Experts Highlight Top Findings From the 2024 IASLC World Conference on Lung Cancer

Alexander Spira, MD, PhD, FACP

From practice-changing research to new agents coming down the pike, lung cancer experts sat down with OncLive® to provide the most notable takeaways from the 2024 IASLC World Conference on Lung Cancer in a series of interviews. In case you missed any of the meeting’s key sessions, check out these insights below from the following lung cancer specialists:

• Alexander Spira, MD, PhD, FACP, Virginia Cancer Specialists; The US Oncology Network
• Li Zhang, professor, Sun Yat-sen University Cancer Center
• T. Jeroen N. Hiltermann, MD, University of Groningen
• Natasha B Leighl, BSc, MMSc, MD, Princess Margaret Cancer Centre
• Tina Cascone, MD, PhD, The University of Texas MD Anderson Cancer Center
• Triparna Sen, PhD, Icahn School of Medicine at Mount Sinai
• Andrea Wolf, MD, Mount Sinai Hospital
• Amanda Herrmann, MD, PhD, University of California, San Diego, School of Medicine
• Jacob Sands, MD, Dana-Farber Cancer Institute; Harvard Medical School
• Upal Basu Roy, PhD, MPH, LUNGevity Foundation
• John Heymach, MD, PhD, The University of Texas MD Anderson Cancer Center
• Marina Chiara Garassino, MD, University of Chicago Medicine
• Xiuning Le, MD, PhD, The University of Texas MD Anderson Cancer
• Sally Lau, MD, Perlmutter Cancer Center, NYU Langone Health
• Bellinda King-Kallimanis, PhD, LUNGevity Foundation

The Phase 3 HARMONi-2 Trial (AK112-303; NCT05499390) Bolsters Excitement for Ivonescimab (AK112) in Non–Small Cell Lung Cancer (NSCLC)

Spira: Ivonescimab is an interesting drug. It's a PD-L1/VEGF bispecific and we're all a bit surprised because in the PD-L1–high population, preliminary data showed that it was better [than pembrolizumab (Keytruda)]. VEGF [agents] have been around for quite some time, and we just haven't seen a lot of good information about it, so this agent took us by surprise. These updated data [from HARMONi-2] will change the paradigm for patients with a high PD-L1 score.

Unfortunately, this study would have to be completely replicated in the United States, which investigators are starting to do. We're a ways away from getting this drug to patients, but it's very exciting right now.

Zhang: HARMONi-2 is the first trial to show that [ivonescimab produced better efficacy outcomes] than single-agent [pembrolizumab] in the wild-type population of patients with NSCLC. However, no overall survival [OS] data were available, but I think it is there. [Regarding] next steps, we will see global studies [employing] the same design [of HARMONi-2] with the bispecific antibody vs pembrolizumab. Hopefully, this drug will be available in the future.

Hiltermann: I found these results compelling. It's, of course, a Chinese study, and needs to be repeated in Europe, America, and other countries. I wouldn't be surprised if ivonescimab could even outperform [its prior efficacy from HARMONi-2 through future global studies], because more patients in Europe tend to harbor TP53 mutations in lung cancer, and that's one of the targets that VEGF [is directed towards]. I found it a to be very interesting study.

Leighl: As a Canadian, whenever we add a VEGF inhibitor [to standard therapy] we always see better progression-free survival [PFS], but not OS. However, for the first time, I'm hopeful that this may change, and we can move beyond PD-1 monotherapy for patients with PD-L1–high NSCLC, and hopefully, without a lot of extra toxicity.

Cascone: I was fortunate to be the discussant of a small-scale phase 2 study [NCT04736823] [evaluating] perioperative ivonescimab in China. Here, we saw encouraging, numerically higher pathologic complete response [pCR] rates with ivonescimab plus chemotherapy followed by surgery and ivonescimab.

