Advancing Lung Cancer Treatment With Bispecific Antibodies: A Review of Amivantamab and Tarlatamab

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Bispecific antibodies (BsAbs) are a class of antibodies that can bind to 2 different sites at the same time. They are a type of next-generation monoclonal antibody (mAb) but, unlike typical mAbs that target only 1 antigen, BsAbs can cause multiple physiological or anti-tumor responses. Because of the ability to target more than 1 site, BsAbs are proving to be a deeper and more durable treatment option. Currently, there are more than 100 BsAbs in clinical development, most being in the early stages.¹

During the 2024 Florida Society of Clinical Oncology Fall Session in Orlando, Elizabeth Osmon, PharmD, BCPS, BCOP, a medical oncology clinical pharmacy specialist at Memorial Healthcare System, presented a review of BsAbs for lung cancer. In this review, Osmon discussed 2 BsAbs: amivantamab (Rybrevant; Janssen Pharmaceutical Companies) for non–small cell lung cancer (NSCLC) and tarlatamab (Imdelltra; Amgen) for small cell lung cancer (SCLC).

Amivantamab

Amivantamab is a BsAb that binds to receptors on cancer cells for proteins EGF and MET; this prevents the activation of signaling pathways that promote tumor cell growth. Amivantamab is FDA approved:

• in combination with lazertinib (Lazcluze; Janssen Biotech, Inc) for the first-line treatment of adult patients with locally advanced or metastatic NSCLC with EGFR exon 19 deletion (Ex19del) or exon 21 L858R substitution mutations;
• in combination with carboplatin and pemetrexed for the treatment of adult patients with locally advanced or metastatic NSCLC with EGFR Ex19del or exon 21 L858R substitution mutations whose disease has progressed on or after treatment with an EGFR tyrosine kinase inhibitor;
• in combination with carboplatin and pemetrexed for the first-line treatment of adult patients with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations; and as a single agent for the treatment of adult patients with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations whose disease has progressed on or after platinum-based chemotherapy.

The approval was based on the results of the phase 3 MARIPOSA trial (NCT04487080), which randomly assigned more than 1000 patients to amivantamab in combination with lazertinib, lazertinib, or osimertinib (Tagrisso; AstraZeneca). The median progression-free survival (PFS) was significantly longer in the amivantamab/lazertinib group than in the osimertinib group (23.7 vs 16.6 months). The median response duration was 25.8 months and 16.8 months, respectively. In a planned interim overall survival (OS) analysis of amivantamab plus lazertinib compared with osimertinib, the HR for death was 0.80.²

Adverse events (AEs) include infusion-related reactions, elevated hepatic enzymes, fatigue, musculoskeletal pain, infection, stomatitis, edema, and constipation. Amivantamab is dosed based on weight and is administered weekly via a peripheral line on week 1 and week 2 to reduce the risk of infusion-related reactions, and with the initial dose as a split infusion on week 1 on days 1 and 2.³

Tarlatamab

Tarlatamab is a BsAb immunotherapy drug used to treat SCLC. Tarlatamab binds to tumor cells and T cells, helping the T cells recognize and destroy cancer cells. It targets the protein DLL3 on the surface of tumor cells and CD3 on T cells.

The FDA approval was based on results of the DeLLphi-301 trial (NCT05060016), which enrolled 220 patients who had previously received a median of 2 lines of prior treatment. At 10 months, a 40% objective response rate was observed. The median duration of response was shown to be 9.7 months, with 68% of those who responded still on therapy at 6 months and 40% at more than 12 months.⁴

The dosing is 1 mg intravenous (IV) on cycle 1, day 1, followed by 10 mg IV on cycle 1, days 8 and 15. For all subsequent cycles, administer tarlatamab 10 mg IV on days 1 and 15, every 28 days until disease progression or unacceptable toxicity. However, it is important to monitor patients in an appropriate health care setting for 22 to 24 hours after the start of the tarlatamab infusion on cycle 1, days 1 and 8. It is recommended that patients stay with a caregiver within 1 hour of an appropriate health care setting, for a total of 48 hours from the start of the tarlatamab infusion on cycle 1, days 1 and 8. Common AEs include cytokine release syndrome, fatigue, elevated hepatic enzymes, neurotoxicity, fever, and dysgeusia.⁵

Considering that SCLC can be a very aggressive disease with a limited PFS, shortened duration of response, and OS in subsequent lines of therapy, this treatment holds promise for these patients.

REFERENCES

1. Bispecific antibodies: an area of research and clinical applications. FDA. February 14, 2024. Accessed November 11, 2024. https://www.fda.gov/drugs/spotlight-cder-science/bispecific-antibodies-area-research-and-clinical-applications

2. Cho BC, Lu S, Felip E, et al; MARIPOSA Investigators. Amivantamab plus lazertinib in previously untreated EGFR-mutated advanced NSCLC. N Engl J Med. 2024;391(16):1486-1498. doi:10.1056/NEJMoa2403614

3. Rybrevant. Prescribing information. Janssen Biotech Inc; 2021. Accessed November 11, 2024. https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/761210s000lbl.pdf

4. Ahn MJ, Cho BC, Felip E, et al; DeLLphi-301 Investigators. Tarlatamab for patients with previously treated small-cell lung cancer. N Engl J Med. 2023;389(22):2063-2075. doi:10.1056/NEJMoa2307980

5. Imdelltra. Prescribing information. Amgen Inc; 2024. Accessed November 11, 2024. https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/761344s000lbl.pdf