Targeted Therapies, Frontline Combos Headline Key Lung Cancer Data to Emerge From ASCO 2026

As data emerged across the non–small cell lung cancer (NSCLC) space at the 2026 ASCO Annual Meeting, experts from the field outlined some of the most crucial findings that could impact future clinical approaches.

Find recaps of some of the meeting’s key lung cancer presentations and expert insights on their significance below.

Abstract LBA4: Ivonescimab plus chemotherapy versus tislelizumab plus chemotherapy in previously untreated advanced squamous non–small cell lung cancer: Overall survival results of the phase 3 HARMONi-6 trial

Findings from the interim analysis of the phase 3 HARMONi-6 trial (NCT05840016) showed that at a median follow-up of 21.36 months, the median overall survival (OS) was 27.89 months (95% CI, 27.89-not evaluable [NE]) in the ivonescimab arm (n = 266) vs 23.69 months (95% CI, 20.11-NE) in the tislelizumab-jsgr (Tevimbra) arm (n = 266), translating to a 34% reduction in the risk of death (HR, 0.66; 95% CI, 0.50-0.87; P = .0017); this crossed the prespecified efficacy boundary of one-sided P < .0049. The 12-month OS rates in the respective arms were 78.9% and 72.2%; the respective 24-month OS rates were 64.7% and 48.6%.

The OS benefit was consistent across key subgroups, including those defined by sex, age, ECOG performance status, disease stage, PD-L1 expression, and brain metastases. By PD-L1 status, the OS HR was 0.64 (95% CI, 0.43-0.96) in those with a PD-L1 tumor proportion score (TPS) less than 1% and 0.68 (95% CI, 0.46-0.99) in those with a PD-L1 TPS of 1% or higher; within the PD-L1–positive group, the HR was 0.76 (95% CI, 0.42-1.05) in patients with a PD-L1 TPS ranging from 1% to 49% and 0.64 (95% CI, 0.32-1.31) in those with a TPS of 50% or higher.

Tony S.K. Mok, MD, BMSc, FRCP(C), FRCP(Edin), FHKCP, FHKAM(Medicine), FASCO

Chinese University of Hong Kong

“In the plenary, we saw the OS results from the Chinese HARMONi-6 trial, which evaluated the use of chemotherapy plus ivonescimab vs chemotherapy plus tislelizumab. The authors were able to demonstrate an improvement in PFS previously and now an improvement in OS. With that OS benefit, then the question is, what is the role of bispecific [antibodies] in our future management [paradigm]? This is China-only data, but Summit Therapeutics has already taken the rights to this medication, and the ongoing phase 3 HARMONi-3 study [NCT05899608] may potentially deliver the answer to this [question].”

Jonathan Goldman, MD

University of California, Los Angeles

“This is the first trial to clearly demonstrate an overall survival benefit with the use of ivonescimab, and this may translate to many other trials. In particular, we want to see those results duplicated in the Western population. We do know there are differences between the Asian and Western populations in the benefits of some of these therapies, so seeing as strong a benefit in, for example, the upcoming HARMONi-3 trial would be very exciting and may lead to our consideration of some of the other ivonescimab trials, including the [phase 3] HARMONi trial [NCT06396065], which I participated in, and some other bispecific drugs.”

Abstract LBA3: Event-free survival with adjuvant selpercatinib in stage IB-IIIA RET fusion–positive NSCLC: Primary results of the phase 3 LIBRETTO-432 trial

Primary data from the phase 3 LIBRETTO-432 study (NCT04819100) demonstrated that selpercatinib (Retevmo) led to an 83% reduction in the risk of disease recurrence or death vs placebo when used in the adjuvant treatment of patients with stage II to IIIA, RET fusion–positive NSCLC. The event-free survival (EFS) improvement with selpercatinib was determined to be statistically significant, and the primary end point of the study was met (HR, 0.172; 95% CI, 0.058-0.509; P = .0003). The 24-month EFS rate with selpercatinib was 91.5% (95% CI, 75.4%-97.2%) vs 61.1% (95% CI, 44.2%-74.3%) with placebo.

