Telisotuzumab vedotin

Telisotuzumab vedotin (Teliso‐V) is a c‐Met‐directed antibody‐drug conjugate that delivers a cytotoxic microtubule inhibitor monomethyl auristatin E (MMAE) payload to c‐Met‐expressing tumor cells. It received accelerated approval from the US FDA for the treatment of adults with locally advanced or metastatic non‐squamous non‐small cell lung cancer (NSCLC) with high c‐Met protein overexpression (≥ 50% of tumor cells with strong [3+] staining) at a dose of 1.9 mg/kg every 2 weeks (Q2W; maximum 190 mg for patients ≥ 100 kg) as an intravenous infusion. Population pharmacokinetic (PK) modeling used pooled data from a phase 1 ( N  = 35) and phase 2 study ( N  = 269) to describe the Teliso‐V conjugate and unconjugated MMAE PK and evaluate the impact of intrinsic and extrinsic factors on exposures in patients with solid tumors. Body weight, race, albumin, and anti‐drug antibody status were identified as significant covariates on Teliso‐V conjugate clearance, but did not result in clinically meaningful changes in exposure. The exposure‐response evaluations for efficacy (based on the pivotal phase 2 study) showed significant correlations between conjugate exposure and overall response rates. Higher conjugate exposures were also correlated with improved progression‐free survival and overall survival, demonstrating meaningful clinical benefit with the 1.9 mg/kg Q2W dosing regimen. Exposure‐safety evaluations showed significant relationships between conjugate exposures and grade ≥ 2 and grade ≥ 3 peripheral neuropathy, and grade ≥ 2 corneal epitheliopathy. Unconjugated MMAE payload exposures were correlated with a greater probability of grade ≥ 3 treatment‐emergent adverse events. The 1.9 mg/kg Q2W dose maximized efficacy while balancing adverse events in patients with c‐Met overexpressing NSCLC.

The commercial development of antibody therapeutics is a global enterprise involving thousands of biopharmaceutical firms and supporting service organizations. To date, their combined efforts have resulted in over 200 marketed antibody therapeutics and a pipeline of nearly 1,400 investigational product candidates that are undergoing evaluation in clinical studies as treatments for a wide variety of diseases. Here, we discuss key events in antibody therapeutics development that occurred during 2024 and forecast key events related to the late-stage clinical pipeline that may occur in 2025. In particular, we report on 21 antibody therapeutics granted a first approval in at least one country or region during 2024, including bispecific antibodies tarlatamab (IMDELLTRA®), zanidatamab (Ziihera®), zenocutuzumab (BIZENGRI®), odronextamab (Ordspono®), ivonescimab (®), and antibody-drug conjugate (ADC) sacituzumab tirumotecan (®). We also discuss 30 investigational antibody therapeutics for which marketing applications were undergoing review by at least one regulatory agency, as of our last update on December 9, 2024, including ADCs datopotamab deruxtecan, telisotuzumab vedotin, patritumab deruxtecan, trastuzumab botidotin, becotatug vedotin, and trastuzumab rezetecan. Of 178 antibody therapeutics we include in the late-stage pipeline, we summarize key data for 18 for which marketing applications may be submitted by the end of 2025, such as bi- or multispecific antibodies denecimig, sonelokimab, erfonrilimab, and anbenitamab. Key trends in the development and approval of antibody formats such as bispecifics and ADCs, as well as clinical-phase transition and global approval success rates for these antibody formats, are reported.