It will be important to understand more about the patient characteristics in the subgroup of patients that experience most of the benefit from this combination, as well as the safety that is relevant to the inhibition of the VEGF pathway. It's exciting to see a chemotherapy-sparing regimen that is impacting PFS and additional outcomes with safety. I [look forward to] seeing how this compound can move forward in clinical testing.

Rethinking Adjuvant and Neoadjuvant Immunotherapy Approaches

Sen: This meeting brings together the various aspects of NSCLC [management]. In NSCLC, there are [several] newer immunotherapy targets [emerging]. [I enjoyed learning about] the neoadjuvant and adjuvant trials for NSCLC, as well as some of the newer immunotherapy agents that were discussed in various sessions.

Wolf: One of my favorite sessions was the multidisciplinary session on neoadjuvant vs adjuvant vs [perioperative] therapy. The session was titled early-stage lung cancer, but some of the cases and discussions centered around slightly more advanced diseases, such as stage II or III lung cancer. This meeting is a great setting in which to have everyone get involved in the discussion. Not only were there interesting data, but interesting points, subtleties, and real-life clinical examples were brought up.

Herrmann: The exciting movement in NSCLC right now is understanding how we're combining immunotherapies, whether we're looking at perioperative, neoadjuvant, or adjuvant approaches. There were very exciting plenary sessions looking at perioperative vs adjuvant approaches in earlier-stage cancers. There were a lot of exciting data presented, and lots more to come in that area.

I also attended another session about the [optimal] duration of immunotherapy. It is challenging to [determine] how long to treat our patients with immunotherapy [based on the current data], so hearing how different individuals and institutions are choosing how to treat their patients [with immunotherapy] is exciting.

Sands: One important study to highlight is the phase 2 NeoCOAST-2 study [NCT05061550]. The pCR rates after neoadjuvant therapy were quite good with some of these novel agents in the neoadjuvant space. That is encouraging for our efforts to cure patients who are diagnosed with earlier-stage diseases. Some of those will ultimately help more within the metastatic setting as well. However, [as the] efficacy of neoadjuvant therapy [increases], I'm hopeful that we'll be able to cure more people.

[This affirms] the importance of lung cancer screening. We have a number of people who qualify for lung screening but are not being screened. Our efforts at lung screening need to quadruple. We need most people who qualify for lung screening to undergo screening, as this is how we can diagnose cancers earlier. It's encouraging to see studies like NeoCOAST-2 that may lead to increased cure rates for patients with early-stage diagnoses.

Current and Emerging Biomarker-Driven Therapies

Roy: One of the big groups of studies that I felt were important looked at new drugs that target biomarkers in lung cancer. For example, targeting the HER2 biomarker in lung cancer is important, as is reimagining how we are treating EGFR-driven lung cancer. All EGFR mutations are not the same, and at this conference, we [saw] how certain types of EGFR mutations may require different drugs than what's been traditionally used. A highlight for me in this conference is reimagining how biomarker-driven lung cancers are treated.

Heymach: One area that's particularly interesting is the way now that we're starting to better personalize therapy for patients with EGFR mutations, particularly those with atypical EGFR mutations. The [phase 1b] FURTHER study [(FURMO-002; NCT05364073) evaluated] furmonertinib [AST2818] specifically in [patients with] EGFR PACC mutations. This is a group of patients we had identified who don't seem to benefit as much from standard third-generation TKIs. [Furmonertinib] had promising activity in EGFR PACC-mutant NSCLC. Now, we finally have some therapies tailored for these patients with EGFR PACC mutations, and we're excited to see new studies [assessing this agent] as well.

Garrasino: The phase 3 MARIPOSA study [NCT04487080] is another important clinical trial that showed that there is a benefit with amivantamab-vmjw [Rybrevant] plus lazertinib [Laclaza] vs osimertinib [Tagrisso]. Updated OS data were presented at the meeting and showed that there is a persistent benefit in terms of OS that is not statistically significant yet. [However, additional data showed that] if trends continue as they are, it is possible that this trial will become positive.

