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

Safety, pharmacokinetics, and antitumor activity of the anti-CEACAM5-DM4 antibody-drug conjugate tusamitamab ravtansine (SAR408701) in patients with advanced solid tumors: First-in-human dose-escalation study. (PubMed, Ann Oncol) - "Tusamitamab ravtansine had a favorable safety profile with reversible, dose-related keratopathy as the DLT. Based on the overall safety profile, pharmacokinetic data, and Bayesian model recommendations, the maximum tolerated dose of tusamitamab ravtansine was defined as 100 mg/m Q2W."

Clinical • Journal • P1 data • PK/PD data • Oncology • Ophthalmology • Solid Tumor • CEACAM5

Tusamitamab Ravtansine vs Docetaxel in Previously Treated Advanced Nonsquamous NSCLC: Results from Phase 3 CARMEN-LC03 Trial (IASLC-WCLC 2024) - P3 | "Despite trends favoring tusa rav on interim OS and electronic patient reported outcomes analysis, study did not meet dual primary endpoint on improving the PFS per central review; likely due to unanticipated higher median PFS and OS with docetaxel. Tusa rav had better safety in various important clinical categories."

Metastases • P3 data • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CEACAM5

Safety and efficacy of tusamitamab ravtansine in combination with pembrolizumab ± chemotherapy in patients with CEACAM5-positive nonsquamous NSCLC (CARMEN-LC05 phase 2 study) (ELCC 2023) - P2 | "Methods CARMEN-LC05 assessed safety and antitumor activity of tusa rav in combination with SoC regimens: with pembro [T2]; with pembro + platinum-based chemotherapy (pCT) [T3]; and with pembro + pCT + pemetrexed [T4] in patients with advanced/metastatic NSQ NSCLC with CEACAM5 intensity of ≥2+ in ≥1% of tumor cells by immunohistochemistry. Objective response rate (ORR) and disease control rate (DCR) for all patients were 40% and 88%, respectively. Table: 13MO Conclusions Tusa rav combined with SoC showed encouraging antitumor activity across all treatment arms with a favorable safety profile, including in the T4 arm, and no new safety concerns, supporting ongoing evaluation of tusa rav."

Clinical • Combination therapy • P2 data • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • BRAF • CEACAM5 • EGFR

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 (CARMEN-LC05) (clinicaltrials.gov) - P2 | N=215 | Recruiting | Sponsor: Sanofi | Trial primary completion date: May 2024 ➔ Sep 2024

Combination therapy • Metastases • Trial primary completion date • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CEACAM5

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 (CARMEN-LC05) (clinicaltrials.gov) - P2 | N=120 | Recruiting | Sponsor: Sanofi | Trial completion date: Nov 2023 ➔ Aug 2024 | Trial primary completion date: Aug 2022 ➔ Jul 2023

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

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 (CARMEN-LC05) (clinicaltrials.gov) - P2 | N=215 | Recruiting | Sponsor: Sanofi | N=120 ➔ 215

Combination therapy • Enrollment change • Metastases • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CEACAM5

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 (CARMEN-LC05) (clinicaltrials.gov) - P2 | N=120 | Recruiting | Sponsor: Sanofi | Trial completion date: Aug 2024 ➔ Mar 2025 | Trial primary completion date: Jul 2023 ➔ Mar 2024

Combination therapy • Trial completion date • Trial primary completion date • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • 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 | 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

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."

ADC • 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

Tusamitamab ravtansine induces immunogenic cell death and synergizes with anti-PD-1 or anti-PD-L1 antibody combination in solid tumor (AACR 2024) - "It is currently being evaluated in patients with advanced CEACAM5-positive NSQ NSCLC, in a phase II study in combination with pembrolizumab, and a phase III trial as single agent in comparison with docetaxel. In this model, the combination of tusamitamab ravtansine with anti-PD-1 or anti-PD-L1 antibody led to complete response and, even, tumor-free survivors at 120 days post tumor implantation while single agents were inactive or transiently active. In summary, these preclinical data show that tusamitamab ravtansine could be beneficially combined with immune checkpoint and strongly support their evaluation in clinical development."

Immunogenic cell death • IO biomarker • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CALR • CD8 • CEACAM5 • HMGB1 • IL6

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"

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

The Landscape of CEACAM5 Expression by Immunohistochemistry in NSCLC. (PubMed, JTO Clin Res Rep) - "We assessed CEACAM5 protein expression by immunohistochemistry in two separate cohorts of patients with NSCLC to include both routine clinical biopsy and resection specimens, using the anti-CEACAM5 clone 769 antibody assay protocol and scoring scheme for the tusamitamab ravtansine clinical trials...There was no prognostic effect of CEACAM5 expression on recurrence-free survival or overall survival. Our data revealed that 18% of routinely diagnosed clinical NSCLC samples had high CEACAM5 expression by immunohistochemistry, and its expression was not associated with oncogenic driver mutations or patient prognosis in a predominantly early stage NSCLC cohort."

IO biomarker • Journal • Tumor mutational burden • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CEACAM5 • EGFR • KRAS • PD-L1 • TMB

Novel Drug-Disease Modeling Framework for Oncology Benefit-Risk Evaluation: Application to Tusamitamab Ravtansine. (PubMed, CPT Pharmacometrics Syst Pharmacol) - "These findings demonstrate how early-phase data can inform optimal dose selection by quantifying benefit-risk. This robust framework and methodology is generalizable beyond Tusa, offering value to support dose selection and trial decision-making in oncology drug development."

Benefit-risk assessment • Journal • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CEACAM5

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

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

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