CHMP Recommends Expanded Approval for 2 Pembrolizumab Indications

The agency has recommended approval for subcutaneous pembrolizumab in all previous solid tumor indications, and for pembrolizumab in recurrent HNSCC.

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended approval for pembrolizumab (Keytruda) in 2 indications, according to a press release from the developer, Merck.1

The European Commission is going to review the CHMP recommendations for marketing authorization in the EU, Iceland, Liechtenstein, and Norway; final decisions are anticipated to come in the fourth quarter of 2025.

The first recommendation was for the approval of pembrolizumab as subcutaneous administration and as a new pharmaceutical solution for injection; if approved, this indication would be marketed in the EU as Keytruda SC. The second recommendation was for the approval of pembrolizumab in locally advanced head and neck squamous cell carcinoma (HNSCC).

“Building on the legacy of [pembrolizumab], we are committed to driving innovation in cancer care with new routes of administration and indications in difficult-to-treat and earlier stages of cancer,” said Marjorie Green, MD, senior vice president and head of oncology, global clinical development, Merck Research Laboratories, in the press release.1 “This is a significant step forward in our pursuit of bringing this therapy to more patients. If approved, we believe [subcutaneous pembrolizumab] has the potential to provide meaningful benefits to patients and providers in Europe because it can offer a shorter administration time compared to [intravenous pembrolizumab] and the option to receive treatment in additional health care settings.”

Subcutaneous Pembrolizumab in Solid Tumors

Specifically, the CHMP opinion was for pembrolizumab as a subcutaneous injection administered by a health care provider. The agent would be administered at 395 mg as a 1-minute injection every 3 weeks, or at 790 mg as a 2-minute injection every 6 weeks; as a subcutaneous injection, the medication could be administered in multiple settings. The CHMP’s recommendation applied to all pembrolizumab indications for adult patients in Europe.

The new formulation of subcutaneous pembrolizumab contains pembrolizumab and berahyaluronidase alfa.

Supportive results came from the open-label phase 3 3475A-D77 trial (NCT05722015), which evaluated subcutaneous pembrolizumab vs intravenous pembrolizumab administered every 6 weeks, both with chemotherapy, in patients with treatment-naïve metastatic non–small cell lung cancer (NSCLC); these results were simultaneously shared at the European Lung Cancer Congress in March 2025 and published in Annals of Oncology.2

The overall exposure and trough concentration levels of subcutaneous pembrolizumab at 790 mg once every 6 weeks were noninferior to what was observed for intravenous pembrolizumab at 400 mg every 6 weeks.

Additionally, the overall response rate (ORR) was 45.4% (95% CI, 39.1%-51.8%) in the subcutaneous pembrolizumab arm vs 42.1% (95% CI, 33.3%-51.2%) in the intravenous pembrolizumab arm (ORR ratio, 1.08; 95% CI, 0.85-1.37). The median duration of response was 9.1 months vs 8.0 months, respectively.

The median progression-free survival (PFS) was 8.1 months (95% CI, 6.3-8.3) with subcutaneous pembrolizumab vs 7.8 months (95% CI, 6.2-9.7) with intravenous pembrolizumab (HR, 1.05; 95% CI, 0.78-1.43). The overall survival (OS) event rate was 24.3% vs 29.4%, although the median OS was not reached as of data cutoff (HR, 0.81; 95% CI, 0.53-1.22).

In September 2025, the FDA approved subcutaneous pembrolizumab based on data from the MK-3475A-D77 trial.3

Pembrolizumab in Locally Advanced HNSCC

The second CHMP recommendation was for patients with resectable locally advanced HNSCC whose tumors express PD-L1 with a combined positive score (CPS) of at least 1, and is as follows: pembrolizumab monotherapy as neoadjuvant treatment, then continued as adjuvant treatment in combination with radiation therapy with or without concomitant cisplatin, and finally as monotherapy.

Data supporting the recommendation from the phase 3 KEYNOTE-689 trial (NCT03765918), which evaluated the pembrolizumab-based regimen vs radiotherapy given after surgery alone, were published in the New England Journal of Medicine.4

With a median follow-up of 38.3 months, the 36-month event-free survival (EFS) rate was 58.2% in the pembrolizumab group vs 44.9% in the control group in the population of patients with a CPS of 1 or more; the median EFS was 59.7 months (95% CI, 37.9-not reached) vs 29.6 months (95% CI, 19.5-41.9), respectively (HR, 0.70; 95% CI, 0.55-0.89; P = .003).

The 3-year OS rate was 69.0% (95% CI, 63.3%-74.0%) in the pembrolizumab group vs 60.2% (95% CI, 54.1%-65.8%) in the control group across the CPS of 1 or more population (HR, 0.72; 95% CI, 0.56-0.94).

Previously, in June 2025, the FDA approved pembrolizumab in this indication based on the same results.5

References

1. Merck receives two positive EU CHMP opinions for KEYTRUDA® (pembrolizumab), for subcutaneous (SC) administration and for new indication for earlier-stage head and neck cancer. News release. Merck. September 19, 2025. Accessed September 19, 2025. https://tinyurl.com/mraxhjyc
2. Felip E, Rojas CI, Schenker M, et al. Subcutaneous versus intravenous pembrolizumab, in combination with chemotherapy, for treatment of metastatic non-small-cell lung cancer: the phase III 3475A-D77 trial. Ann Oncol. 2025;36(7):775-785. doi:10.1016/j.annonc.2025.03.012
3. FDA approves pembrolizumab and berahyaluronidase alfa-pmph for subcutaneous injection. Release. FDA. September 19, 2025. Accessed September 19, 2025. https://tinyurl.com/4ns5e8j7
4. Uppaluri R, Haddad RI, Tao Y, et al. Neoadjuvant and adjuvant pembrolizumab in locally advanced head and neck cancer. N Engl J Med. 2025;393(1):37-50. doi:10.1056/NEJMoa2415434
5. FDA approves neoadjuvant and adjuvant pembrolizumab for resectable locally advanced head and neck squamous cell carcinoma. News release. FDA. June 12, 2025. Accessed September 19, 2025. https://tinyurl.com/yt9p66xz