As the 2024 American Society of Clinical Oncology (ASCO) annual meeting approaches, excitement builds over the latest in cancer treatment advancements. From May 31 to June 4, industry leaders will unveil new data on different therapies. Leading pharmaceutical companies, including AbbVie, Gilead Sciences, Johnson & Johnson, Bristol Myers Squibb, Dizal Pharmaceutical, AstraZeneca, and others are prepared to unveil the eagerly anticipated results as ASCO 2024 draws to a close, and are looking at this opportunity to present their innovations in lung cancer.

There will be an array of impactful data in NSCLC. The 2024 ASCO annual meeting promises to be a pivotal conference for advancements in lung cancer management, with numerous studies likely to influence and change clinical practices.

1. Abstract Number - 8513

Title – Dizal Pharmaceuticals to present sunvozertinib’s WU-KONG1 Part B study results: Transforming NSCLC treatment with global breakthroughs as first oral drug in EGFR Exon20ins therapy

Commentary – Sunvozertinib's clinical success and international regulatory advancements position it as a groundbreaking treatment for NSCLC with EGFR exon20ins mutations.

Executive Summary – Sunvozertinib, an oral medication for NSCLC with EGFR exon20ins mutations, has shown transformative potential in clinical trials. Key data from the WU-KONG1 Part B study will be presented at ASCO, following successful results and approval in China. Dizal Pharmaceuticals is accelerating its NDA submission with global regulatory agencies.

Main content - Sunvozertinib, when used as a single oral medication to treat patients with NSCLC with EGFR exon20ins mutations, has been shown in numerous clinical trials to have transformative potential. Primary analysis data of sunvozertinib will be presented at the upcoming ASCO conference, highlighting the topline results from its WU-KONG1 Part B study (NCT03974022; ≥ 2nd line).In August 2023, sunvozertinib was approved in China, making it the first oral drug ever developed for the treatment of patients with EGFR exon20ins mutations in lung cancer. The approval was for the treatment of patients who progressed on first-line treatment. The approval in China was supported by results from the phase II WU-KONG6 study (NCT05712902; CTR20211009) in which the agent led to a confirmed ORR of 60.8%.

WU-KONG1 Part B global pivotal Phase II trial aims to determine the safety and efficacy of sunvozertinib in treating patients with EGFR exon20ins mutation-positive NSCLC who have relapsed or are refractory to treatment. This study includes patients from North America, South America, Europe, and Asia. The primary analysis showed that sunvozertinib demonstrated promising antitumor efficacy in relapsed or refractory NSCLC with EGFR exon20ins, with a tolerable safety profile. Similar findings to the WU-KONG6 investigation were seen in the preliminary analysis. With Breakthrough Therapy Designation, Dizal Pharmaceuticals is working closely with the US FDA, EMA, and other regulatory agencies to accelerate its NDA submission. 

Conclusion: Sunvozertinib has shown significant promise in treating NSCLC with EGFR exon20ins mutations, gaining approval in China and progressing through global trials. The upcoming ASCO presentation of WU-KONG1 Part B data and ongoing regulatory collaborations highlight its potential as a transformative therapy. 

Abstract Number – 103

Title – AbbVie is gearing up to unveil the primary analysis of the LUMINOSITY trial showcasing telisotuzumab vedotin’s role in EGFR wild-type NSCLC

Commentary – AbbVie's presentation of telisotuzumab vedotin's primary analysis at ASCO holds promise for NSCLC patients with c-Met overexpression, offering potential breakthroughs in survival outcomes and safety. Their focused approach to targeting EGFR wild-type NSCLC sets them apart in the field of c-Met medications.

Executive Summary – LUMINOSITY study's primary analysis on telisotuzumab vedotin, a first-in-class c-Met protein-directed antibody-drug conjugate, at ASCO, holds the potential to address the poor prognosis of NSCLC patients with c-Met overexpression. With promising survival outcomes, the focus shifts to the therapy's safety profile, crucial for its clinical applicability.

Main Content – With telisotuzumab vedotin, AbbVie is focusing on NSCLC patients with c-Met overexpression. c-Met is a tyrosine kinase receptor that is commonly overexpressed in many solid tumors and is present in approximately 25% of patients with advanced EGFR wild-type NSCLC. Currently, patients with c-Met overexpression have poor prognosis. Telisotuzumab vedotin is a first-in-class, c-Met protein–directed antibody-drug conjugate under study in several settings. The primary analysis of the LUMINOSITY clinical study is scheduled to be presented by AbbVie at ASCO 2024.

