The Targeted Pulse: Amivantamab/Lazertinib Scores Points in NSCLC, Nivolumab Boosts Treatment for Uterine and Ovarian Cancers, and More

Frontline Amivantamab/Lazertinib Trumps Osimertinib in EGFR-Positive NSCLC

The combination of amivantamab-vmjw (Rybrevant) and lazertinib (Leclaza) elicited greater progression-free survival (PFS) and duration of response (DOR) in the frontline when compared with osimertinib (Tagrisso) for patients with EGFR-mutated non–small cell lung cancer (NSCLC). These findings come from the phase 3, international, randomized MARIPOSA trial (NCT04487080), in which investigators randomly assigned patients 2:2:1 to receive either amivantamab-lazertinib, osimertinib alone, or lazertinib alone. Unfortunately, there were some patients from the amivantamab/lazertinib and osimertinib arms that discontinued treatment because of treatment-related adverse events (AEs).

“With the addition of amivantamab, which is a bispecific EGFR/MET antibody, we expected and did have more AEs. Of course, the AEs did have to be managed. The typical AEs are rash, cutaneous reactions, and immune-related AEs. The most concerning thing over time are not the immune-related reactions, because that’s typically [observed with] the first dose,” Alexander Spira, MD, PhD, director of the Virginia Cancer Specialists Research Institute and investigator on the MARIPOSA trial, told Targeted Oncology^TM in an interview.

Breakthroughs in Lung Cancer Treatment Presented at ASCO Explained

In this article, Aakash Desai, MD, MPH, explains the current breakthroughs presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting regarding lung cancer treatment. Desai highlights data from the PACIFIC (NCT02125461), LAURA (NCT03521154), and CROWN (NCT03052608) trials, in which targeted therapies for patients with oncogene-driven NSCLC were used. He also explains the promising data from the ADRIATIC study (NCT03703297) for small cell lung cancer (SCLC) and the needs left unanswered from the EVOKE-01 study (NCT05089734) for those with refractory or relapsed disease after immunotherapy or chemotherapy.

“We also saw median overall survival [OS] benefit with durvalumab at 55 months vs 33 with placebo. I think this is an important advance, especially for [SCLC], which is a very difficult-to-treat disease and an aggressive disease. For those patients with limited-stage SCLC, the option of incorporating immunotherapy and the outcomes and efficacy that we see is exciting, and I definitely will use it in the clinic once it is approved,” Desai said.Desai is thoracic and phase 1 medical oncologist and assistant professor at the O’Neal Cancer Center at the University of Alabama, Birmingham.

Exploring Immunotherapy Combinations Based on PD-L1 Expression in NSCLC

In the first installment of this 2-part series, John V. Heymach, MD, PhD, discusses the use of immunotherapy combinations based on PD-L1 expression in a 62-year-old patient with NSCLC. In the discussion, he highlights data from the KEYNOTE-407 (NCT02775435) and CheckMate 9LA (NCT03215706) trials and provides valuable insights regarding FDA drug approvals and how he administers certain combinations for specific patient populations.

“When your patient has negative PD-L1 expression, the DOR to PD-1 inhibitor monotherapy tends to be much shorter. That’s part of the reason I tend to go towards dual immunotherapy at some point in patients with the PD-L1 expression less than 1%, but you certainly could use monotherapy,” Heymach said in the discussion for the Case-Based Roundtable® event. Heymach is professor in the Department of Cancer Biology and David Bruton, Jr Chair in Cancer Research Chair in the Department of Thoracic/Head and Neck Medical Oncology Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center in Houston, Texas.

Nivolumab Delivers Improved PFS and ORR in Uterine and Ovarian Cancers

Nivolumab (Opdivo) elicited promising PFS and overall response rates in a single arm, phase 2 trial (NCT03241745) for those with mismatch repair deficiency (dMMR) in uterine or ovarian cancers, meeting its coprimary end points. Treatment options with PD-1 inhibitors for dMMR gynecologic cancers are limited, which led to the evaluation of nivolumab’s safety and efficacy for this patient demographic.

In the study, nivolumab was given once every 4 weeks at a dose of 480 mg and treatment continued until either disease progression or development of unacceptable toxicity. Enrolled patients had a histologically confirmed diagnosis of metastatic or recurrent uterine cancer, including endometrial carcinoma, carcinosarcoma, clear cell carcinoma, leiomyosarcoma, undifferentiated sarcoma, and high-grade endometrial stromal sarcoma. Secondary end points were OS, disease control rate (DCR), DOR, and safety. In addition, there were exploratory end points that evaluated biomarkers and molecular correlates of response.

Approval Request Submitted for Curium’s Lutetium Lu 177 SSTR+ GEP-NETs

A 505(b)(2) request for FDA approval has been submitted for Curium’s formulation of lutetium Lu 177 (Lutathera) dotatate injection for the treatment of somatostatin receptor (SSTR)-positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs).The agent has demonstrated improved PFS when compared with high-dose octreotide in the NETTER-1 trial (NCT01578239). The Novartis company, Advanced Accelerator Applications, gained approval for the agent in January 2018 for the treatment of adult patients with SSTR-positive GEP-NETs, including foregut, midgut, and hindgut NETs.

“Curium’s 505(b)(2) NDA for lutetium Lu 177 dotatate injection marks another important milestone for Curium in its evolution to bring new tools for patients and health care providers to both diagnose and now potentially treat disease,” said Michael Patterson, chief executive officer of Curium North America, in a press release. “Nuclear medicine-based cancer therapies must continue to be more widely and reliably available for patients and their caregivers.”

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

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