Does Your Immunooncology Program Need Dako 22C3 or Ventana SP263? CGI Runs All Four PD-L1 IHC Clones. Let’s Find Out Which Works Best For You.

Written by: JamieThalmann

Published on:
July 5th, 2016

PD-L and PD-L1 inhibitors will continue leading the paradigm shift in oncology toward immunotherapy for the foreseeable future. The PD-L1 IHC assays that have been developed as therapeutically paired diagnostics are now being pressed into service for hundreds of new combination treatments and indication expansions.

Currently, four unique clones have reached clinical practice across Agilent’s Dako and Roche’s Ventana platforms. Cancer Genetics was recently publicized as a certified provider of PD-L1 IHC, Ventana SP142 for Roche’s TECENTRIQ (atezolizumab) approved in bladder cancer. This completed our portfolio of FDA approved complementary and companion diagnostics, which already included Dako 28-8 PharmDx for OPDIVO® (nivolumab) in NSCLC, as well as Dako 22C3 PharmDx for KEYTRUDA® (pembrolizumab) in NSCLC and melanoma. We have the final PD-L1 clone currently available on the market, Ventana SP263 for durvalumab, in late-stage development for FDA approval.

Specific technical differences exist between these four antibodies that may impact efficacy for any given clinical program. Most fundamentally, 28-8, SP142, and SP263 are rabbit mAbs, while the Dako 22C3 is derived from mouse. Roche’s SP142 is unique in that it marks epitopes within the intra-cellular domain, while the other three have extra-cellular targets. Additionally, SP142 has a more complex scoring method combining independent tumor cell and immune cell percentages and intensities. Thresholds for calling vary across each clone (Fig.1.). The result of this is that the highly specialized expertise developed by our group medical director Rita Shaknovich, MD, Ph.D. and the pathology team are critical to maintaining assay performance and fidelity across platforms, clones, and indications.

PD-L1 Color Table

There is evidence starting to accumulate that while these diagnostics are reliant on subjective calls from pathologists there may be a time in the near future when they can be used interchangeably. AstraZeneca recently published the results of a large multi-site study indicating over 90% concordance between three of the antibodies in NSCLC. Maintaining a technology-agnostic approach to diagnostic platforms allows us to be a consultative partner on which PD-L1 platform will best fit any given study. This exceptional composition of proficiencies and flexibility has positioned us to be the laboratory of choice for immunooncology clinical trials as well as intra- and inter-laboratory validation studies for leading diagnostic platform companies.

We have navigated indications as diverse as glioblastoma, CRC, melanoma, NSCLC, MI/NMI bladder cancer, multiple myeloma, and Non-Hodgkin lymphoma. Our cross-platform competencies have allowed us to recently expand our role in ALCHEMIST to include Dako PD-L1 IHC 28-8 pharmDx, in response to the NCI’s inclusion of a fourth clinical trial evaluating nivolumab.

As biomarker testing continues to evolve in response to technological innovation, CGI will be there on the leading edge. Look for our upcoming work on immunotherapy biomarkers such as CTLA4 by flow cytometry.