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

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

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

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

CARMEN-LC03 Fails, but Hope Remains for CEACAM5 Targeting (Medscape) - "Saiama Waqar, MD...who was not involved in the study, underlined that the control arm in the current study 'exceeded expectations.'...Waqar said that tusa rav is 'not ready for prime time but pointed out that CEACAM5 is still being examined as a target in the phase 1/2 study NEO-201, the phase 1 studies PROCEADE-CRC-01 and SGN-CEACAM5C, and the phase 1 trial of EBC-129.'"

Media quote

Exploratory Analyses of Tusamitamab Ravtansine vs Docetaxel in Previously Treated Non-squamous NSCLC Patients: CARMEN-LC03 (IASLC-WCLC 2024) - "Conclusions : These exploratory analyses identify patients likely to derive clinical benefit from tusa rav and suggest a previously unknown prognostic role for CEACAM5 in NSCLC. Additional research is needed to corroborate these findings."

Clinical • IO biomarker • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • 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

PC04. Press Conference (IASLC-WCLC 2024) - "These sessions are open only to registered media who have been credentialed to cover the meeting. OA08.05 - Tusamitamab Ravtansine vs Docetaxel in Previously Treated Advanced Nonsquamous NSCLC: Results from Phase 3 CARMEN-LC03 Trial OA08.03 - Datopotamab Deruxtecan Vs Docetaxel in Patients with Non-Small Cell Lung Cancer: Final Overall Survival from TROPION-Lung01 OA16.03 - Telisotuzumab Vedotin in Asian Patients With c-Met Protein Overexpressing Non-Squamous EGFR WT NSCLC: Results From LUMINOSITY MA13.08 - Exposure Impact on Never-Smoking Lung Cancer Patients MA06.03 - Efficacy and Safety of Taletrectinib in Patients With ROS1+ Non-Small Cell Lung Cancer: The Global TRUST-II Study"

Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR • MET • ROS1

Tusamitamab Ravtansine Misses Survival End Points in Advanced NSCLC Trial (OncLive) - P3 | N=411 | CARMEN-LC03 (NCT04154956) | Sponsor: Sanofi | "In the intent-to-treat (ITT) population, at a median follow-up date of 7.4 months, the PFS per independent review committee (IRC), as part of the final prespecified analysis, was 5.4 months (95% CI, 3.7-7.0) and 5.9 months (95% CI, 5.5-7.4) in the tusamitamab ravtansine (n = 194) and docetaxel (n = 195) arms, respectively (HR, 1.14; 95% CI, 0.86-1.51; P = .8204). At a median follow-up of 18.1 months, the OS during the first interim analysis was 12.8 months (95% CI, 11.8-14.2) and 11.5 months (95% CI, 8.9-15.2) in the respective arms (HR, 0.85; 95% CI, 0.64-1.11; P = .112)."

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

CARMEN-BT01: Tusamitamab Ravtansine Monotherapy and in Combination in Patients With CEACAM5-positive Advanced Solid Tumors (clinicaltrials.gov) - P2 | N=50 | Active, not recruiting | Sponsor: Sanofi | Trial primary completion date: Aug 2024 ➔ Feb 2024

Metastases • Monotherapy • Trial primary completion date • Breast Cancer • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • Triple Negative Breast Cancer

The Study of Tusamitamab Ravtansine (IBI126) Combined With Sintilimab and Tusamitamab Ravtansine (IBI126) Combined With Sintilimab Plus Platinum-based Chemotherapy and Pemetrexed in Subjects With CEACAM5 Positive Expression Advanced/Metastatic Non-squamous Non-small-cell Lung Cancer (NSQ NSCLC) (clinicaltrials.gov) - P2 | N=4 | Terminated | Sponsor: 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

Enrollment change • Metastases • Trial completion date • Trial primary completion date • Trial termination • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • BRAF • CEACAM5

Exploratory Analyses of Tusamitamab Ravtansine vs Docetaxel in Previously Treated Non-squamous NSCLC Patients: CARMEN-LC03 (IASLC-WCLC 2024) - No abstract available

Clinical • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Assessment of carcinoembryonic antigen-related cell adhesion molecule 5 expression by immunohistochemistry in real-world clinical samples of non-small cell lung cancer. (ASCO 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."

Clinical • IO biomarker • Real-world • Real-world evidence • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • CEACAM5 • EGFR