AbbVie released LUMINOSITY trial updated findings in November 2023. These results revealed that the median overall survival for c-MET high and c-MET intermediate patients was 14.6 months and 14.2 months, respectively, with a duration of response of 9 months and 7.2 months. This update showed that the drug fell short from its earlier analysis, also provided some insight into the possibility of an accelerated approval path. There are several major safety concerns with this medication. The initial analysis of LUMINOSITY presented at AACR 2021 showed adverse events that were possibly related to treatment with telisotuzumab vedotin and led to death in three patients. Pneumonia and bronchopulmonary bleeding were among the Grade 5 adverse events reported in a previous Phase II research.

What level of data company plans to present at ASCO 2024 will be intriguing to watch. If telisotuzumab vedotin continues to be tolerable, that is to be expected, AbbVie's development program stands apart from other c-MET medications.

Conclusion: Targeting c-Met overexpression with treatments has the potential to affect a wide range of patients, since it might arise as a secondary vulnerability following treatment with TKIs or appear de novo in people who have not received any treatment. With promising survival outcomes and a focus on EGFR wild-type NSCLC, AbbVie's development program stands out from other c-Met medications. The upcoming presentation at ASCO is all set to release the primary analysis results. There is an opportunity to take this data to the health authorities to discuss potential for accelerated approval. If and when Teliso-V gets approved and comes to market, the ADC would become the first drug approved for use in this patient population (i.e., c-Met overexpression). 

Abstract Number – LBA8500

Title – Insights from the TRODELVY’s EVOKE-01 trial where it showed numerically positive trend, but statistically non-significance

Commentary – After falling short in Phase III EVOKE-01 study’s primary endpoint in metastatic NSCLC, Gilead will showcase the detailed analysis of the curves and subset data at the 2024 ASCO. The upcoming ASCO meeting will shed light on how this antibody-drug conjugate can enhance NSCLC treatment strategies.

Executive Summary – The Phase III EVOKE-01 trial compares TRODELVY to docetaxel in metastatic NSCLC patients with post-platinum-based treatment plus checkpoint inhibitor, showing a survival advantage for the former, especially in squamous and nonsquamous histologies. Insights from this study will inform the integration of sacituzumab govitecan into NSCLC treatment paradigms and advance the broader TROP-2 ADC class, impacting Gilead's development strategy in NSCLC.

Main Content – TRODELVY (sacituzumab govitecan-hziy) vs. docetaxel is the TROP-2–targeted antibody-drug combination being evaluated in EVOKE-01 for patients with metastatic or advanced NSCLC with disease progression during or following platinum-based treatment plus a checkpoint inhibitor. Although the study did not meet its primary endpoint of overall survival with sacituzumab govitecan, a numerical improvement in overall survival favoring this ADC over docetaxel was observed, particularly for patients with both squamous and nonsquamous disease histologies. 

Consequently, comprehending how this medication can be more effectively included in NSCLC treatment regimens will require a thorough review of the curves and subset data that will be given at the ASCO meeting. The larger TROP-2 ADC class and Gilead's development plan for sacituzumab govitecan in NSCLC should benefit from the trial's findings.

Conclusion: Despite significant advancements with immune checkpoint inhibitors (ICIs) in treating NSCLC, challenges persist, particularly with disease progression after the first year of treatment. This underscores the unmet need, especially for patients who have progressed on prior ICI therapy. TROP2 has emerged as a pivotal target in NSCLC treatment, yet leading TROP2 antibody-drug conjugates (ADCs) in trials for second-line and beyond treatments have shown suboptimal outcomes, prompting further investigation. Another anti-TROP2 ADC, datopotamab deruxtecan (Dato-dxd) from AstraZeneca/Daiichi Sankyo exhibited disappointing results in the TROPION-Lung01 trial. Currently, Sacituzumab govitecan is undergoing late-phase trials for first-line NSCLC treatment in combination with ICIs with or without chemotherapy. Success in these trials could revolutionize first-line NSCLC treatment, influencing patient care and drug development strategies in subsequent treatment lines.

Abstract Number – LBA8007

Title – CheckMate 77T unveils perioperative immunotherapy breakthrough in NSCLC, enhancing survival

Commentary – The utilization of PD-1/L1 inhibitors both pre and post-surgery for early-stage NSCLC holds significant importance. CheckMate-77T trial could offer valuable insights into this matter, potentially clarifying uncertainties surrounding this approach.

