Are there any clinical trials at an advanced stage for B7H3 (B7 homolog 3) solid tumor treatments?

Advanced Stage Clinical Trials for B7H3-Targeted Solid Tumor Treatments

Currently, there are several promising B7H3-targeted therapies in advanced clinical trial stages for solid tumors, with YL201 (a B7H3-targeting antibody-drug conjugate) having completed a large-scale phase 1/1b trial with 312 patients and already advancing to phase 3 trials for small cell lung cancer and nasopharyngeal carcinoma. 1

Current Advanced-Stage Clinical Trials

Antibody-Drug Conjugates (ADCs)

• YL201: The most advanced B7H3-targeting therapy in clinical development
  • Phase 1/1b trial completed with 312 patients across multiple solid tumor types
  • Demonstrated encouraging efficacy:
    • 63.9% objective response rate (ORR) in extensive-stage small cell lung cancer
    • 48.6% ORR in nasopharyngeal carcinoma
    • 28.6% ORR in lung adenocarcinoma
    • 54.2% ORR in lymphoepithelioma-like carcinoma
  • Phase 3 trials already initiated for SCLC and NPC (ClinicalTrials.gov identifiers: NCT05434234 and NCT06057922) 1
  • Acceptable safety profile with manageable adverse events

Bispecific Antibodies

• Anti-B7H3 × Anti-CD3 bispecific antibodies: These have shown potent cytotoxic activities against B7H3-positive tumor cell lines in preclinical studies and are advancing to clinical trials 2
• Omburtamab: A radiolabeled monoclonal antibody targeting B7H3 mentioned in clinical guidelines for certain embryonal brain tumors 3

CAR-T Cell Therapies

• B7H3 CAR-T cells: Currently in phase I clinical trials
  • STRIvE-02 trial (NCT04483778): First-in-human phase I study with 16 patients enrolled
  • Demonstrated tolerability and limited antitumor activity
  • One patient achieved partial response after second CAR-T infusion 4
  • Ongoing development to improve efficacy for solid tumors 5, 6

Efficacy and Safety Profiles

Efficacy

• B7H3-targeted ADCs like YL201 show the most promising efficacy to date, particularly in:

  • Small cell lung cancer
  • Nasopharyngeal carcinoma
  • Lymphoepithelioma-like carcinoma 1

• CAR-T approaches targeting B7H3 have demonstrated:

  • Limited but measurable clinical responses in early trials
  • Need for higher levels of CAR-T cell expansion to achieve objective responses 4
  • Potential for improved efficacy with novel modifications 5

Safety

• YL201 ADC safety profile:

  • Most common grade 3+ adverse events: neutropenia (31.7%), leukopenia (29.5%), anemia (25.0%)
  • Low incidence of interstitial lung disease (1.3%) and infusion reactions (0.3%) 1

• B7H3 CAR-T safety profile:

  • Generally tolerable without acute on-target, off-tumor toxicity
  • Cytokine release syndrome and transaminitis observed with higher expansion 4
  • Safety advantage due to lower expression on normal tissues compared to tumor tissues 6

Tumor Types Most Responsive to B7H3-Targeted Therapies

Based on current clinical evidence, the following tumor types appear most responsive to B7H3-targeted therapies:

1. Small cell lung cancer (63.9% ORR with YL201)
2. Lymphoepithelioma-like carcinoma (54.2% ORR)
3. Nasopharyngeal carcinoma (48.6% ORR)
4. Lung adenocarcinoma (28.6% ORR) 1

Additionally, preclinical studies suggest potential efficacy in:

• Pediatric solid tumors (osteosarcoma, Ewing sarcoma)
• Brain tumors (medulloblastoma)
• Pineal parenchymal tumors 3, 6

Future Directions

• Phase 3 trials of YL201 are already underway for SCLC and NPC 1
• Ongoing development of B7H3 CAR-T approaches with:
  • Novel modifications to improve persistence
  • Local delivery routes to enhance efficacy
  • Combination with standard therapies 5
• Exploration of B7H3-targeted bispecific antibodies in clinical settings 2
• Potential for combination approaches with checkpoint inhibitors or other immunotherapies

Clinical Implications

B7H3 represents a promising target for solid tumor therapy due to its:

1. Overexpression across multiple solid tumor types
2. Limited expression on normal tissues
3. Role in tumor progression and immune evasion

The most advanced B7H3-targeted therapy (YL201 ADC) has already demonstrated significant clinical activity and is progressing to phase 3 trials, making it the most promising near-term option for patients with B7H3-expressing solid tumors, particularly SCLC and NPC.