ASCO 2024 – Lung Cancer Research Takeaways

By Renee Botello MSc, Navigator, Treatment and Trials, GO2 for Lung Cancer 

“[In the past] walking through ASCO, you were hard pressed to find anybody working in lung cancer, and now you’re hard pressed on finding somebody who is not working in lung cancer” – Danielle Hicks, Chief Patient Officer at Best of ASCO 2024 Living Room

Lung cancer was a hot topic at the 2024 ASCO meeting. The depth and breadth of the studies presented allow us to appreciate the ever-changing treatment practices and approaches to care in the lung cancer space. The GO2 team was onsite to learn about breakthroughs in lung cancer research to bring back to our community.   

Small cell lung cancer (SCLC) 

• ADRIATIC trial resulted in positive data for treating limited-stage SCLC, and further research is still underway. In the trial, Imfinzi (durvalumab) showed considerable improvement in overall survival and progression-free survival compared to placebo in patients who did not progress on chemoradiation.   

• DeLLphi-301 phase 2 study showed promising data on the efficacy and benefit of Imdelltra (tarlatamab) for previously treated and brain stable SCLC patients. This follows the fast-tracked FDA approval of Imdelltra (tarlatamab) earlier this year.    

Non-small cell lung cancer (NSCLC) 

• EGFR 
  • LAURA trial
    This trial is pushing for a change in the standard of care treatment (widely agreed upon/accepted treatment) for unresectable EGFR+ stage 3 (III) NSCLC. Tagrisso (osimertinib) showed a promising increase in progression-free survival vs. the placebo after chemoradiation.   
  • CHRYSALIS-2 trial
    The combination of amivantamab and azertinib demonstrated clinically meaningful antitumor activity in patients who had progressed on previous treatment for advanced EGFR+ NSCLC. The results of the combination also indicate an effective response for active CNS metastases while also showing improved progression-free survival in patients with high-risk biomarkers, representing a promising change in the standard of care for treatment naïve (untreated) EGFR+ advanced NSCLC.
  • HARMONi-A, phase 3
    Results showed a promising improvement in progression-free survival when combining AK112 (ivonescimab) and chemotherapy in patients who had progressed on treatment with EGFR TKIs. This may represent a new treatment option for EGFR+ lung cancer.   

• ALK+ 
  • CROWN study
    This study presented 5-year data that, to this date, noted the longest treatment outcome for advanced-stage NSCLC, with 60% of participants having progression-free survival. This study looked at the comparison of two ALK inhibitors, lorlatinib vs. crizotinib), in ALK+ NSCLC. Data showed a continued 5-year benefit with lorlatinib. This is an unprecedented outcome in the treatment setting and a new benchmark in targeted therapy for lung cancer.
  • ALINA trial, phase 3 
    Results demonstrated a considerable improvement in health-related quality of life for adjuvant (given after the primary treatment) alectinib vs. chemotherapy in patients with ALK+ NSCLC that has been resected (partial or full tumor removal). With previous disease-free survival results in the study, alectinib may be a promising consideration for adjuvant treatment for ALK+ NSCLC patients.

• KRAS 
  • KRYSTAL-12 trials
    There were promising results in progression-free survival and overall response of Krazati (adagrasib) over the chemotherapy docetaxelin KRAS G12C NSCLC patients who had previously received platinum-based chemo with PD-L1 treatment. 
  • CodeBreak 202
    From the CodeBreak 101 study, sotorasib, a KRAS G12C-targeted TKI, in combination with chemotherapy, showed preliminary antitumor activity as a first-line treatment for PD-L1 negative NSCLC patients. Based on the responses of the CodeBreak 101 study, the combination of sotorasib and chemotherapy for negative PD-L1 KRAS G12C NSCLC will continue to be evaluated in the CodeBreak 202 global phase 3 study, which is currently recruiting.
  • SUNRAY-01
    From the LOXO-RAS-20001 phase 1/2 study, Lynparza (olomorasib), in combination with pembrolizumab, demonstrated preliminary efficacy for KRAS G12C NSCLC. Lynparza (olomorasib) is a potent and highly selective inhibitor of KRAS G12C, and Keytruda (pembrolizumab) is a type of immunotherapy approved for KRAS G12C NSCLC. The combination of Lynparza (olomorasib) with Keytruda (pembrolizumab) or Keytruda (pembrolizumab)  with chemo in 1L NSCLC is being tested in the SUNRAY-01 study. This study aims to further investigate the potential combinations and targeted treatment approaches to this type of mutation in NSCLC.    

