuum

INCREASING SEVERITY/BSA INVOLVEMENT → Grade 1

Grade 2

Grade 3/4

<10% BSA, asymptomatic

10%–30% BSA; painful blisters; iADLs limited

>30% BSA; limiting self-care ADLs; associated with fluid or electrolyte abnormalities

SJS/TENa

Management

Management

Management

Management

High-potency topical steroid

Prednisone/IV methylprednisolone; if no improvement after 3 days, urgent dermatology consult (if no access to dermatology, consider inpatient care); if bullous pemphigoid confirmed by biopsy or serology, consider rituximab or dupilumab

Prednisone/IV methylprednisolone; if bullous pemphigoid confirmed, use dupilumab as steroid-sparing measure; consider alternative steroid-sparing options (eg, IVIG) as an adjunct to rituximab; inpatient care required; urgent dermatology consult

Prednisone/IV methylprednisolone; evaluate entire medication list for alternative culprit drug; urgent dermatology, ophthalmology and urology consults; consider IVIG; other immunosuppressive therapies; inpatient care required

Consider Holding ICI

Hold ICI until <G1

Discontinue ICI

Discontinue ICI

IVIG, intravenous immunoglobulin; SJS, Stevens-Johnson syndrome; TEN, toxic epidermal necrolysis. aNCCN grades SJS/TEN as an extension of severe (grade 3/4) bullous dermatitis, so management escalates along one continuous scale.

NCCN®. 2025. https://www.nccn.org/professionals/physician_gls/pdf/ici_tox.pdf.

Lichenoid Disease and Psoriasiform Rash Severity-Based Management Moderate

Mild

10%–30% BSA or not responsive to high-potency topical steroids

<10% BSA

Severe >30% BSA

LICHEN PLANUS/LICHENOID DISEASE High-potency topical steroid or topical tacrolimus

High-potency topical steroid/tacrolimus; oral antihistamines; prednisone; consider referral to dermatology; NB-UVB if available; if not responsive, treat as severe

High-potency topical steroid/tacrolimus; prednisone/IV methylprednisolone; consider referral to dermatology, steroid-sparing immunosuppressants, dupilumab, or acitretin;

Continue ICI

Hold ICI

Hold ICI

High-potency topical steroid; consider nonsteroidal topical therapies (eg, tacrolimus or calcipotriene) for long-term management in intertriginous areas or facial location

High-potency topical steroid; consider nonsteroidal topical therapies for long-term management in intertriginous areas or facial location; NB-UVB; consider apremilast, acitretin, or approved biologics; if not responsive, treat as severe; Refer to dermatology

High-potency topical steroid; consider nonsteroidal topical therapies for long-term management in intertriginous areas or facial location; NB-UVB; consider apremilast, acitretin, cyclosporine, methotrexate, or approved biologics; if not responsive, treat as severe; Refer to dermatology

Continue ICI

Hold ICI

Hold ICI

PSORIASIS/PSORIASIFORM DISEASE

NCCN®. 2025. https://www.nccn.org/professionals/physician_gls/pdf/ici_tox.pdf.

The Community Dermatologist’s Role in irAE Management Why Dermatology Is Central1

Dermatologist Role1,2

• Cutaneous toxicities are the most common irAE overall

• Grade severity using NCCN BSA/symptom criteria

• Onset is early: median 3 weeks, well before most other organ irAEs (eg, renal irAEs, median 16.3 weeks)

• Biopsy when the diagnosis is unclear (eg, lichenoid vs psoriasiform)

• Dermatologists are frequently the first clinician to evaluate a new ICI-related rash—often before oncology does

• Treat Grade 1/2 presentations directly in most cases— largely reversible within 2 weeks • Communicate a clear continue/hold/discontinue recommendation back to the oncology team

When Oncology Will Escalate to Dermatology Urgently 2 • Grade 3/4 disease of any type (>30% BSA, bullous, or life-threatening features) • Any SJS/TEN features—same-day dermatology consult • Bullous disease with systemic symptoms or mucosal involvement • Diagnostic uncertainty affecting the oncology team’s continue/hold decision 1. Geisler AN, et al. J Am Acad Dermatol. 2020;83(5):1255-1268; 2. NCCN®. 2025. https://www.nccn.org/professionals/physician_gls/pdf/ici_tox.pdf.

Follow-Up

The Dermatologist Role: ❑ Complete skin exam every 6 to 12 months for first 5 years, then annually ❑ Education on sun protection and self-examination ❑ Strongly recommended follow-up if: ❑ Past or imminent solid organ, marrow, or hematopoietic cell transplant ❑ ≥1 cutaneous melanomas in past 5 years ❑ ≥4 NMSCs in past 5 years

Adapted from NCCN®. 2026. https://www.nccn.org/professionals/physician_gls/pdf/nmsc.pdf.

Take Note!

• 30% to 50% of patients with BCC will develop another BCC within 5 years • Patients with a prior BCC are also at increased risk of developing SCC and cutaneous melanoma

Care Coordination, Communication, and the Dermatologist’s Role Communication Framework

Practical Tools

• Dermatologists are the primary relationship for patients with NMSC—they are best positioned to notice subtle changes, counsel on adherence, and serve as the bridge to oncology • Formal survivorship care plans, standardized referral pathways, and shared follow-up protocols improve coordination

• Tumor board participation (in-person or virtual/on-demand) enables real-time input from radiation oncology, head/neck surgery, medical oncology, pathology

Courtesy of Vishal Patel, MD.

• Patient navigators can coordinate imaging, financial assistance, specialist scheduling, and trial enrollment • Clear documentation: for patients transitioning between community and academic care, the treating oncologist should provide a written post-treatment plan for monitoring/follow-up

National Resources: NMSC NCCN Guidelines for Patients® Basal Cell Skin Cancer, Squamous Cell Skin Cancer: 2026 The Skin Cancer Foundation provides prevention, early detection, and treatment information, as well as a Physician Finder The American Academy of Dermatology (AAD) offers patient education, free skin cancer screenings, and a board-certified dermatologist locator AIM at Skin Cancer provides skin cancer education to patients, caregivers, and families, with easy-to-understand information on prevention and early detection, treatment, side effects, and survivorship

GW Catchment Area Resources GW Cancer Center Cutaneous Oncology Program offers comprehensive, personalized, skin cancer care Cancercenter.gwu.edu Inova Life with Cancer provides free support to anyone affected by cancer, including nurse navigation, classes, counseling, and support groups across DC/MD/VA Lifewithcancer.org Nueva Vida offers bilingual cancer navigation and support to the underserved Latino community in the Washington, DC metropolitan area Nueva-vida.org

Visit Our Clinical Resource Center at https://exchangecme.com/group-events/BRIDGENMSC

Conclusions • Advanced NMSC is under-recognized and under-referred, making early identification of high-risk disease the critical first step • Staging drives management—the BWH system outperforms AJCC-8 for both cSCC and BCC in identifying patients at risk for metastasis and death • In cSCC, anti–PD-1 agents are 1L for advanced disease, with cemiplimab now FDA approved in the adjuvant setting • In BCC, cemiplimab is the only approved ICI—2L after HHI failure, with more modest responses reflecting lower immunogenicity • irAEs can affect any organ and follow a grade-based management framework, requiring baseline monitoring, patient education, and early recognition • The dermatologist is the frontline observer and key referral link (eg, to oncology) • Closing the referral gap is the central goal of coordinated NMSC care