The Targeted Pulse: Groundbreaking Research in Small Cell Lung Cancer, Myeloma, and More

Brentuximab Vedotin Delivers Survival Improvement in R/R DLBCL

Brentuximab vedotin (Adcetris) and lenalidomide plus rituximab (Rituxan) showed a significant overall survival (OS) improvement when compared with lenalidomide and rituximab plus placebo for patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). These results, as well as improvements in progression-free survival and overall response rate, were observed in the phase 3 ECHELON-3 trial (NCT04404283).

“This is the third phase 3 study in a type of lymphoma to demonstrate an OS benefit for [the brentuximab vedotin] combination. Based on the strong results from ECHELON-3, we’re excited that [brentuximab vedotin] could address an area of high unmet need in patients with relapsed or refractory DLBCL irrespective of CD30 expression,” Roger Dansey, MD said. Dansey is chief development officer of oncology at Pfizer.

A Promising New Strategy Targets GPRC5D in Multiple Myeloma Using BMS-986393

Novel immunotherapeutic strategies now include targeting the GPRC5D receptor expressed in multiple myeloma cells to enhance the current armamentarium of the disease. The development shows significant potential.

“This product, BMS-986393 [CC-95266], is a second generation autologous chimeric antigen receptor [CAR] T-cell that’s also targeting GPRC5D. It is similar to the Memorial Sloan Kettering product with some differences in manufacturing,” Susan Bal, MD, explained. “In the phase 1 program [NCT04674813] so far, which is still ongoing…The safety profile looks manageable, with toxicities being limited in the sense that it affects only about a quarter or less of the patients…[and] we did see a significantly high efficacy,” Bal said. Bal is assistant professor, hematology, medical oncology, University of Alabama at Birmingham (UAB), UAB Health, O’Neal Comprehensive Cancer Center.

Lurbinectedin Triumphs Over Topotecan in Small Cell Lung Cancer

When compared with topotecan, patients with small cell lung cancer (SCLC) experienced a more positive benefit/risk ratio of treatment with lurbinectedin (Zepzelca), according to a post hoc analysis highlighting data from the phase 3 ATLANTIS study (NCT02566993). Benefit was found in patients who were chemotherapy-free for 30 days or longer and with no central nervous system metastases.

“Lurbinectedin is more active, as measured by all usual outcomes metrics, and is clearly less toxic and better tolerated than topotecan. An ongoing confirmatory phase 3 trial [LAGOON; NCT05153239] is evaluating lurbinectedin as single agent or in combination with irinotecan vs topotecan or irinotecan in the population of adult SCLC patients who have failed one prior platinum-containing line with [a chemotherapy-free interval] of 30 days or more and controlled asymptomatic CNS metastases,” study authors wrote in An International Journal for Lung Cancer and other Thoracic Malignancies.

Steps Forward in Small Cell Lung Cancer Management

Ariel Lopez-Chavez, MD discusses the development of treatment strategies for small cell lung cancer management, highlighting the phase 2 basket trial (NCT02454972) and updated guidelines. Lopez-Chavez is a medical oncologist, director of precision medicine and developmental therapeutics at Allegheny Health Network Cancer Institute.

“[There is another] combination of agents in the frontline setting to [see if] the use of PD-1/PD-L1 inhibitors are more effective. The trial is a phase 3 study [NCT05091567] where lurbinectedin is added to atezolizumab in the maintenance setting for extensive-stage small cell lung cancer…This will be an interesting study to see because lurbinectedin is now approved in the second-line setting. It will be interesting to see what the efficacy is bringing it to the maintenance setting,” Lopez-Chavez explained.

Unique Vulnerabilities in Pancreatic Cancer Subtypes Are Advancing the Field

The identification of subtypes in pancreatic cancer such as pancreatic ductal adenocarcinoma (PDAC), pancreatic adenosquamous carcinoma (PASC), and pancreatic squamous cell carcinoma are allowing for new approaches. Pat Gulhati’s, MD, PhD, research shows variation in mutation rates in specific genes and amplifications in others. Gulhati is an assistant professor at the Rutgers Robert Wood Johnson Medical School in New Brunswick, New Jersey.

“The first finding,” Gulhati explained, “is that we identified several genes which had higher mutation rates in PASC compared with PDAC. Some of these genes included CDKN1B, SF3B1, PTEN, [and] BCL9. There were amplifications in AKT2, which were higher, and also ROS1 fusions, which were higher in PASC cancers,” he said.

Thank you for joining us for this week’s Targeted Pulse. Look out for more recaps to come.