tusamitamab ravtansine (SAR408701) / Sanofi, Innovent Biologics, AbbVie - LARVOL DELTA

Biomarker analysis from a Phase 1/1b study of tusamitamab ravtansine in patients with advanced non-small cell lung cancer. (PubMed, Transl Oncol) - P1 | "In CEACAM5 HE, the ORR was greater with high versus low cCEA. Associations were observed between cCEA and cCEACAM5; IHC CEACAM5, cCEA, and cCEACAM5; IHC CEACAM5 and CEACAM5 mRNA, but not between IHC CEACAM5 and oncogenic drivers."

Biomarker • Journal • P1 data • Embryonal Tumor • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CEACAM5 • EGFR • KRAS

CARMEN-BT01: Tusamitamab Ravtansine Monotherapy and in Combination in Patients With CEACAM5-positive Advanced Solid Tumors (clinicaltrials.gov) - P2 | N=50 | Terminated | Sponsor: Sanofi | Completed ➔ Terminated; Sponsor decision, the decision is not related to any safety concern.

Monotherapy • Trial termination • Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • Triple Negative Breast Cancer

Evaluation of the Safety, Pharmacokinetics, and Antitumor Activity of Tusamitamab Ravtansine in Patients With Nonsquamous NSCLC With High or Moderate Expression of Carcinoembryonic Antigen-Related Cell Adhesion Molecule 5. (PubMed, JTO Clin Res Rep) - P1 | "Corneal AEs occurred in 38.0% (35/92), typically grade 1/2, reversible, and manageable by dose modifications. Tusamitamab ravtansine demonstrated a favorable safety profile, objective responses, and antitumor activity in patients with high CEACAM5-expressing NSq NSCLC."

Journal • PK/PD data • Keratitis • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Ocular Inflammation • Oncology • Ophthalmology • Pulmonary Disease • Solid Tumor • CEACAM5

Prognostic Impact of Carcinoembryonic Antigen-Related Cell Adhesion Molecule 5 Expression in Non-Small Cell Lung Cancer (IASLC-WCLC 2025) - "Methods : We retrospectively evaluated CEACAM5 expression by IHC on resected NSCLC specimens from 2005 to 2012 at our institution, using the anti-CEACAM5 clone 769 antibody assay protocol developed for the tusamitamab ravtansine clinical trials...High CEACAM5 expression was not associated with tumor stage (p=0.4), RFS (p=0.8), or OS (p=0.7). Conclusions : In our cohort of predominantly early-stage resected NSCLC including adenocarcinoma and squamous cell carcinoma, we did not observe a significant prognostic impact of CEACAM5 expression on RFS or OS."

IO biomarker • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • CEACAM5 • EGFR • KRAS

Antibody-Drug Conjugates Versus Docetaxel for Previously Treated Advanced NSCLC: Systematic Review and Meta-Analysis of RCTs (IASLC-WCLC 2025) - "Methods : Databases [PubMed (MEDLINE), EMBASE and Cochrane Library], clinical trial registries, and proceedings of global oncology conferences from January 2015 to November 2024 were screened for phase II/III RCTs comparing ADC (e.g., sacituzumab govitecan, datopotamab deruxtecan, and tusamitamab ravtansine) versus docetaxel. Conclusions : Our findings report a significant survival benefit in patients with non-squamous NSCLC treated with ADCs compared to docetaxel with a manageable safety profile. However, further research is needed to address heterogeneity, refine patient selection and obtain more mature survival data with predictive biomarkers."

IO biomarker • Metastases • Retrospective data • Review • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Solid Tumor

CARMEN-LC03: SAR408701 Versus Docetaxel in Previously Treated, Carcinoembryonic Antigen-related Cell Adhesion Molecule 5 (CEACAM5) Positive Metastatic Non-squamous Non-small-cell Lung Cancer Patients (clinicaltrials.gov) - P3 | N=389 | Active, not recruiting | Sponsor: Sanofi | Trial completion date: Jun 2025 ➔ Mar 2026

Trial completion date • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CEACAM5

Innovative Peptide Therapeutics in the Pipeline: Transforming Cancer Detection and Treatment. (PubMed, Int J Mol Sci) - "Innovative peptide platforms now enable three transformative applications: (1) precision molecular diagnostics (e.g., 18F-PSMA-1007 for prostate cancer detection), (2) targeted therapies (e.g., BT5528 and SAR408701 targeting tumour-specific antigens), and (3) theranostic systems (e.g., RAYZ-8009 and 177Lu-FAP-2286 integrating imaging and radiotherapy). By overcoming current limitations, peptide drugs are poised to redefine cancer management, offering safer, more effective alternatives to conventional therapies. Their integration into clinical practice could mark a critical milestone in achieving precision oncology."

IO biomarker • Journal • Review • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Phase 1 study evaluating safety and pharmacokinetics of tusamitamab ravtansine monotherapy in Japanese patients with advanced malignant solid tumors. (PubMed, Int J Clin Oncol) - "Tusamitamab ravtansine demonstrated a tolerable safety profile at a dose of 80-170 mg/m2 in three different administration schedules in Japanese adults with metastatic solid tumors."