• ROS1 
  • TRUST-I trial, phase 2
    Taletrectinib (DS-6051b) yielded a durable response in TKI naïve, pretreated ROS1+ NSCLC. Talectrectinib (DS-6051b) demonstrated activity against resistance mutations in treatment, and possible new drug applications may be considered for locally advanced or metastatic NSCLC. 
  • Multicenter, open-label, phase 2 trial
    Lorlatinib, a potent, brain-penetrant ROS1 TKI, demonstrated durable clinical results in TKI naïve (never been treated with a TKI), advanced ROS1+ NSCLC. This includes participants with central nervous system metastases. These results open the possibility for an earlier stage treatment for ROS1+ NSCLC.    

• HER2 
  • Beamion LUNG-1, phase 1a/1b
    A HER2-specific TKI, BI 1810631 (zongertinib), showed promising efficacy in patients with HER2+ NSCLC. This opens the door to treating HER2-specific NSCLC, more personalized lung cancer treatment, and broader biomarker testing requirements.
  • CheckMate 9LA
    A 5-year follow-up was provided on the combination of Opdivo (nivolumab), Yervoy (ipilimumab), and chemotherapy as first-line treatment for metastatic NSCLC. Results of the study showed improved progression-free survival and maintained benefit in 5 years over chemotherapy alone, particularly in tumors with low PD-L1 expression (<1%) or squamous histology. This provides a promising option for metastatic NSCLC with PD-L1 considerations. 

• ADCs (antibody-drug conjugates) 
  • ICARUS-LUNG01, phase 2
    Based on ICARUS-LUNG01, phase 2 results in heavily treated advanced NSCLC, DATO-DXD (datopotamab deruxtecan, an ADC) demonstrated promising improvement in progression-free survival over docetaxel (chemotherapy). These efficacy and safety results are similar to those reported in the TROPION-Lung01 study, with non-squamous participants benefiting the most from the ADC.
  • EVOKE-01, phase 3
    In the study, TROP-2-targeted ADC Trodelvy (sacituzumab govitecan-hziy) was studied in comparison to chemotherapy (docetaxel) in patients with advanced or metastatic NSCLC who have progressed on previous treatment. Although the study’s primary endpoints were not met, there was an improvement in numbers with the overall survival in the ADC arm, moving the research to better understand how to approach this treatment for NSCLC that has progressed on or after platinum-based chemotherapy and checkpoint inhibitors.    

Improving quality of life 

• Cancer treatment at all ages
  Research at ASCO recognized the significance of the increasing cases among young adults diagnosed with lung cancer and the unique considerations specific to this age of diagnosis. From the risk factors to the specific questions posed by the increasing amount of diagnoses in this age group (under 50 years), there is a growing interest in understanding all the aspects of the lung cancer experience and improving treatment outlooks for all lung cancer patients. 
• Accessible cancer care
  Researchers presented on high-quality, accessible palliative care, including the PALOMA-3 trial and its study of efficacy and safety in different Rybrevant (amivantamab) and Leclaza (lazertinib) administration methods. The study’s results show promising outcomes in medication administration, with injections not being less effective than IVs. This opens the door for discussing how to best approach treatment based on each patient. From vaccines to the type of drug administration method, the multidisciplinary care approach observed within the ASCO research pushes towards empowering lung cancer care and treatment outcomes.

Promising new advances for future treatment and cancer care

Researchers continue to study the different areas of lung cancer treatment and care. A notable research landscape around lung cancer was presented at ASCO, with continued strides towards treating it in a more personalized manner. From biomarker testing to combination therapies allowing for more personalized treatment, research at ASCO focused on paving the way for a new horizon in lung cancer treatment and care.