Overall survival data were immature with median follow-ups of 25 (IQR, 13.9-33.2) and 27 (IQR, 15.8-34.1) months in the selpercatinib and placebo arms, respectively. At the time of the analysis, zero deaths were reported in the selpercatinib arm vs 3 in the placebo arm. Sixteen patients crossed over to the selpercatinib arm following disease recurrence, 12 of whom remained on selpercatinib at data cutoff. All 3 deaths occurred at least 1 year after the start of crossover.

Joel Neal, MD, PhD

Stanford Health Care

“I treat patients on the West Coast, most without a smoking history. We see a lot of mutations beyond EGFR that have unmet need. We saw new data in the RET gene–rearranged setting. In the advanced metastatic setting, we have a number of RET inhibitors that are FDA approved. We also saw updated first-line data with crizotinib [Xalkori] in RET-rearranged NSCLC, as well as a novel RET inhibitor that looks like it may have high activity too. More exciting to me is probably a new indication for selpercatinib in the adjuvant setting after curative intent surgery for RET-[rearranged NSCLC], based on the plenary presentation Jonathan Goldman, MD, gave. These data will probably change practice.”

Estelamari Rodriguez, MD, MPH

University of Miami

“LIBRETTO-432 speaks to how we use targeted therapies in earlier-stage disease. Now, we’re going to have a third targeted therapy that we can use in early-stage disease with selpercatinib for RET fusion–positive stage IB to IIIA NSCLC. The results showed an [EFS HR] of 0.172, so an 83% reduction in progression for patients [who] had surgery and had this biomarker identified and had the proper therapy compared with placebo. The bottom line is that biomarker testing and the investment in finding all the other biomarkers that we don't know now is where we need to go, because that's what's showing the [best] data. [Another area we need to focus on is understanding how] we screen people who are never smokers. We know the RET fusion–positive lung cancer population can benefit, but if we don't identify them early, they'll be treated for metastatic disease, which is incurable. Second, if we don't test for biomarkers at the time of surgery, then we miss this opportunity. Now it's really a standard of care that you should [test], because you not only have RET, you have ALK and EGFR as therapies that need to be tested for in early-stage disease. Unfortunately, only a quarter of patients with lung cancer present with early-stage disease. I do think the biomarker studies still win in lung cancer, but [we still need dedicated research] to address the needs of everybody else who doesn't have an actionable mutation.”

Bruna Pellini, MD

Baptist Health Miami Cancer Institute

“Some of the key messages are that yes, we can design trials for patients with rare cancers. Christine Lovly, MD, PhD, FASCO, [of City of Hope], did an amazing discussion questioning and challenging the idea that we have to do a trial for each single fusion that can happen in lung cancer. Can we start to extrapolate a little and understand that every trial we have done so far has shown positive results with low [HRs], showing how much better targeted treatment is in this setting? This is something we have to start questioning because it takes years and a lot of resources to run a phase 3 global trial. Are we using the clinical trial resources in the best way? Is there a more pragmatic way to potentially get drugs approved if we know they work well in the metastatic setting? I know this is a bit of a philosophical question. There are a lot of financial and safety implications as well, but we all understand how long it takes for a drug to be developed and for new approvals to happen. I wonder if there’s an opportunity for us to give access to our patients earlier and not wait 10 years to give something that we have strong signs to believe is going to be the best treatment opportunity.”

Abstract 8506: Sacituzumab tirumotecan (sac-TMT) plus pembrolizumab (P) versus pembrolizumab (P) as first-line treatment for PDL1–positive advanced non-small cell lung cancer (NSCLC): Results from the randomized phase 3 OptiTROP-Lung05 study

Interim data from the phase 3 OptiTROP-Lung05 study (NCT06448312) demonstrated that the addition of the TROP2-directed antibody-drug conjugate sacituzumab tirumotecan (sac-TMT; SKB264/MK-2870) to pembrolizumab (Keytruda) significantly improved progression-free survival (PFS) vs pembrolizumab alone when used in the first-line treatment of patients with PD-L1–positive advanced non-small cell lung cancer.

