The Targeted Pulse: SC Pembrolizumab Combo Matches SOC in NSCLC and CAR T-cells Transform the Solid Tumor Space

“Chemotherapy/Pembrolizumab SC is Noninferior to SOC” in NSCLC

In the phase 3 3475A-D77 study (NCT05722015), subcutaneous (SC) pembrolizumab (Keytruda) compared with intravenous (IV) pembrolizumab plus chemotherapy demonstrated non-inferior efficacy in metastatic non–small cell lung cancer (NSCLC). In this video, Enriqueta Felip, MD, PhD, explains the trial data regarding the trial design.

“In patients with lung cancer, the combination of chemotherapy plus pembrolizumab IV is standard of care for those patients without genomic alterations, and this is a randomized trial including patients with untreated stage IV non–small cell lung cancer and no alterations,” Felip, section chief at the Vall d'Hebron University Hospital, head of the Vall d' Hebron Institute of Oncology’s thoracic tumors group, Universitat Autònoma de Barcelona, Spain, explains. Access the full video here.

Discussion on Optimizing Outcomes for High-Risk CML Into Blast Phase

Although the management of chronic myeloid leukemia (CML) has advanced in recent years, challenges persist in optimizing outcomes, particularly for those who have high-risk CML and those progressing to blast phase. In this article, Akriti Jain, MD, provides insight into the gaps in standardized regimens in blast-phase and discusses the impact of non-ABL1 mutations such as ASXL1 and RUNX1 in CML.

“A lot of patients, especially younger patients (where we see blast-phase CML), have been through multiple tyrosine kinase inhibitors [TKIs] used for CML treatment, and they have burned through some of these TKIs because they were not taking them consistently. This can lead to mutations in the ABL1 tyrosine kinase domain, causing resistance. Resistant disease then leads to progression,” Jain, Department of Hematology and Medical Oncology, Cleveland Clinic explained. Access the full discussion here.

Insights on the CAR T-Cell Field Advancing into the Solid Tumor Realm

Robert L. Ferris, MD, PhD, shares exciting information on upcoming advancements in the field of oncology, highlighting key presentations from the recent American Society of Clinical Oncology Gastrointestinal Cancers Symposium and the European Hematology Association/ European Bone Marrow Transplant 7th Chimeric Antigen Receptor (CAR) T-Cell Meeting. Ferris discussed that CAR T-cell therapy is making headway in the treatment of solid tumors. In addition, Ferris noted that hepatocellular carcinoma and BRAF-mutated colorectal cancer may benefit from multikinase-targeted inhibitors.

“Given the 5 or more hematologic cancers with approved cell therapies, we can expect future novel cellular approaches and clinical trials with extended clinical end points rather than simply first-in-human or toxicity questions being resolved,” wrote Ferris, Lineberger Distinguished Professor, executive director, UNC Lineberger Comprehensive Cancer Center and chief of Oncology Services, UNC Health System, Chapel Hill, North Carolina. Check out the full overview here.

Success With Subcutaneous Administration of Pembrolizumab in NSCLC

In addition to the above video by Felip on the randomized, open-label 3475A-D77 study, this article delves deeper into the noninferior pharmacokinetic success of SC pembrolizumab with chemotherapy vs IV pembrolizumab with chemotherapy in metastatic NSCLC. In the trial, as first line therapy, 377 patients with metastatic NSCLC were randomly assigned to receive SC pembrolizumab with berahyaluronidase alfa (MK-3475A; SC pembrolizumab) plus chemotherapy, or IV pembrolizumab and chemotherapy. The median injection time with the SC pembrolizumab combination was 2 minutes.

“[Pembrolizumab] has helped transform the treatment of certain cancers, and we continue to pursue innovations that build on this breakthrough medicine to give patients and those who treat them better experiences,” said Marjorie Green, MD, senior vice president and head of oncology, global clinical development, Merck Research Laboratories. “If approved, we are excited about the potential of subcutaneous pembrolizumab to become a new meaningful treatment option that may increase access and save time needed for administration compared with IV [pembrolizumab].” For more trial data, access the full article here.

Insights on Full Approval of Pembrolizumab/Trastuzumab for HER2+ Gastric Cancer

In this video, Yelena Y. Janjigian, MD, offers further insight into data from the phase 3 KEYNOTE-811 trial (NCT03615326), which supported the recent approval of pembrolizumab plus trastuzumab (Herceptin) and chemotherapy for HER2-positive locally advanced unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma. Janjigian also provides insight into how this approval may affect the community setting by preparing clinicians to incorporate this new treatment combination for their patients.

“Pembrolizumab in combination with trastuzumab and chemotherapy has been a practice-changing treatment for HER2-positive disease. In fact, even as far back as 2019, when we initially were accruing to the phase 3 study in the US, we had trouble randomizing patients to the non-pembrolizumab-containing arm because many…were aware of our initial phase 2 data that we published in Lancet Oncology, and they did not want to be randomized to the non-pembrolizumab-containing arm,” explains Janjigian, chief attending physician of the Gastrointestinal Medical Oncology Service, Memorial Sloan Kettering Cancer Center in New York, New York. Access the full video here.

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

In case you missed it, here is last week’s Targeted Pulse.