Opinion: Nursing Considerations for Emerging CLDN6-Targeted Therapies
Understanding which patients may benefit from CLDN6-targeting immunotherapy and recognizing potential adverse effects is essential for oncology nurses.
Amanda Brink, DNP, APRN, FNP-BC, AOCNP
Oncology nurses regularly encounter new and emerging molecular targets that have the potential to expand treatment options and improve outcomes for patients. One such target gaining attention is claudin 6 (CLDN6), a protein that is normally present only during early development but can reappear in certain cancer cells, though largely absent in healthy adult tissues.
CLDN6 is most commonly found in cancers that arise from tissues where this protein is active during embryonic growth. It is highly expressed in testicular germ cell tumors, particularly embryonal carcinomas and yolk sac tumors, making these cancers prime candidates for CLDN6-targeted therapies. Similarly, certain ovarian germ cell tumors show elevated levels of CLDN6.1,2
Beyond germ cell tumors, a subset of epithelial ovarian cancers also demonstrates CLDN6 expression. Less frequently, CLDN6 has been detected in some non-small cell lung cancers and other solid tumors such as endometrial, gastric, and liver cancers.3
Because CLDN6 is largely absent in normal adult tissues, its selective presence in these malignancies makes it an attractive target for therapies designed to minimize harm to healthy cells. As a result, CLDN6 is an important focus for new treatments including bispecific antibodies, CAR T-cell therapies, and antibody-drug conjugates.1
With early-phase clinical trials underway targeting CLDN6, oncology nurses will increasingly support patients receiving these innovative therapies.
A CLDN6-targeting bispecific antibody yielded a 75% DCR in ovarian cancer in early testing.
Early Clinical Trial Results Show Promise for mRNA-Based Anti-CLDN6 Therapy
Recent data presented by Timothy Yap, MBBS, PhD, FRCP, at the American Society of Clinical Oncology 2025 Annual Meeting Yap discussed findings from a phase I/II trial (NCT05262530) testing BNT142, an mRNA therapy encoding the anti-CLDN6/CD3 bispecific antibody RiboMab02.1, in patients with advanced CLDN6-positive solid tumors. As of December 2, 2024, 65 patients, including those with ovarian, testicular, non-small cell lung, and rare cancers, received weekly intravenous doses across 7 dose levels.
Most patients were heavily pretreated, and safety was a primary focus. Treatment-related adverse events (TRAEs) occurred in 63% of patients, mostly mild to moderate. Common TRAEs included cytokine release syndrome (CRS) (22%), elevated liver enzymes (19%), and flu-like symptoms such as fever and chills (12%). Grade 3 or higher TRAEs occurred in 23%, with 2 dose-limiting toxicities: 1 grade 4 liver enzyme increase and 1 fatal instance of CRS.
Pharmacokinetic data showed dose-dependent production of the bispecific antibody with peak serum levels 24 to 72 hours after dosage. Transient increases in inflammatory cytokines indicated immune activation.
Efficacy was encouraging, with an overall disease control rate of 58% and higher responses at increased doses. In ovarian cancer, the disease control rate was 75%, including 7 partial responses, which is noteworthy given this cancer’s usual resistance to immunotherapy.
These early results demonstrate a manageable safety profile and promising anti-tumor activity, supporting further dose optimization and development of this mRNA-based bispecific antibody therapy.
Nursing Considerations
Nurses caring for patients receiving anti-CLDN6 therapies such as BNT142 play a vital role in monitoring and managing TRAEs, particularly cytokine release syndrome (CRS) and liver enzyme elevations. Early signs of CRS, including fever, chills, fatigue, low blood pressure, and shortness of breath, require prompt recognition and intervention. Regular monitoring of liver function is also essential, as elevated AST and ALT levels may signal liver toxicity. Nurses should be alert to symptoms of liver dysfunction and ensure timely reporting.
Premedications like antipyretics and antihistamines are often used to reduce the risk of infusion reactions; nurses should ensure these are administered as prescribed and help patients understand their purpose. With weekly intravenous infusions, nurses also guide patients in recognizing TRAEs and the importance of promptly reporting new or worsening symptoms.
Because these therapies stimulate the immune system, patients may develop flu-like symptoms that require supportive care. Emotional support and clear communication can help reduce anxiety associated with investigational treatments. Finally, nurses play a key role in interdisciplinary coordination, ensuring that TRAEs are reported swiftly to facilitate appropriate dose adjustments and maintain patient safety. For eligible patients, oncology nurses can also assist in identifying clinical trial sites that offer access to anti-CLDN6 therapies.
References
- Richardson NH, Adra N. Novel therapeutics in refractory germ cell tumors. Curr Opin Oncol. 2025;37(3):267-273. doi:10.1097/CCO.0000000000001129
- Mackensen A, Haanen JBAG, Koenecke C, et al. CLDN6-specific CAR-T cells plus amplifying RNA vaccine in relapsed or refractory solid tumors: the phase 1 BNT211-01 trial. Nat Med. 2023;29(11):2844-2853. doi:10.1038/s41591-023-02612-0
- Yap TA, Slama J, Tolkach Y, et al. First-in-human phase I/II trial evaluating BNT142, a first-in-class mRNA encoded, bispecific antibody targeting claudin 6 (CLDN6) and CD3, in patients with CLDN6-positive advanced solid tumors. J Clin Oncol. 2025;43(16_suppl):2501. doi:10.1200/JCO.2025.43.16_suppl.2501
