Luis Paz-Ares, MD, PhD, chairman, Medical Oncology Department, Hospital Doce de Octubre; head, Lung Cancer Unit, CNIO (National Oncology Research Center); associate professor, Universidad Complutense, discusses efficacy and safety findings from the phase 2 CARMEN-LC05 trial (NCT04524689) of tusamitamab ravtansine (SAR408701) in patients with nonsquamous non–small cell lung cancer (NSCLC) with CEACAM5 expression.

CARMEN-LC05 investigated the efficacy and safety of tusamitamab ravtansine in doublet, triplet, and quadruplet combinations with pembrolizumab (Keytruda) with or without platinum-based chemotherapy and pemetrexed (Alimta) in patients with nonsquamous NSCLC with moderate to high CEACAM5 expression and any level of PD-L1 expression. In all treatment arms, patients received tusamitamab ravtansine intravenously every 3 weeks at either 150 mg/m

Across all dose levels, the overall response rate (ORR) was 52% (95% CI, 31.3%-72.2%), and the median duration of treatment was 24.3 weeks. Additionally, 36% of patients achieved stable disease, 12% of patients had progressive disease, and the disease control rate was 88% (95% CI, 68.8%-97.5%).

The ORRs with the doublet, triplet, and quadruplet with tusamitamab ravtansine at 150 mg/m

 were 100%, 50%, and 50%, respectively. Responses were seen in patients regardless of PD-L1 or CEACAM5 expression, Paz-Ares says.

The doublet, triplet, and quadruplet regimens were tolerable, Paz-Ares notes. One dose-limiting toxicity, increased aspartate aminotransferase, was seen in a patient who received tusamitamab ravtansine at 170 mg/m

 as part of the quadruplet regimen. Treatment-emergent adverse effects (TEAEs) of grade 3 or higher occurred in 68.0% of all patients, however, most were unrelated to the study regimens, Paz-Ares explains. In addition, 24.0% of all patients had corneal TEAEs, which were manageable with dose modification, Paz-Ares emphasizes. One patient in the doublet arm who received tusamitamab ravtansine at 170 mg/m

 experienced a grade 3 corneal TEAE. Furthermore, 16.0% and 28.0% of all patients had pneumonitis and peripheral neuropathy, respectively, and most events were grade 1/2, Paz-Ares concludes.

Editor's Note: This summary reflects the accurate value for the median duration of the study treatment, which was 24.3 weeks, rather than 24 months, as noted in the video at 0:28.

Paz-Ares L, Nagy T, Ravoire M, et al. Safety and efficacy of tusamitamab ravtansine in comination with pembrolizumab ± chemotherapy in patients with CEACAM5-positive nonsquamous NSCLC (CARMEN-LC05 phase 2 study). Presented at: 2023 European Lung Cancer Congress; March 29-April 1, 2023; Copenhagen, Denmark. Abstract 13MO.

Videos

Luis Paz-Ares, MD, PhD, discusses efficacy and safety findings from the phase 2 CARMEN-LC05 trial of tusamitamab ravtansine in patients with nonsquamous non–small cell lung cancer with CEACAM5 expression.

Dr Paz-Ares on Tusamitamab Ravtansine in CEACAM5-Positive NSCLC

Luis G. Paz-Ares, MD, PhD, chair, the Medical Oncology Department, the Hospital Universitario 12 de Octubre, associate professor, the Universidad Complutense de Madrid, head, the Lung Cancer Unit, the National Oncology Research Center, discuses the importance of nivolumab (Opdivo) plus ipilimumab (Yervoy) in the treatment of patients with metastatic non–small cell lung cancer (NSCLC).

The phase 3 CheckMate-9LA trial (NCT03215706) evaluated nivolumab and ipilimumab with chemotherapy vs chemotherapy alone as a first-line treatment for patients with metastatic NSCLC.

The combination regimen increased overall survival across most subsets of patients, irrespective of PD-L1 status and histology, Paz-Ares says. Data also showed benefits were observed in all subgroups in progression-free survival, overall response rate, and the duration of response with 2 courses of nivolumab/ ipilimumab plus chemotherapy compared with chemotherapy alone, Paz-Ares explains.

As a part of the study, a mutational analysis of patients was completed, including those with nonsquamous histology, Paz-Ares adds. Relevant mutations in NSCLC were not predictive of outcomes for treatment with nivolumab/ipilimumab plus chemotherapy vs chemotherapy alone, Paz-Ares concludes.

Luis G. Paz-Ares, MD, PhD, discuses the importance of nivolumab plus ipilimumab in the treatment of patients with metastatic non–small cell lung cancer.

Dr. Paz-Ares on Nivolumab/Ipilimumab Plus Chemotherapy in NSCLC

Luis Paz-Ares, MD, PhD, Professor of Medicine at Hospital Universitario 12 de Octubre in Madrid, Spain, discusses a subgroup analysis of patients with EGFR-expressing tumors from the SQUIRE trial, a phase III study of gemcitabine—cisplatin plus necitumumab versus gemcitabine–cisplatin alone as first-line treatment for patients with stage IV squamous non-small cell lung cancer (NSCLC).

The SQUIRE trial was positive for the combination in the overall population. The goal of the analysis was to determine if there was a correlation between EGFR-expressing tumors and response to gemcitabine—cisplatin plus necitumumab, says Paz-Ares.

The results showed that patients that were EGFR-positive did benefit from the triple combination and the benefit was at least as high as the overall population, says Paz-Ares. The 5% if patients who did not have any EGFR-expression, did not experience any benefit from necitumumab, says Paz-Ares.

The data from non-expressing tumors is based on a very small patient population and Paz-Ares says he would not recommend excluding non-EGFR patients from receiving necitumumab at this time. It is, however an area that should be explored further, he says.

View more from the 2016 European Lung Cancer Conference

Luis Paz-Ares, MD, PhD, Professor of Medicine at Hospital Universitario 12 de Octubre in Madrid, Spain, discusses a subgroup analysis of patients with EGFR-expressing tumors from the SQUIRE trial, a phase III study of gemcitabineâ€“cisplatin plus necitumumab versus gemcitabineâ€“cisplatin alone as first-line treatment for patients with stage IV squamous non-small cell lung cancer (NSCLC).


Dr. Paz-Ares on Connection of EGFR-Expression and Necitumumab Response in NSCLC

Luis Paz-Ares, MD, PhD the chair of oncology at Seville University Hospital in Spain discusses the use of pemetrexed in advanced nonsquamous non—small cell lung cancer.

Dr. Paz-Ares From Seville University Hospital Discusses the Use of Pemetrexed for NSCLC

Dr. Paz-Ares Discusses the Use of Pemetrexed for NSCLC

Luis Paz-Ares, MD, PhD, chair of Oncology at Seville University Hospital in Spain, discusses the pemetrexed advanced nonsquamous non—small cell lung cancer clinical trial.

Dr Paz-Ares from Seville University Hospital Discusses Pemetrexed Clinical Trial

Luis Paz-Ares, MD, PhD

Articles

Dr Paz-Ares on Tusamitamab Ravtansine in CEACAM5-Positive NSCLC

Dr. Paz-Ares on Nivolumab/Ipilimumab Plus Chemotherapy in NSCLC

Dr. Paz-Ares on Connection of EGFR-Expression and Necitumumab Response in NSCLC

Dr. Paz-Ares Discusses the Use of Pemetrexed for NSCLC

Dr. Paz-Ares Discusses Pemetrexed Clinical Trial