The Targeted Pulse: Unpack The Latest FDA Approvals and Updates, Including A New Dosage For HER2 Cancers

New Dosage Approval For Trastuzumab in HER2-Overexpressing Cancers

The FDA has approved the 420-mg dose of the trastuzumab (Herceptin) biosimilar trastuzumab-strf (Hercessi; formerly HLX02), for the management of HER2-overexpressing cancers, including metastatic breast and gastric and gastroesophageal junction. The initial approval in April 2024 for the 150-mg dose was based on data from a phase 1 pharmacokinetic (PK) similarity trial and a global, multicenter, phase 3 trial (NCT03084237). In these trials, investigators reported a comparable safety profile to the reference product, trastuzumab, and the PK similarity met the FDA’s biosimilar guidance.

“The strength and success of our collaboration with Accord continues with the approval of the 420-mg strength of [trastuzumab-strf]. This represents an important step in our journey to meet the needs of patients with innovative, high quality, and affordable therapeutics,” said Jason Zhu, MD, executive director and chief executive officer of Henlius, in the press release.

First-Line Zolbetuximab Is Now Approved for CLDN 18.2+ Gastric/GEJ Cancer

First-line zolbetuximab (Vyloy) has received FDA approval for the treatment of locally advanced unresectable or metastatic HER2-negative gastric or gastroesophageal junction (GEJ) adenocarcinoma that is claudin (CLDN) 18.2-positive. This is the first CLDN 18.2-targeted therapy approved in this patient population.

This approval is based on data from the phase 3 SPOTLIGHT (NCT03504397) and GLOW (NCT03653507) trials. In the SPOTLIGHT trial, zolbetuximab plus 5-fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) was compared with placebo plus mFOLFOX6, and in the GLOW trial, zolbetuximab plus capecitabine and oxaliplatin (CAPOX) was compared with placebo plus CAPOX.

In January 2024, the FDA issued a complete response letter for zolbetuximab due to third-party manufacturing deficiencies; however, no concerns related to the clinical data of zolbetuximab were raised and the FDA did not request additional studies to support the biologic license application issued on May 9, 2024.

Pembrolizumab/Chemo Still Prevails in NSCLC With 5-Year Updates

Ticiana Leal, MD, provided 5-year updates of the KEYNOTE-407 trial (NCT02775435) data, evaluating the combination of chemotherapy plus pembrolizumab (Keytruda) for patients who were treatment-naïve, with non–small cell lung cancer (NSCLC) and squamous histology. In the trial, patients were randomly assigned 1:1 to receive pembrolizumab plus chemotherapy with the backbone of carboplatin plus paclitaxel followed by pembrolizumab maintenance for up to 31 cycles. This was compared with placebo plus chemotherapy and followed by placebo maintenance.

Leal also touches on long-term data from the phase 3 POSEIDON trial (NCT03164616) evaluating durvalumab with or without tremelimumab plus chemotherapy.

“When evaluating the breakdown by PD-L1 expression, what has been demonstrated across the KEYNOTE trials is that the higher the PD-L1 expression, the greater the magnitude of benefit from the combination,” said Leal, regarding the KEYNOTE-407 trial data. Leal is associate professor, Department of Hematology and Medical Oncology, director of Thoracic Medical Oncology Program at the Emory University School of Medicine Winship Cancer Institute in Atlanta, Georgia.

FDA Delays Decision on sNDA For Sotorasib/Panitumumab in Colorectal Cancer

The FDA has delayed its decision regarding the supplemental new drug application (sNDA) for sotorasib (Lumakras) plus panitumumab (Vectibix) in the management of chemorefractory metastatic colorectal cancer (CRC) with a KRAS G12C mutation. The targeted action date has been pushed to January 17, 2025. The delay is said to allow the FDA time to review supplemental information that was recently submitted, according to Amgen, the sponsor of the sNDA. The sNDA is based on data from the phase 3 CodeBreaK 300 study (NCT05198934), which was presented at the 2023 European Society for Medical Oncology Congress.

Later, the following year at the 2024 American Society of Clinical Oncology Annual Meeting, the data presented showed a lack of power to detect a statistically significant difference in overall survival (OS). Although, for those receiving the 960-mg dose of sotorasib with panitumumab, a trend toward OS improvement was observed.

LP-184 Moves Up a Peg With an FDA Fast Track Designation in Glioblastoma

LP-184 (STAR-001) has been granted fast track designation by the FDA for the treatment of glioblastoma (GBM). A phase 1b/2a study, evaluating the drug in patients with recurrent GBM, is set to begin either at the end of this year or early next year. The designation for this drug is intended for agents that treat serious conditions and fill unmet medical needs.

Investigators in a phase 1a study (NCT05933265) are currently evaluating LP-184 in advanced solid tumors, including GBM, with the goal of identifying the maximum tolerated dose.

“Receiving FDA fast track designation for Lantern Pharma’s LP-184 in GBM reinforces our belief that this drug-candidate can help in the critical need to find effective treatment options for patients with GBM and further supports the potential of LP-184 to address the challenges in aggressive [central nervous system] cancers, where patients have a critical need for novel and life extending therapies,” said Panna Sharma, president and chief executive officer of Lantern Pharma, in a press release.

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