23andMe’s first-in-class anti-CD200R1 monoclonal antibody, 23ME-00610, by targeting CD200R1, offers a complementary approach to PD-1/PD-L1 blockade, potentially reversing immune suppression in the TME and enhancing T cell responses. 

The drug is currently being evaluated in a Phase I/II trial for its efficacy and safety in patients with advanced or metastatic clear-cell renal cell carcinoma. Preliminary clinical data, including efficacy data, for the clear-cell renal-cell carcinoma in the Phase IIa portion of its ongoing Phase I/IIa clinical trial evaluating 23ME-00610 were revealed for the first time as a poster presentation at the ESMO 2024.

Patients received 1400 mg given IV every 3 weeks until disease progression, unacceptable toxicity, or withdrawal from study. Patients received a median of three cycles of 23ME-00610, with three patients remaining on study by the April 1, 2024 data cutoff. 

Safety summary: 

• Nine of 10 patients reported adverse events in the ccRCC cohort.

• Three of 10 patients had treatment related AES all of which were either Grade 1 or 2. 

• Related AEs reported in this cohort included (one each): fatigue, nausea, vomiting, ALT increased, AST increased, dry mouth, headache, gastroesophageal reflux disease, and constipation and generally similar to the adverse events reported across the entire study.

• No high grade AES or AEs leading to discontinuation were reported.

• Across the entire study, two SAEs were reported as related by the investigators, including deep vein thrombosis (DVT) (G3) and diarrhea (G2).

In addition, preliminary baseline tumor analysis suggests that besides CD200 expression, higher vascularization may be associated with benefit from 23ME-00610 treatment.

Conclusion 

The treatment landscape for clear cell renal cell carcinoma (ccRCC) is highly competitive, with established therapies such as PD-1/PD-L1 inhibitors (e.g., OPDIVO and KEYTRUDA) and VEGF inhibitors (e.g., axitinib, cabozantinib) currently leading the market. Despite these options, many patients do not achieve long-term responses, highlighting a need for next-generation immunotherapies like 23ME-00610.

Results presented at ESMO 2024 indicated that 23ME-00610 is well-tolerated and safe at a dose of 1400 mg every three weeks in patients with clear cell renal cell carcinoma (ccRCC). The drug exhibited anti-tumor activity in those resistant to immunotherapy, maintaining a favorable safety profile, complete peripheral target engagement, and pharmacokinetics that support the every-three-weeks dosing schedule.

Given that patients with ccRCC often develop resistance to both ICIs and VEGF inhibitors, 23ME-00610 may serve as a valuable second-line or subsequent therapy, addressing an unmet need in this area. Future trials will be crucial in determining its optimal use and establishing its role in a competitive market. Other companies developing novel immunotherapies for ccRCC include AstraZeneca, Bristol-Myers Squibb, and Roche, which are all exploring next-generation ICIs, bispecific antibodies, and other immunomodulatory approaches.

For more insight into the patient's burden/epidemiology, treatment, and changing market landscape-related advancements, refer to the Renal Cell Carcinoma - Market Insight, Epidemiology and Market Forecast - 2032.