Cosibelimab in Advanced Cutaneous Squamous Cell Carcinoma: ≥2-Year Follow-Up from the Pivotal Study

This video is sponsored by Sun Pharma. Its content is editorially independent of the sponsor. 

In this video segment, Rahul Ladwa, Medical Oncologist, reviews the updated ≥2-year follow-up results from the pivotal open-label study evaluating cosibelimab in advanced cutaneous squamous cell carcinoma (cSCC).

For dermatologists increasingly involved in the longitudinal management of high-risk and advanced cSCC, this discussion offers practical context on efficacy and safety, particularly in an older, comorbid population where tolerability matters.

From limited options to immune checkpoint inhibition

Until the emergence of immune checkpoint inhibitors, systemic options for advanced cSCC were limited. PD-1 pathway blockade significantly shifted the treatment paradigm.

Cosibelimab is currently the only FDA-approved PD-L1 inhibitor for advanced cSCC. Unlike PD-1 inhibitors, cosibelimab directly blocks PD-L1 and also targets B7.1, enhancing T-cell activation. In addition, its fully human monoclonal antibody structure enables antibody-dependent cellular cytotoxicity, offering a mechanistic distinction within the immunotherapy landscape.

The agent received FDA approval in 2024 following results from its pivotal phase 1 program in advanced malignancies, including cSCC.

Study design: pivotal phase 1 program

This was a multicenter, global, nonrandomized phase 1 study with 2 components:

• Part 1: Dose evaluation in advanced malignancies
• Part 2: Dose expansion cohorts in advanced cSCC

Cohorts

• Group 1: Metastatic cSCC (800 mg IV every 2 weeks)
• Group 2: Locally advanced, inoperable cSCC (800 mg IV every 2 weeks)
• Group 3: Metastatic cSCC (1200 mg IV every 3 weeks)

A total of 192 patients were enrolled:

• 78 in Group 1
• 58 in Group 2
• 56 in Group 3

Efficacy analyses focused on Groups 1 and 2. Safety was evaluated across all 3 cohorts.

Primary endpoint

• Overall response rate (ORR)
  • Independent central radiologic review (RECIST v1.1)
  • WHO digital classification (including photography-based assessment)

The JAAD update incorporated:

• An additional 16 months of follow-up
• Updated safety analyses (measured by treatment-emergent adverse events)

Patient population

Among 109 efficacy-evaluable patients:

• Median age: 70s
• Predominantly male and Caucasian
• Most had ECOG 0–1
• Many had prior surgery or radiotherapy
• Few had received prior systemic therapy

Efficacy: responses that deepen over time

Overall response rate

• Metastatic cSCC (Group 1): 50%
• Locally advanced cSCC (Group 2): 54.8%

Complete response rates

• Group 1: 12.8%
• Group 2: 25.8%

Notably, complete response rates improved compared to the initial publication:

• Group 1 increased from 7.7%
• Group 2 increased from 9.7%

This suggests that responses continue to deepen with extended follow-up, a clinically meaningful observation for dermatologists monitoring patients over time.

Safety: a critical consideration in this population

Treatment-emergent adverse events were common, as expected with immunotherapy. However, Grade 3 immune-related AEs only occurred in about 3.6% of patients.

In an elderly population with frequent comorbidities, tolerability is especially important. Adverse events can have outsized impact in patients with baseline cardiovascular, pulmonary, metabolic, or transplant-related complexities.

Dr Ladwa emphasizes that safety must be weighed carefully in patients with complex comorbidities like immunosuppression or organ transplantation; in such scenarios, nuanced risk–benefit discussions remain essential.

Key takeaways

• Cosibelimab is the only FDA-approved PD-L1 inhibitor for advanced cSCC
• Updated ≥2-year follow-up data demonstrate:
  • ORR ~50–55%
  • Increasing complete response rates over time
• Grade 3 immune-related AEs occurred in 3.6% of patients
• Safety profile is particularly relevant in older, comorbid patients
• Understanding mechanism and long-term data can support confident multidisciplinary discussions and prescribing decisions

For additional details, clinicians are encouraged to review the full publications accompanying this analysis.