The big competitor is the phase 3 FLAURA-2 trial [NCT04035486], which also has a very high chance of [demonstrating] positive OS outcomes [with osimertinib plus chemotherapy]. Overall, the [treatment arsenal for] EGFR-mutant NSCLC will be very big, and we will have to decide whether to use osimertinib, another EGFR TKI [as monotherapy], or the combination of osimertinib and chemotherapy, or lazertinib plus amivantamab. In the future, we will [need to] work on refining biomarkers and [identifying] those patients who [would benefit from] a combination, and which [that is].

HER2 TKIs May Serve as Promising Second-Line Treatment Options

Leighl: We're all excited about fam-trastuzumab deruxtecan-nxki [Enhertu] and how it's improving outcomes in the second line setting, but wouldn't it be great if there were an oral version? There are 2 very exciting compounds: BAY 2927088, [which was evaluated in the phase 1/2 SOHO-01 trial (NCT05099172)] and zongertinib. [They have] great response rates of approximately 70%, great durations of response, and improved toxicity profiles. We're looking forward to a chance for a chance to use these new agents.

Le: I was glad to see data presented [from the phase Ib Beamion LUNG-1 study of] zongertinib [formerly BI 1810631], which is another HER2-targeted TKI. Both HER2 TKIs look very promising. [In the future], we are most likely going to see more opportunities and options for patients with HER2-expressing disease.

Antibody-Drug Conjugate (ADC) Developments Renew Fervor in Small Cell Lung Cancer (SCLC) and Beyond

Roy: We are seeing so much excitement in the treatment of SCLC, which is a treatment-refractory disease. For a long time, we had not seen any progress [in this space], so it is exciting to see a session [at the meeting] just dedicated to the use of [ADCs] in SCLC

Leighl: Very interesting data were presented on the TROP2 ADC, datopotamab deruxtecan [Dato-DXd], trying to measure the rate of receptor endocytosis and using artificial intelligence methods to do this. It speaks to the progress we're making in understanding who best responds to ADCs; it is central to this concept of drug uptake and lysis of the linker inside cells. We're looking forward to some of these biomarkers potentially moving forward and reaching prime time. Although we're a little ways away from that, we'll get there.

Novel Drug Delivery Platforms

Lau: What was very exciting about the 2024 IASLC World Conference on Lung Cancer was seeing a lot of the new drug delivery platforms come to fruition. T-cell engagers, which were first-in-class in solid tumors, are exciting. The other drug delivery platforms that we've seen make a difference when compared with pembrolizumab are bispecific antibodies. [The data show that a] bispecific creating conditional activation of that antibody can be superior and can improve the therapeutic index of a lot of these drug platforms. These drug delivery platforms allow us to combine targets in a creative fashion.

Patient-Centered Care and Quality of Life (QOL) Outcomes

Kingkalimanis: I'm always interested in QOL studies, and there's been some interesting work on this topic [presented at the meeting]. Investigators are starting to pull [QOL data] into consideration when [crafting] dosing [regimens]. For example, during the plenary session, there was talk of how a grade 3 level of diarrhea has a huge impact on activities of daily living [rivaling the concept of being] labeled a manageable or tolerable adverse effect [AE]. We're starting to talk about what it means to have a grade 3 AE of diarrhea and the impact that can have on someone's overall QOL. Greater recognition of that is [paramount].

Wolf: There was a session about clinicians [serving] as a second victim. The concept of moral injury and how both medical, surgical, and radiation oncologists take patient care very seriously [emphasizes] how very critical we are of ourselves. We often see the sometimes inevitable result of patients' diseases as a flaw in our treatment. [The session focused on] how to manage that and cope with that, both on an individual and a specialty level.

To check out more of OncLive’s coverage from the 2024 IASLC World Conference on Lung Cancer, click here.