Journal • Monotherapy • P1 data • PK/PD data • Gastroenterology • Gastrointestinal Disorder • Oncology • Solid Tumor • CEACAM5

Multimodal cancer therapy consisting of antibody-drug conjugates and radiotherapy in cancer treatment (AACR 2025) - "Accordingly, combination of RT with ADCs targeting HER2: trastuzumab emtansine/deruxtecan/duocarmazine (T-DM1/T-DXd/T-Duo) and disitamab vedotin, TROP2: datopotamab deruxtecan and sacituzumab govitecan, EGFR: depatuxizumab MMAE, HER3: patritumab deruxtecan, Nectin4: enfortumab vedotin and CEACAM5: tusamitamab ravtansine were evaluated. Together, this study demonstrates that inherent sensitivity of tumor cells to different payload classes, DAR and TAA dynamic are of relevance for the efficacy of ADC. Informed selection of ADC exhibited synergistic effects with RT providing a novel multimodal and promising strategy for efficient cancer eradication."

Breast Cancer • Gastric Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor • Squamous Cell Carcinoma • CEACAM5 • EGFR • ERBB3 • HER-2 • NECTIN4

Diffuse interstitial lung disease induced by antibody-drug conjugates (PubMed, Rev Mal Respir) - "Among the many ADCs being developed, several can cause ILD of varying grades and intensity. Knowledge of their risks, diagnostic and therapeutic modalities is required in order to quickly detect and treat ADC-induced ILD."

Journal • Review • Interstitial Lung Disease • Lung Cancer • Nephrology • Non Small Cell Lung Cancer • Oncology • Pulmonary Disease • Renal Disease • Respiratory Diseases • Solid Tumor • CEACAM5 • ERBB3 • HER-2 • MET

Evaluation of the safety, pharmacokinetics, and antitumor activity of tusamitamab ravtansine in patients with nonsquamous non-small cell lung cancer with high or moderate expression of carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) (JTO Clinical and Research Reports) - P1 | N=254 | NCT02187848 | Sponsor: Sanofi | "Sixty-four patients with high and 28 with moderate CEACAM5 expression received a median of 8.0 (1–69) and 4.5 (1–38) treatment cycles, respectively. High expressors had 13 confirmed partial responses (PR) and 28 stable diseases (SD) (objective response rate [ORR], 20.3%; 95% CI: 12.3%–31.7%, P<0.0001); median duration of response was 6.7 months, and median time to progression was 3.7 months (95% CI: 2.7–5.1 months). Moderate expressors had 2 confirmed PR (ORR 7.1%; 95% CI: 2.0%–22.7%, P=0.4117) and 15 SD."

P1 data • Non Small Cell Lung Cancer

SAR408701: An anti-CEACAM5-maytansinoid antibody-drug conjugate to treat CEACAM5-positive neuroendocrine prostate cancer (NEPC) (AACR 2025) - P=N/A | "NEPC is rare de-novo (<1% of the cases) but can represent 15 to 20% of cases after failure of the treatment targeting the androgen receptor (AR) axis (such as enzalutamide, abiraterone) in. Overall, these results demonstrate the efficacy and specificity of SAR408701 against NEPC tumors harboring CEACAM5.This study provides preclinical evidence of the antitumor activity of SAR408701 in CEACAM5-positive NEPC.Funding: Gustave Roussy, Cancer Campus, Grand Paris"

Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Neuroendocrine Tumor • Oncology • Prostate Cancer • Solid Tumor • CEACAM5 • SYP

CARMEN-BT01: Tusamitamab Ravtansine Monotherapy and in Combination in Patients With CEACAM5-positive Advanced Solid Tumors (clinicaltrials.gov) - P2 | N=50 | Completed | Sponsor: Sanofi | Active, not recruiting ➔ Completed

Trial completion • Breast Cancer • Hepatology • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • Triple Negative Breast Cancer

Evaluation of tusamitamab ravtansine, a CEACAM5-targeting antibody drug conjugate, in non-squamous NSCLC participants with negative or moderate CEACAM5 expression and high circulating CEA: Results from phase II CARMEN-LC06 trial (ELCC 2025) - P2 | "Modest antitumor efficacy was observed in some participants; however, the study was limited by low enrollment. No new safety signals were observed; safety was consistent with other clinical studies. Early termination was due to the sponsor's decision to discontinue the clinical development of tusamitamab ravtansine."

P2 data • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CEACAM5

CARMEN-LC05: Tusamitamab Ravtansine (SAR408701) in Combination With Pembrolizumab and Tusamitamab Ravtansine (SAR408701) in Combination With Pembrolizumab and Platinum-based Chemotherapy With or Without Pemetrexed in Patients With NSQ NSCLC (clinicaltrials.gov) - P2 | N=57 | Terminated | Sponsor: Sanofi | Active, not recruiting ➔ Terminated; Sponsor decision, the decision is not related to any safety concern.

