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

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P2, N=0, Withdrawn, Erasmus Medical Center | N=60 --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 Withdrawn | Trial primary completion date: Feb 2025 --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P1/2, N=92, Terminated, Gilead Sciences | Withdrawn --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.

P1, N=410, Recruiting, Seagen Inc. | Not yet recruiting --> Recruiting

P1, N=266, Active, not recruiting, Sanofi | Trial completion date: Aug 2023 --> Feb 2024

Despite the negative results of rovalpituzumab tesirine (Rova-T), other ADCs targeting different antigens, such as B7-H3, seizure-related homolog 6 (SEZ6), and CEACAM5, have also been investigated in clinical trials, including for SCLC, and their results suggest preliminary activity, either alone or in combination with other therapies. More recently, sacituzumab govitecan, an anti-TROP2 ADC, demonstrated promising activity in lung cancer, including SCLC. Furthermore, an anti-B7-H3 (CD276), ifinatamab deruxtecan (DS7300A), showed a high response rate and durable responses in heavily pretreated SCLC...Further studies are needed to determine their efficacy and safety and the best location in the treatment algorithm for SCLC. In this review, we aim to collect and describe the results regarding the past, the present, and the future of ADCs in SCLC.

P2, N=215, Recruiting, Sanofi | Trial primary completion date: May 2024 --> Sep 2024

P1, N=410, Not yet recruiting, Seagen Inc.

P3, N=450, Recruiting, Sanofi | Trial completion date: Aug 2024 --> Aug 2025 | Trial primary completion date: Jul 2024 --> Jul 2025

No abstract available

P2, N=215, Recruiting, Sanofi | N=120 --> 215

P1, N=84, Recruiting, EDDC (Experimental Drug Development Centre), A*STAR Research Entities | Trial completion date: May 2025 --> Jun 2026 | Trial primary completion date: Apr 2025 --> Jun 2026

In NSQ-NSCLC tumors, CEACAM5 HE prevalence was 24.3% overall and was higher with KRAS altered and with PD-L1 negative/low tumors but similar regardless of EGFR mutation status. These findings support targeting CEACAM5 and the clinical development of tusamitamab ravtansine for patients with NSQ-NSCLC with CEACAM5 HE.

P1, N=56, Active, not recruiting, Sanofi | Recruiting --> Active, not recruiting | Trial completion date: Dec 2024 --> Aug 2024 | Trial primary completion date: Nov 2023 --> Aug 2023

P2, N=43, Recruiting, Sanofi | Trial primary completion date: Sep 2024 --> Dec 2024

(NCT02187848). The collective results of this phase I dose-escalation study will inform further studies of tusamitamab ravtansine in patients with solid tumors with CEACAM5 expression, including patients with non-small cell lung cancer.

Further validation is warranted in terms of protein expression. Our results underscore the potential value of gene expression profiling to identify new targets and improve patient selection in the context of NSCLC-BM ADC therapy.

Docetaxel ± ramucirumab (ram) every 3 weeks is standard second-line therapy for mNSQ NSCLC without targetable mutations after progression on immunotherapy ± chemotherapy. Conclusions Tusa rav + ram showed encouraging efficacy. The safety of this combination was consistent with the safety profile of each drug, with no unexpected safety signals.

In this review, we discuss the available evidence and future perspectives on ADCs for lung cancer treatment, including a comprehensive discussion on structure-based drug design, mechanism of action, and resistance concepts. Data were summarized by specific target antigen, biology, efficacy, and safety, differing among ADCs according to the ADC payload and their pharmacokinetics and pharmacodynamics properties.

Trastuzumab Deruxtecan (also known as DS-8201a or T-DXd) an ADC directed at HER2 recently became the first ADC to receive FDA approval in lung cancer, on the basis of its activity in tumors with HER2 mutations, demonstrated in the Destiny-Lung01 and Lung02 trials. PRACTICAL APPLICATIONS: Traztuzumab deruxtecan (T-DXd) is the first antibody-drug conjugate (ADC) approved for lung cancer on the basis of activity in patients with HER2 mutation–positive non–small-cell lung cancer demonstrated in the DESTINY-Lung01 and DESTINY-Lung02 trials.ADCs directed at additional targets, including TROP-2, HER3, MET, CEACAM5, and DLL2, are being clinically evaluated in a range of settings as monotherapy and in combination with other agents including immunotherapy.Although ADCs will likely become established as additional treatment options for lung cancer, there remains a need to develop strategies for optimal patient selection and to overcome resistance to treatment.

P1, N=84, Recruiting, EDDC (Experimental Drug Development Centre), A*STAR Research Entities | Not yet recruiting --> Recruiting

P2, N=130, Not yet recruiting, Innovent Biologics (Suzhou) Co. Ltd.

P2, N=43, Recruiting, Sanofi | Trial primary completion date: Apr 2023 --> Aug 2024

P2, N=38, Recruiting, Sanofi | Trial completion date: May 2024 --> Sep 2024 | Trial primary completion date: Feb 2024 --> Sep 2024

Sponsored by Sanofi. Join us for an overview of Sanofi’s oncology pipeline with a focus on tusamitamab ravtansine (SAR408701), an ADC selectively targeting CEACAM5-expression tumors with promising antitumor activity and a favorable safety profile in heavily pretreated patients with CEACAM5 positive advanced NSQ NSCLC.

No abstract available

P2, N=34, Active, not recruiting, Sanofi | Trial completion date: Aug 2023 --> Nov 2023