Executive Summary – Administering nivolumab as part of a perioperative treatment plan holds promise in lowering the chances of disease recurrence and enhancing overall clinical outcomes for individuals with resectable NSCLC.

Main Content – Data is anticipated from the Phase III CheckMate 77T trial (NCT04025879), which looked into perioperative chemotherapy immunotherapy in patients with early-stage, resectable NSCLC. Interim analysis showcased that the addition of perioperative nivolumab to neoadjuvant chemotherapy increased event-free survival in patients with resectable NSCLC. Bristol Myers Squibb is prepared to present the Phase III CheckMate 77T study data at the ASCO meeting. The trial will provide light on the possible advantages of using immunotherapy for NSCLC patients during their perioperative period. This work reinforces the neoadjuvant chemotherapy treatment that is the standard of care and provides evidence in favor of perioperative nivolumab as a useful strategy for lowering the risk of lung cancer relapse.

Conclusion: The use of immune checkpoint blockade either before or around the time of surgery has profoundly transformed the management of early-stage NSCLC. Bristol Myers Squibb OPDIVO appear competitive to rival Merck's KEYTRUDA in the pursuit of dominance in early-stage NSCLC treatment. The Phase III CheckMate 77T trial indicates that adding perioperative nivolumab to neoadjuvant chemotherapy enhances event-free survival in patients with resectable early-stage NSCLC. 

Abstract Number – LBA8505

Title – Turning the Tide: Subcutaneous Amivantamab could be better that IV Amivantamab potentially reducing Infusion-Related Reactions

Commentary – PALOMA-3 presentation of subcutaneous amivantamab and lazertinib showcasing cutting-edge approaches in lung cancer. Given amivantamab's unique mechanism targeting EGFR and MET, along with its previous accelerated approval for EGFR exon 20 insertion mutations, this trial's findings could significantly impact treatment approaches. 

Executive Summary – By lowering infusion-related reactions could position subcutaneous amivantamab as a competitor to TAGRISSO, a status that RYBREVANT (IV Amivantamab) currently does not hold. 

Main Content – 

The Phase III PALOMA-3 trial results at ASCO are much awaited, as they will provide valuable insights into the efficacy of subcutaneous vs. intravenous amivantamab in combination with lazertinib for NSCLC patients with specific EGFR mutations. During Phase III MARIPOSA, combining IV amivantamab with lazertinib led to infusion-related reactions in approximately 63% of patients, with 6% being severe (Grade 3+). This resulted in IV amivantamab being perceived as significantly less safe compared to TAGRISSO. Introducing a subcutaneous form of amivantamab could potentially decrease infusion-related reactions and enhance safety overall. If this alternative maintains similar effectiveness, physicians might be more inclined to consider this regimen instead of opting for TAGRISSO.

In addition PALOMA-3 trial, data from the Phase II PALOMA-2 trial, assessing the use of subcutaneous amivantamab with lazertinib as first-line therapy for advanced NSCLC patients with EGFR ex19del or L858R mutations, is also set to be revealed at ASCO 2024 (Poster Abstract #LBA8612). Furthermore, ASCO 2024 will feature the presentation of two additional abstracts from RYBREVANT.

• Subgroup analysis from the landmark Phase 3 MARIPOSA study evaluating first-line treatment with RYBREVANT (amivantamab-vmjw) and lazertinib in patients exhibiting high-risk clinical and biological features commonly observed in EGFR-mutant advanced NSCLC, who typically experience poorer outcomes (Oral Abstract #8504)

• Results from Cohort C of the CHRYSALIS-2 study evaluating RYBREVANT plus lazertinib in patients with atypical EGFR-mutant advanced NSCLC who were treatment-naïve or received two or fewer prior lines of treatment (Oral Abstract #8516)

Conclusion: Amivantamab is a fully human bispecific antibody targeting EGFR and MET with immune cell-directing activity. It received accelerated approval from the US FDA in May 2021 for the treatment of adult patients with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations. Recently, in March 2024, the US FDA approved amivantamab- in combination with chemotherapy for first-line treatment of patients with NSCLC with EGFR Exon20ins mutations. This FDA action converts the May 2021 accelerated approval to a full approval based on the confirmatory Phase III PAPILLON study. A subcutaneous formulation of amivantamab could reduce infusion-related reactions and improve overall safety. It is anticipated that meaningfully reduced infusion-related reactions could make subcutaneous amivantamab the competitor of TAGRISSO.