Trial termination • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CEACAM5

CARMEN-GC01: Tusamitamab Ravtansine (SAR408701) in Combination With Ramucirumab in Pretreated Participants With Gastric Cancer (clinicaltrials.gov) - P2 | N=35 | Terminated | Sponsor: Sanofi | Active, not recruiting ➔ Terminated; Sponsor decision, the decision is not related to any safety concern.

Trial termination • Esophageal Cancer • Gastric Adenocarcinoma • Gastric Cancer • Gastroesophageal Cancer • Gastroesophageal Junction Adenocarcinoma • Oncology • Solid Tumor • CEACAM5

Tusamitamab Ravtansine (SAR408701) in Combination With Ramucirumab or Ramucirumab and Pembrolizumab in Pretreated Patients With NSQ NSCLC (CARMEN-LC04) (clinicaltrials.gov) - P2 | N=31 | Terminated | Sponsor: Sanofi | Active, not recruiting ➔ Terminated; Sponsor decision, the decision is not related to any safety concern.

Checkpoint inhibition • Combination therapy • Metastases • Trial termination • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CEACAM5

CARMEN-LC06: Tusamitamab Ravtansine in NSQ NSCLC Participants With Negative or Moderate CEACAM5 Expression Tumors and High Circulating CEA (clinicaltrials.gov) - P2 | N=22 | Terminated | Sponsor: Sanofi | Active, not recruiting ➔ Terminated; Sponsor decision, the decision is not related to any safety concern.

Trial termination • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CEACAM5

CARMEN-GC01: Tusamitamab Ravtansine (SAR408701) in Combination With Ramucirumab in Pretreated Participants With Gastric Cancer (clinicaltrials.gov) - P2 | N=35 | Active, not recruiting | Sponsor: Sanofi | Trial completion date: Jun 2024 ➔ Dec 2024

Combination therapy • Metastases • Trial completion date • Esophageal Cancer • Gastric Adenocarcinoma • Gastric Cancer • Gastroesophageal Cancer • Gastroesophageal Junction Adenocarcinoma • Oncology • Solid Tumor • CEACAM5

CEACAM5: Evaluation of SAR408701 in Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=254 | Terminated | Sponsor: Sanofi | Active, not recruiting ➔ Terminated; Sponsor decision, The decision is not related to any safety concern.

Metastases • Trial termination • Bladder Cancer • Cholangiocarcinoma • Colorectal Cancer • Endometrial Cancer • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Small Cell Lung Cancer • Solid Tumor • CEACAM5

CARMEN-LC03: SAR408701 Versus Docetaxel in Previously Treated, Carcinoembryonic Antigen-related Cell Adhesion Molecule 5 (CEACAM5) Positive Metastatic Non-squamous Non-small-cell Lung Cancer Patients (clinicaltrials.gov) - P3 | N=389 | Active, not recruiting | Sponsor: Sanofi | Trial completion date: Aug 2026 ➔ Jun 2025

Trial completion date • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CEACAM5

Structural insights into epitope-paratope interactions of a monoclonal antibody targeting CEACAM5-expressing tumors. (PubMed, Nat Commun) - "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."

Journal • Oncology • CEACAM5

CARMEN-LC03: Tusamitamab Ravtansine vs Docetaxel in Previously Treated Advanced Nonsquamous NSCLC (THE ASCO POST) - "Dr. Waqar reiterated that the CARMEN-LC03 trial did not meet its primary endpoints of progression-free and overall survival with tusamitamab ravtansine vs docetaxel. 'The docetaxel arm had better progression-free [5.9 vs 2.0-4.2 months] and overall [11.5 vs 5.7-9.6 months] survival than we have seen with historical studies of docetaxel,' she further emphasized."

Media quote

CARMEN-LC06: Tusamitamab Ravtansine in NSQ NSCLC Participants With Negative or Moderate CEACAM5 Expression Tumors and High Circulating CEA (clinicaltrials.gov) - P2 | N=22 | Active, not recruiting | Sponsor: Sanofi | Trial completion date: Sep 2024 ➔ Dec 2024

Trial completion date • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CEACAM5

Phase II, open-label study of frontline tusamitamab ravtansine with pembrolizumab ± chemotherapy in advanced non-squamous non-small cell lung cancer: Updated results from CARMEN-LC05 trial (ESMO 2024) - P2 | "Background: CARMEN-LC05 (NCT04524689), a Phase 2, open-label, non-randomised study, evaluated tusamitamab ravtansine (tusa rav), a CEACAM5-targeting antibody-drug conjugate, in combination with pembrolizumab (pembro) and pembro + platinum-based chemotherapy (pCT) ± pemetrexed in patients (pts) with CEACAM5+ non-squamous non–small-cell lung cancer (NSQ NSCLC). Tusa rav in combination with pembro ± chemotherapy demonstrated encouraging antitumor activity across PD-L1 subgroups and was associated with a favourable safety profile. Table: 1311P 1311P Safety and efficacy"

Clinical • Metastases • P2 data • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CEACAM5 • PD-L1