Isabel Preeshagul, DO, MBS, and colleagues share updates from across the lung cancer space as discussed in a recent State of the Science Summit.

Lung Cancer State of the Science Summit Recap

 on Lung Cancer chaired by Isabel Preeshagul, DO, MBS, she and colleagues highlight key takeaways from their presentations, which covered updates from across the lung cancer treatment paradigm. Preeshagul is a thoracic medical oncologist and assistant attending physician at Memorial Sloan Kettering Cancer Center.

Preeshagul discusses the clinical implications of 

data from the phase 3 ADRIATIC trial (NCT03703297)

, which showed that patients with limited-stage small cell lung cancer (LS-SCLC) whose disease has not progressed following platinum-based concurrent chemoradiotherapy experienced a median overall survival of 55.9 months (95% CI, 37.3-not evaluable) when treated with durvalumab (Imfinzi; n = 264) compared with 33.4 months (95% CI, 25.5-39.9) when given placebo (n = 266; HR, 0.73; 95% CI, 0.57-0.93; 

 = .0104). Based on these data, In August 2024, 

 to the supplemental biologics license application seeking the approval of durvalumab for the treatment of patients with LS-SCLC whose disease has not progressed following platinum-based concurrent chemoradiotherapy.

Next, Alissa J. Cooper, MD, a thoracic medical oncologist and assistant attending physician at Memorial Sloan Kettering Cancer Center, highlights the evolving understanding of the role of antibody-drug conjugates in the treatment of patients with non–small cell lung cancer (NSCLC). Cooper expands on the challenges posed in the clinical study of these agents and how biomarkers could help refine the understanding of which patients may benefit most from these agents.

Kathryn C. Arbour, MD, a thoracic medical oncologist and assistant attending physician at Memorial Sloan Kettering Cancer Center, then delves into the current treatment paradigm for patients with NSCLC harboring 

 G12C mutations. She details the prevalence of 

 mutations in this patient population and how ongoing research could build upon the targeted therapies available for those with 

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Lung Cancer State of the Science Summit Recap | Chaired by: Isabel Preeshagul, DO, MBS

Dr Arbour on the Safety and Efficacy of RMC-6236 in KRAS-Mutant NSCLC

Kathryn C. Arbour, MD, assistant attending physician, Memorial Sloan Kettering Cancer Center, discusses preliminary safety and efficacy data with the RAS inhibitor RMC-6236 in patients with 

-mutated non–small cell lung cancer (NSCLC).

At the 2023 ESMO Congress, Arbour presented findings from the phase 1 RMC-6236-001 trial (NCT05379985) which evaluated treatment with RMC-6236 at 80 mg and above in patients with NSCLC and pancreatic ductal adenocarcinoma (PDAC) harboring 

 G12C mutations. Evaluating the safety profile of this agent in patients with NSCLC is important because the tolerability of pan-RAS inhibitors is unknown, Arbour says.

RMC-6236 was well tolerated at clinically active doses in patients with NSCLC, Arbour explains. The most common treatment-related adverse effects (TRAEs) reported in all safety-evaluable patients with NSCLC and PDAC treated with at least 80 mg of RMC-6236 per day (n = 111) were rash, nausea, diarrhea, vomiting, stomatitis, and fatigue, most of which were grade 1/2 and generally well managed with supportive medications such as topical steroids and oral antibiotics, Arbour notes. Importantly, only 14% of patients with NSCLC or PDAC required dose reduction because of TRAEs of any grade, and only 1 patient (1%) discontinued treatment due to TRAEs. The safety findings with RMC-6236 supplement the efficacy findings by showing that patients can maintain treatment with consistent doses of this agent, Arbour emphasizes.

Regarding the clinical activity of RMC-6236, of 40 patients with NSCLC who initiated treatment with RMC-6236 at 80 mg per day or more at least 8 weeks prior to data cutoff, 1 patient (3%) achieved a complete response, and 14 patients (35%) experienced a partial response, translating to an overall response rate of 38%. Furthermore, 48% of patients had a best overall response of stable disease, and the disease control rate was 85%. Twenty-eight patients remained on treatment at the data extract date.

The responses seen with RMC-6326 in patients with NSCLC are durable, and further follow-up data may show deepening of these responses over time, Arbour emphasizes. Moreover, the median time to response was 1.4 months (range, 1.2-2.7), indicating that this agent provided symptom relief for patients shortly after treatment initiation, Arbour concludes.

Dr Arbour reports consulting roles with Amgen, Novartis, G1 Therapeutics, AstraZeneca, and Sanofi-Genzyme; and institutional research funding from Genentech (local PI), Mirati Therapeutics (local PI), and Revolution Medicines (local PI).

Clinicians referring a patient to MSK can do so by visiting msk.org/refer, emailing referapatient@mskcc.org, or by calling 833-315-2722.

Kathryn C. Arbour, MD, discusses preliminary safety and efficacy data with the RAS inhibitor RMC-6236 in patients with KRAS-mutated non–small cell lung cancer.

Kathryn C. Arbour, MD

Articles

Lung Cancer State of the Science Summit Recap | Chaired by: Isabel Preeshagul, DO, MBS

Dr Arbour on the Safety and Efficacy of RMC-6236 in KRAS-Mutant NSCLC