As we wrapped up the American Society of Clinical Oncology annual meeting last week, we renewed our commitment to advance global cancer care by integrating the patient’s perspective into our research and development efforts. Whether data presentations, clinical science symposiums or exhibit hall chatter, each day was packed with engaging conversations giving us the chance to explore the latest in R&D advancements and share our perspectives on how to better meet patient needs. 
 
There were many topics at ASCO 2023 worthy of review. We had special interest in the following updates coming out of the key stakeholder meeting. 
 
Building on Oncology Innovation 
Overall, ASCO 2023 showcased how community-wide exploration of disease pathways has provided a foundation for oncology R&D. A stronger understanding of how transformative therapeutics can be leveraged alone or in combination to extend indications and reach more patients was front and center at the meeting. 
 
For example, findings were announced from varying trials evaluating Merck’s PD-1 inhibitor Keytruda (pembrolizumab), which was first approved in the U.S. in 2014 for the treatment of patients with unresectable or metastatic melanoma, including: 
 

• When used with Moderna and Merck’s experimental cancer vaccine MRNA-4157 in a Phase 2b study, the combination reduced the risk of a deadly form of skin cancer spreading to other parts of the body or death by 65% in patients with stage 3 or 4 melanoma. 
• When used in combination with chemotherapy as a perioperative treatment regimen and solely in post-surgery in resectable stage 2, 3a or 3b non-small cell lung cancer, it reduced the risk of disease recurrence, progression or death by 42%, compared to chemotherapy and placebo. 
• When used in combination with chemotherapy, results of a phase 3 trial did not show statistically significant results, demonstrating a reduced risk of death by 16% compared to chemotherapy alone for patients with nonsquamous NSCLC. 

With an obvious need to increase early-stage cancer treatments, Novartis presented data indicating that Kisqali (ribociclib), its CDK4/6 inhibitor approved for advanced and metastatic breast cancer types, may be beneficial for early-stage breast cancer. Results from its Phase 3 NATALEE trial found that the treatment used alongside endocrine therapy as adjuvant therapy for patients with stage 2 or 3 HR+, HER2-breast cancer reduced risk for recurrence by 25% compared to patients solely on endocrine therapy after 34 months of follow-up. If continued studies show benefits, the treatment could extend in use for twice as many potential patients as its current indication. 
 
Broadening the Innovation Landscape 
ASCO always emphasizes trial results that may lead to improvements in clinical practice. Compared to previous meetings, this year there was a noticeable increase in the amount of data shared by sponsors, reflecting the rapid growth in cancer drug pipelines over the last few years.
 
Several results that are worth watching as a change in standard of care include: 
 

• Tumor-agnostic treatment approaches via antibody-drug conjugates and fibroblast growth factor receptor or FGFR inhibition:  

                       o   Janssen Pharmaceuticals’ Balversa (erdafitinib), initially approved for locally advanced or metastatic bladder cancer, showed potential for multiple FGFR-driven cancers regardless of tumor location or histology, including high-grade glioma, bile duct cancer and NSCLC and hard-to-treat malignancies, such as pancreatic cancer. 
                       o   AstraZeneca and Daiichi Sankyo’s HER2 ADC Enhertu (trastuzumab deruxtecan) decreased tumor growth in 37.1% of patients with various types of HER2-expressing solid tumors in the Phase 2 DESTINY-PanTumor02 trial presented at ASCO. 

• Delayed initiation of radiotherapy and chemotherapy and related toxicities for difficult-to-treat cancer: In the anticipated Phase 3 study for vorasidenib, a dual IDH1/2 inhibitor, findings showed that the treatment led to a 61% reduction in the risk of tumor progression or death compared to placebo for patients with grade 2 IDH1/2 mutated glioma. As such, the option may allow patients to delay the need for more aggressive therapies (e.g., chemotherapy) to avoid toxicities, which is especially noteworthy because patients with this malignant brain tumor are typically younger and can remain active with professional and personal activities.
• Stepping away from standard adjuvant chemotherapy approach for early-stage NSCLC: Among the multitude of data AstraZeneca presented at this year’s meeting, the results from its Phase 3 trial examining its once-daily oral treatment Tagrisso (osimertinib) showed improvement in survival rates by five years in patients with early-stage NSCLC. Working by inhibiting cellular growth of the EGFR gene, this treatment could become a new standard of care for these patients instead of chemotherapy. 
• Bispecific antibodies for relapsed or refractory multiple myeloma: Providing patients with another option beyond CAR-T therapies, Janssen announced results from its Phase 1b study of its first-in-class BCMAxCD3 bispecific antibody Techvayli (teclistamab-cqyv) in combination with first-in-class GPRC5DxCD3 bispecific antibody for patients with RRMM. Together, the treatments demonstrated high overall response rates of nearly 87% across all dose levels. In some cases, patients who were resistant to four prior lines of therapy showed response to this combination regimen, highlighting the need for additional treatment options for these patients while also considering quality of life. 
• Overall survival benefits in difficult-to-treat ovarian cancer: Showing why ADCs are becoming widely studied, Immunogen’s Elahere (mirvetuximab soravtansine-gynx) injection achieved a 35% reduction in risk of disease progression or death compared to varying chemotherapy in patients with folate receptor alpha-high, platinum-resistant ovarian cancer. It is the first novel treatment to demonstrate benefit in overall survival in this patient population in a Phase 3 study, showing the potential for patients to experience fewer serious side effects compared to standard chemotherapies used for this cancer type. 
• Continued movement of CAR-T to earlier lines of therapy: Both Janssen’s Carvykti (ciltacabtagene autoleucel), an autologous BCMA-directed CAR-T, and Kite Pharma’s Yescarta (axicabtagene ciloleucel), an autologous anti-CD19 CAR-T, came out on top when compared to standard of care in early refractory multiple myeloma and early relapsed/refractory large B-cell lymphoma, respectively. 

                          o   In Janssen’s global Phase 3 trial CARTITUDE-4, compared to the current physician’s choice in patients with lenalinomide-refractory multiple myeloma after one to three prior lines of therapy, Carvykti showed a significantly lower risk of disease progression or death. 
                          o   In Kite’s Phase 3 trial Zuma-7, patients who received Yescarta as second-line treatment for relapsed/refractory large B-cell lymphoma had a reduction in the risk of death and an improvement in overall survival when compared to current standard of care therapy. 
 
Further improvements through clinical trials 
ASCO 2023 highlighted how many new drugs and trials are entering clinics with new drug targets and related monotherapy and combination treatment regimen and new pathways. What was groundbreaking in drug development from just several years ago is rapidly becoming standard of care. 
 
As we look ahead, we know there is still much to achieve, especially in terms of ensuring that clinical trials are more accessible to all, including traditionally underserved populations, as well as alleviating drug supply roadblocks and conducting trials designed not only to improve traditional endpoints but also to enhance the quality of life for patients living with debilitating cancers. 
 
As a community, it is vital to keep all these goals in mind as we continue to build on our knowledge, expertise and experience to make a genuine impact in patients’ lives. 

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