At a median follow-up of 10.5 months, the median PFS by blinded independent central review was not reached (NR; 95% CI, 13.6-not evaluable) with sac-TMT plus pembrolizumab (n = 208) vs 5.7 months (95% CI, 4.3-7.0) with pembrolizumab alone (n = 205), translating to a 65% reduction in the risk of disease progression or death (HR, 0.35; 95% CI, 0.26-0.47; P < .0001). The 12-month PFS rates were 62.4% and 29.0%, respectively. The PFS benefit was consistent across PD-L1 and histology subgroups. The combination also improved response. The objective response rate was 70.2% with sac-TMT plus pembrolizumab vs 42.0% with pembrolizumab alone in the intention-to-treat population.

Jonathan Goldman, MD

University of California, Los Angeles

“There are others in the same class, and other exciting bispecific antibodies and bispecific antibody-drug conjugates that are likely an important part of our future options. There was an exciting presentation using sac-TMT with pembrolizumab vs pembrolizumab alone, with [an HR] of 0.35, which was quite exciting. This was for all patients with PD-L1 [tumor proportion score] of 1% or greater, so not exactly the comparator that we might have chosen, particularly for the 1% to 49% expressors, but even in the 50% and higher expressors, there was a benefit. It would also be interesting to see in both of those groups how the combination would compare with chemotherapy plus pembrolizumab, but it is clear that sac-TMT is a very meaningful drug that will have a place in our treatment armamentarium.”

Abstract 8502: Lorlatinib vs crizotinib as first-line treatment for advanced ALK+ non-small cell lung cancer: 7-year update from the phase 3 CROWN study

At a median follow-up of 83.0 months (95% CI, 81.2-86.3) for lorlatinib (Lorbrena; n = 149) and 77.2 months (95% CI, 36.8-not evaluable) for crizotinib (Xalkori; n = 147), the 7-year update of the phase 3 CROWN study (NCT03036488) showed that the median progression-free survival (PFS) was still not reached (NR; 95% CI, 68.5 months-NR) vs 9.1 months (95% CI, 7.4-10.9), respectively (HR, 0.19; 95% CI, 0.13-0.26), in patients with advanced ALK-positive non-small cell lung cancer. The 7-year PFS rates in the respective arms were 55% vs 3%. In total, 7 new PFS events were reported between 5 and 7 years in the lorlatinib arm; 4 were progression events, and 3 were deaths (all of which were deemed not related to treatment).

No new intracranial (IC) progression events occurred after the first 30 months on lorlatinib. The median times to IC progression were NR (95% CI, NR-NR) and 16.4 months (95% CI, 12.7-21.9), respectively (HR, 0.06; 95% CI, 0.03-0.12). The 7-year IC PFS rates were 92% vs 16%, respectively.

Among patients with baseline brain metastases, the time to IC progression was NR (95% CI, NR-NR) in the lorlatinib arm (n = 35) vs 7.2 months (95% CI, 3.7-11.0) in the control arm (n = 38; HR, 0.03; 95% CI, 0.01-1.13). Among patients without baseline brain metastases, the time to IC progression was NR (95% CI, NR-NR) in the lorlatinib arm (n = 114) vs 23.9 months (95% CI, 16.4-30.8) in the control arm (n = 109; HR, 0.04; 95% CI, 0.02-0.12).

Estelamari Rodriguez, MD, MPH

University of Miami

“The CROWN data that are presented again and again are extremely exciting. To see 7-year data from a targeted therapy in an incurable lung cancer, where not even half the patients have progressed at 7 years, is remarkable. We saw the 5-year CROWN data, and that was a big celebration. I don’t think people anticipated that they would have as many patients at 7 years as they did at 5 years. That speaks to how lung cancer is becoming a chronic disease for young people, and that if we develop the best therapies that overcome resistance from the beginning and treat central nervous system disease, we will see these long-term survivals in lung cancer. What that tells me is that the promise of targeted therapy for long-term survivorship is there. That being said, [ALK-positive disease represents] only 3% of lung cancer.”

