P1/2, N=250, Recruiting, EMD Serono Research & Development Institute, Inc. | Not yet recruiting --> Recruiting

P1, N=410, Recruiting, Seagen Inc. | Trial primary completion date: Mar 2029 --> Mar 2030

P1, N=24, Recruiting, Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany

P2, N=57, Terminated, Sanofi | Active, not recruiting --> Terminated; Sponsor decision, the decision is not related to any safety concern.

P2, N=35, Terminated, Sanofi | Active, not recruiting --> Terminated; Sponsor decision, the decision is not related to any safety concern.

P2, N=35, Terminated, Sanofi | Active, not recruiting --> Terminated; Sponsor decision, the decision is not related to any safety concern.

P2, N=22, Terminated, Sanofi | Active, not recruiting --> Terminated; Sponsor decision, the decision is not related to any safety concern.

P2, N=35, Active, not recruiting, Sanofi | Trial completion date: Jun 2024 --> Dec 2024

Antibody Drug Conjugates (ADCs) are a novel class of therapeutics that structurally are composed by an antibody directed to a tumour epitope connected via a linker to a cytotoxic payload, and that have shown significant antitumor activity across a range of malignancies including lung cancer. In this article we review the pharmacology and design of ADCs, as well as we describe the results of different studies evaluating ADCs in lung cancer directed to several targets including HER2, HER3, TROP2, MET, CEACAM5 and DLL3, among others.

P1/2, N=250, Not yet recruiting, EMD Serono Research & Development Institute, Inc.

P1, N=254, Terminated, Sanofi | Active, not recruiting --> Terminated; Sponsor decision, The decision is not related to any safety concern.

P2, N=31, Terminated, Sanofi | Active, not recruiting --> Terminated; Sponsor decision, the decision is not related to any safety concern.

P3, N=389, Active, not recruiting, Sanofi | Trial completion date: Aug 2026 --> Jun 2025

The antibody-drug conjugate tusamitamab ravtansine specifically recognizes the A3-B3 domains of human CEACAM5 (hCEACAM5)...The cryogenic electron microscopy structure of the hCEACAM5A3-B3- tusa Fab complex (3.11 Å overall resolution) reveals a discontinuous epitope involving residues in the A3-B3 domains and an N-linked mannose at residue Asn612. Conformational constraints on the epitope-paratope interface enable tusamitamab to target hCEACAM5A3-B3 and distinguish CEACAM5 from other CEACAMs.

P2, N=22, Active, not recruiting, Sanofi | Trial completion date: Sep 2024 --> Dec 2024

P1, N=21, Recruiting, BeiGene | Not yet recruiting --> Recruiting

P1, N=21, Not yet recruiting, BeiGene

P2, N=4, Terminated, Innovent Biologics (Suzhou) Co. Ltd. | N=130 --> 4 | Trial completion date: Dec 2025 --> Dec 2023 | Not yet recruiting --> Terminated | Trial primary completion date: Apr 2024 --> Nov 2023; strategy terminates development, the decision is not due to any safety-related issues

P2, N=50, Active, not recruiting, Sanofi | Trial primary completion date: Aug 2024 --> Feb 2024

P2, N=22, Active, not recruiting, Sanofi | Trial completion date: May 2024 --> Sep 2024

[89Zr]Zr-DFO-labetuzumab imaging was able to clearly delineate both neuroendocrine H660 xenografts and AR- DU145 in vivo but could not detect the AR-positive xenograft LNCaP. Immuno-PET imaging with [89Zr]Zr-DFO-labetuzumab is a promising diagnostic tool for AR- prostate cancer.

Several ADCs have already been approved for other cancers, such as breast cancer and urothelial carcinoma. This review summarizes the knowledge about the efficacy and tolerance profiles of ADCs targeting TROP2, HER2, HER3, CEACAM5 and c-MET in metastatic NSCLC with and without alterations in oncogenic drivers.

