Is Two Better Than One? Anti-PD1/PDL1 Combination Therapies Take Centre Stage
By Jeffrey P Hodge, Vice President, Development Solutions, Oncology Center of Excellence, IQVIA Blog
There is an eagerness among stakeholders, including pharmaceutical companies, regulatory authorities and of course, patients, to see how a growing list of personalized medicines can help modernize the way varying cancers are treated. Shifting away from the reliance on chemotherapies and radiation treatments, we are at the point where immuno-oncology (IO), targeted and therapies associated with predictive biomarkers are increasingly becoming standard treatment.
In the U.S., since 2015, the landscape has expanded to include new precision medicine treatments targeting 24 different types of cancer, including difficult-to-treat cancers such as small cell lung cancer, Merkel cell carcinoma and urothelial carcinoma and several tissue-agnostic conditions. Within IO alone, there are more than 700 therapies currently in development across all phases. In particular, checkpoint inhibitors PD1/PDL1-targeted monoclonal antibodies or mAbs, which remain the most efficacious IO therapies, have increased. This includes the development of alternative subcutaneous and oral formulations. As the number of patients who are eligible to receive and respond to them have risen, the focus on this area of clinical care in cancer continues to see expansion. As such, keeping a close and constant eye on evolving clinical development trends for these mAbs is critical.
Since 2017, IQVIA has partnered with the Cancer Research Institute, a US non-profit cancer research organization, to pinpoint and analyze evolving global trends in PD1/PDL1 mAbs, highlighting how the treatment landscape is rapidly evolving and what is to come down the pike, offering hope to patients. To date, three joint analysis reports have been published in Nature Reviews Drug Discovery, including the latest trends findings shared in November 2020.
From the latest report, we know that these mAbs have received 67 approvals from the U.S. Food and Drug Administration (FDA) across 17 different cancer types and two tissue-agnostic conditions. But, more importantly, IQVIA and the Cancer Research Institute aimed to understand exactly how the inhibitors are studied and potentially why. Overall, findings show the industry has a strong interest in the potential of PD1/PDL1s in combination with other therapies, indicating a robust pipeline focused on anti-PD1/PDL1 combination treatment modalities may be building to help diversify options for patients in need.
A rise in PD1/PDL1 combination therapy
Since the first analysis of the PD1/PDL1 space three years ago, there has been a three-fold increase in total number of active clinical trials (3,674) examining these inhibitors. Making up 80 percent of the active trials, the largest growth in clinical development is concentrated in PD1/PDL1 mAbs in combination with other cancer therapies, including other IO therapies, targeted therapies, chemotherapies and radiotherapies. Over the last four years, chemotherapy continues to have a major impact as combination therapy with PD1/PDL1 mAbs for different tumor types, including non-small cell lung cancer, head and neck cancer and small-cell lung cancer. However, it is worth noting that in the first three quarters of 2020, VEGF/VEGFR-target therapies was the top combination therapy, surpassing chemotherapy by several trials.
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Diving deeper into PD1/PDL1 combination therapy trends
Adjuvant setting
Though other novel ways to treat cancer are gaining popularity (e.g., FGFR gene alternations, CAR-T therapies, etc.), global pharmaceutical companies are investing in evaluating PD1/PDL1 inhibitors in the adjuvant setting. This includes looking into therapies for major tumor types, including non-small cell lung cancer, melanoma, head and neck, bladder, breast and esophageal. With strong interest in this potential option, large Phase 3 trials are looking closely at possibilities to treat patients with PD1/PDL1 mAbs in adjuvant setting post-surgery, potentially catching disease earlier in progress.
As we look ahead, IQVIA relies on its advanced analytics and breadth of data insights to continually gauge how far PD1/PDL1 use in combination treatment falls within the adjuvant setting compared to metastatic cancer. Sponsors and researchers alike can look to these trends to better guide their clinical development strategies and shift focus to areas of greater benefit to patients, as appropriate.
Emergence of cancer vaccines
Based on the number of new trials started in the past year, PD1/PDL1 combination therapy with cancer vaccines is a notable area of interest for further examination. More than 20 PD1/PDL1 combination trials with cancer vaccines were initiated in 2020, even during the midst of the COVID-19 pandemic, as this combination strategy may maximize potential to improve clinical trial outcomes. Growing preclinical data show that combining vaccines and PD1/PDL1 inhibitors can initiate intensified immunogenicity and modulate the immunosuppressive tumor microenvironment.
In closely monitoring trends and providing updates in PD1/PDL1 inhibitor use and potential use, it is necessary to look into outside variables that affect the landscape such as global roadblocks like COVID-19. Examining trends over the first three quarters of 2020, the latest analysis of PD1/PDL1 inhibitor use also reported patient recruitment rates during COVID-19. In sponsors and clinical research organizations (CROs) working to maintain trials through COVID-19, analysis did show a drop in recruitment rates globally for both monotherapy and combination trials. However, combination trials in China actually increased by 18 percent, maybe due to the timing of the global pandemic and initial recovery in that country. It is safe to say that as COVID-19 vaccines are approved and in use around the world, there may be a noticeable recovery in enrollment in various regions. This is just another example of how trends in the oncology treatment space may evolve and affect sponsor and researcher decisions.
The innovative treatment approaches and uptake in use of PD1/PDL1 mAbs can be attributed to the increased focus on innovative trial designs that allow testing in combination and incorporation of precision biomarkers as well as greater flexibility in the number of enrolled patients and dose selection. It also helps that through advanced analytics and data insights, researchers are able to quickly identify safety risks and discontinue unsuccessful trials, shifting focus to other potential therapies and indications that could benefit patients.
As trends strengthen and change, it will be vital for sponsors and CRO experts to stay informed and develop and maintain agile strategies and adaptable approaches to ensure patient needs are better met and quicker.
To learn more, read Combinations take centre stage in PD1/PDL1 inhibitor clinical trials published in Nature Reviews Drug Discovery.
For information about oncology clinical trials, visit IQVIA.com/oncology