Karen Reckamp, MD

Cedars-Sinai

“ASCO 2026 was groundbreaking, especially for thoracic oncology… The updated PFS data from the CROWN study, now showing a median that’s reached more than 7 years…exemplifies where we are in thoracic oncology. Two decades ago, this was a very difficult-to-treat disease without a lot of options outside of chemotherapy. Now we're looking at PFS in a subset of patients that's over 7 years, which is remarkable. There's a lot to be excited for in the future from this meeting.”

Abstract 8004: Redefining lung cancer screening eligibility: Smoking duration vs pack-years in a national VA cohort of nearly 1 million patients

A retrospective cohort study of 980,399 veterans aged 50 to 80 years in the Veterans Health Administration found that smoking duration performed at least as well as tobacco pack‑years in predicting lung cancer risk and substantially expanded screening eligibility with fewer missed cancers. Tobacco smoking duration criteria were also associated with improved equity. These findings support revisiting national lung cancer screening guidelines to prioritize smoking duration over pack-years.

Coral Olazagasti, MD

University of Miami

“I was excited to see some of the smaller, oral presentations. One exciting one in screening was taking into consideration duration of smoking instead of pack-years. That’s exciting to see because at the end of the day, we want to capture more at-risk participants in the earlier stages. Early detection, which is something that I am very passionate about, is very important to talk about. All in all, I’m excited about the data that are coming.”

Abstract 8510: First-line (1L) divarasib plus pembrolizumab (pembro) in advanced or metastatic KRAS G12C+ non–small cell lung cancer (NSCLC): Results from the KRAScendo-170 study

In the phase 1b/2 KRAScendo 170 trial (NCT05789082), the combination of divarasib (GDC-6036) plus pembrolizumab demonstrated encouraging activity as frontline therapy in patients with unresectable, advanced, or metastatic KRAS G12C–mutant NSCLC. In patients with PD-L1–positive disease, the confirmed objective response rate (ORR) was 72.9% (95% CI, 59.7%-83.6%), and the median duration of response was not evaluable (NE; 95% CI, 14.5-NE). The median progression-free survival (PFS) was 19.3 months (95% CI, 12.4-NE); the 6-month PFS rate was 83.5% (95% CI, 73.6%-93.3%). In the PD-L1–negative cohort, the unconfirmed ORR was 69.6% (95% CI, 47.1%-86.8%). In both cohorts, responses were observed regardless of KEAP1 and STK11 status.

Benjamin Herzberg, MD

Columbia University Herbert Irving Comprehensive Cancer Center

“One of the abstracts that caught my eye in lung cancer was the KRAScendo 170 trial, which was this proof of principle for a [KRAS] G12C inhibitor plus pembrolizumab. The response rates are extremely high, 70% to 80%, in the first line without chemotherapy, showing that if you have a potent enough G12C inhibitor, you may be able to reserve chemotherapy for later lines and combine it with immunotherapy in what we know is an immunotherapy-responsive population. The randomized [phase 3] Krascendo 2 trial [NCT06793215] is ongoing, and we’ll see what that shows.”

Abstract 8002: Neoadjuvant lorlatinib in stage III NSCLC harboring ALK fusion: A phase 2 multicenter study (LORIN)

In this phase 2 study (NCT05740943), neoadjuvant lorlatinib elicited high rates of pathologic complete response (pCR) and surgical conversion in patients with unresectable stage III ALK-positive NSCLC. In the overall population (n = 32), the pCR rate was 46.9% (95% CI, 29.1%-65.2%), and the major pathologic response rate was 81.3%. Among patients with resectable disease, these respective rates were 50% and 86%. Among patients with unresectable disease, these respective rates were 44% and 78%.

Bjørn Grønberg, MD, PhD

Norwegian University of Science and Technology

“One of the biggest changes in our management of lung cancer in recent years is our introduction of neoadjuvant chemoimmunotherapy. For some reason, we haven’t seen successes in targeted neoadjuvant treatment, so the data on neoadjuvant lorlatinib with high rates of pCR are promising. Maybe this can be the first time that neoadjuvant targeted therapy is established.”