AbbVie announced positive top-line results for telisotuzumab vedotin (Teliso-V) in 2L for lung cancer (Nsq mNSCLC)

On November 29^th, 2023, AbbVie announced positive top-line results from its P2 LUMINOSITY: telisotuzumab vedotin (Teliso-V) mono in 2L Nsq mNSCLC with c-Met+, including arms for both c-Met-int and c-Met-high.

AbbVie has previously publicly stated that they hope to move forward with these results to get accelerated approval.

Implications:

• Teliso-V is expected to directly compete with Trodelvy in 2L+ c-Met+ mNSCLC, a subset of Trodelvy’s addressable population in 2L+ mNSCLC.
  • The threat could be lower if Teliso-V is approved in only c-Met-high instead of c-Met+
  • AbbVie has stated that c-Met overexpression accounts for 37-67% of all mNSCLC (c-Met-high population unclear)
  • Teliso-V’s positioning reflects the broader trend where biomarker-driven competitors could carve away portions of Trodelvy’s market share over time
• Teliso-V’s efficacy is consistent with what was previously presented from P2 LUMINOSITY in c-Met-int, but the updated efficacy is quite lower in the c-Met-high population where Teliso-V would have been most competitive (ORR updated to 35% vs 52% previously in c-Met-high)
• Teliso-V’s safety profile was consistent with previous data. However, there are several notable AEs that could raise concern from physicians, including neuropathy, ocular AEs, anemia, metabolic AEs, and malignant neoplasm progression
• AbbVie recently announced in its Q3’23 Earnings that it would be seeking Accelerated Approval for Teliso-V in c-Met+ 2L mNSCLC. However, it is unclear whether the FDA would grant AA in c-Met+ or just in c-Met-high. It is also unclear whether the FDA would grant AA if Dato-DXd is approved in Nsq mNSCLC and Trodelvy presents positive data around the same time
  • Accelerated Approval Q4’24 (CI Estimate)
• Teliso-V was granted Breakthrough Designation by the FDA in 2022 in only c-Met-high 2L+ mNSCLC, and it currently has an ongoing P3 trial called TeliMET NSCLC-01: Teliso-V (c-MET+ ADC) mono in c-MET+ 2L Nsq la/mNSCLC w/ AGAs other than EGFR
  • TeliMET NSCLC-01 is set to read out by YE’24 (CI Estimate)

Detailed Results:

• Efficacy
  • P2 LUMINOSITY Initial Results (ASCO 2022)
    • ORR = 24% (c-Met-int)
    • ORR = 52% (c-Met-high)
  • P2 LUMINOSITY Updated Results (AbbVie PR 2023)
    • OS = 14.2mo (c-Met-int)
    • OS = 14.6mo (c-Met-high)
    • ORR = 23% (c-Met-int)
    • ORR = 35% (c-Met-high)
  • Notable Safety Profile
    • P2 LUMINOSITY Initial Results (ASCO 2022)
      • All-grade TEAEs: 96% (Gr3+ 48%)
      • Peripheral Neuropathy: 25% (Gr3+ 4%)
      • Ocular AEs: 18% (Gr3+ 1%)
      • Anemia: 14% (Gr3+ 2%)
      • Metabolic AEs: ~13% (Gr3+ 2%)
      • Diarrhea: 10% (Gr3+ 0%)
      • Malignant Neoplasm Progression: 10% (Gr3+ 8%)
      • Discontinuation Rate: 13%
    • No updated safety data was included in the press release, but AbbVie noted that the safety profile was consistent