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

Evaluation of tusamitamab ravtansine, a CEACAM5-targeting antibody drug conjugate, in nonsquamous NSCLC participants with negative or moderate CEACAM5 expression and high circulating CEA: results from phase 2 CARMEN-LC06 trial (ELCC 2025) - No abstract available

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

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: May 2024 ➔ Sep 2024

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

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: Apr 2024 ➔ Aug 2024

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

Tusamitamab Ravtansine (SAR408701) in Combination With Ramucirumab or Ramucirumab and Pembrolizumab in Pretreated Patients With NSQ NSCLC (CARMEN-LC04) (clinicaltrials.gov) - P2 | N=31 | Active, not recruiting | Sponsor: Sanofi | Trial completion date: Mar 2024 ➔ Sep 2024

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

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