Overall, 73.1% (49/67) of cervical cancer samples are CD138-positive with 38.8% (26/67) of cervical cancer samples showing at least moderate or high expression. (4) TROP2, CEACAM5 or CD138 do seem suitable for further clinical research and the data presented here might be used to guide further clinical trials with ADCs in advanced and recurrent cervical cancer patients.

P2, N=50, Active, not recruiting, Sanofi | Trial primary completion date: Apr 2024 --> Aug 2024

P2, N=31, Active, not recruiting, Sanofi | Trial completion date: Mar 2024 --> Sep 2024

We assessed the expression of CEACAM5 by IHC on clinical biopsy/resection samples of consecutively diagnosed NSCLC from September 2022 to June 2023 at our institution, using the anti-CEACAM5 clone 769 antibody assay protocol developed for tusamitamab ravtansine clinical trials... Our data showed that approximately 20% of routinely diagnosed clinical NSCLC samples had high CEACAM5 expression by IHC. The interrater reliability on the determination of high CEACAM5 expression was moderate among the three pathologists. We highlighted the challenging aspects in the evaluation of this biomarker.

P1, N=56, Terminated, Sanofi | Trial completion date: Aug 2024 --> Mar 2024 | Active, not recruiting --> Terminated; Tusamitamab ravtansine clinical development program is discontinued as CARMEN-LC03 trial did not meet dual primary endpoint of improving progression-free survival. The decision is not related to any safety concern.

P1, N=180, Recruiting, EMD Serono Research & Development Institute, Inc. | Trial completion date: May 2025 --> Feb 2026 | Trial primary completion date: Apr 2024 --> Feb 2026

P1, N=180, Recruiting, EMD Serono Research & Development Institute, Inc. | N=31 --> 180 | Trial completion date: Nov 2023 --> May 2025 | Trial primary completion date: Nov 2023 --> Apr 2024

P2, N=0, Withdrawn, Erasmus Medical Center | N=60 --> 0 | Trial completion date: May 2025 --> Feb 2024 | Not yet recruiting --> Withdrawn | Trial primary completion date: Feb 2025 --> Feb 2024

P1, N=254, Active, not recruiting, Sanofi | Trial completion date: Feb 2024 --> Aug 2024

P2, N=22, Active, not recruiting, Sanofi | Recruiting --> Active, not recruiting | N=38 --> 22 | Trial completion date: Dec 2024 --> May 2024 | Trial primary completion date: Dec 2024 --> Jan 2024

P2, N=57, Active, not recruiting, Sanofi | Recruiting --> Active, not recruiting

P2, N=31, Active, not recruiting, Sanofi | Recruiting --> Active, not recruiting

P2, N=50, Active, not recruiting, Sanofi | Recruiting --> Active, not recruiting

P3, N=411, Active, not recruiting, Sanofi | Recruiting --> Active, not recruiting

P1/2, N=92, Terminated, Gilead Sciences | Withdrawn --> Terminated

These data suggest that further preclinical and clinical development of CT109-SN-38 is warranted.

P2, N=35, Active, not recruiting, Sanofi | Trial completion date: Oct 2023 --> Jun 2024

P2, N=94, Recruiting, Sanofi | Trial completion date: Jan 2025 --> Aug 2025 | Trial primary completion date: Jul 2024 --> Dec 2024

In BxPC-3 and MKN-45 xenograft mice, administration of UdADC B9-MMAE (5 mg/kg, i.v.) every 2 days for 4 times markedly inhibited the tumor growth without significant change in body weight. This study may have significant implications for the design of next-generation ADCs.

Promising initial evidence demonstrates the potential of targeting CEACAM5 to provide additional therapeutic options for patients with lung cancer, and several ongoing clinical trials are evaluating CEACAM5-targeting agents across different settings in NSCLC.In this live satellite symposium, renowned experts will discuss the clinical rationale for targeting CEACAM5, explore how strategies to test for CEACAM5 fit into larger testing paradigms in NSCLC, and review ongoing research efforts to develop antibody-drug conjugates—including novel CEACAM5-directed therapies—for the treatment of advanced NSCLC. These discussions will be supplemented by instructive animations that will help to explain these complicated concepts more simply.