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

NCT04524689 | Terminated Phase 2 Results FDA Drug

• 3 other identifiers: ACT16146U1111-1233-97982023-509115-84
• Study Type: interventional
• Target: 57
• Locations: 8 countries
• Sites: 22

Brief Summary

Primary Objective:

• Safety run-in part: to assess the tolerability and to determine the recommended doses of tusamitamab ravtansine in combination with pembrolizumab and tusamitamab ravtansine in combination with pembrolizumab and platinum-based chemotherapy with or without pemetrexed to be tested in the expansion part of the study in the NSQ NSCLC population
• Expansion part (including participants treated at the recommended dose for expansion \[RDE\] from the Safety Run-in part): to assess the antitumor activity of several dose levels (DLs; if applicable) of tusamitamab ravtansine in combination with pembrolizumab and of several DLs of tusamitamab ravtansine in combination with pembrolizumab, platinum-based chemotherapy, and pemetrexed in the NSQ NSCLC population Secondary Objectives:
• To assess the safety and tolerability of several DLs (if applicable) of tusamitamab ravtansine in combination with pembrolizumab and of 1 DL of tusamitamab ravtansine in combination with pembrolizumab and platinum-based chemotherapy, and of several DLs of tusamitamab ravtansine in combination with pembrolizumab, and platinum-based chemotherapy with pemetrexed in the NSQ NSCLC population
• To assess the antitumor activity of several DLs (if applicable) of tusamitamab ravtansine in combination with pembrolizumab and of 1 DL of tusamitamab ravtansine in combination with pembrolizumab and platinum-based chemotherapy, and of several DLs of tusamitamab ravtansine in combination with pembrolizumab, platinum-based chemotherapy, and pemetrexed in the NSQ NSCLC population
• To assess the durability of the response to treatment with several DLs (if applicable) of tusamitamab ravtansine in combination with pembrolizumab and of 1 DL of tusamitamab ravtansine in combination with pembrolizumab and platinum-based chemotherapy, and of several DLs of tusamitamab ravtansine in combination with pembrolizumab and platinum-based chemotherapy, and pemetrexed in the NSQ NSCLC population
• To assess the antitumor activity of tusamitamab ravtansine in combination with pembrolizumab and platinum-based chemotherapy in the NSQ NSCLC population
• To assess the pharmacokinetics (PK) of tusamitamab ravtansine, pembrolizumab, pemetrexed, cisplatin, and carboplatin, each when given in combination as a doublet (tusamitamab ravtansine + pembrolizumab) or a triplet (tusamitamab ravtansine + pembrolizumab + platinum-based chemotherapy) or a quadruplet (tusamitamab ravtansine + pembrolizumab + platinum-based chemotherapy + pemetrexed)
• To assess the immunogenicity of tusamitamab ravtansine in combination with pembrolizumab and tusamitamab ravtansine in combination with pembrolizumab and platinum based chemotherapy with or without pemetrexed

Conditions

Non-squamous Non-small-cell Lung Cancer (NSQ NSCLC)

Outcome Measures

Primary Outcomes (3)

• All Cohorts: Number of Participants With Study Drug-Related Dose-Limiting Toxicities (DLTs)

  DLTs were defined as: a) Hematological abnormalities: grade 4 neutropenia for 7 or more consecutive days, grade 3 to 4 neutropenia complicated by fever (temperature ≥38.5 degree Celsius on more than 1 occasion) or microbiologically or radiographically documented infection, grade ≥3 thrombocytopenia associated with clinically significant bleeding requiring clinical intervention; b) Non-hematological abnormalities: grade 4 non-hematologic adverse event (AE), except AE symptoms related to the underlying disease as per the Investigator's judgment, grade ≥3 keratopathy. In addition, any other AE that the recruiting Investigators and sponsor deemed to be dose-limiting, regardless of its grade, was also considered as DLT.

  Cycle 1 Day 1 up to Cycle 1 Day 21 (cycle duration=3 weeks)

• Doublet Cohort: Objective Response Rate (ORR)

  ORR was defined as the percentage of participants with a confirmed complete response (CR) or partial response (PR) as best overall response (BOR) per response evaluation criteria in solid tumors (RECIST) version (v) 1.1. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 millimeter (mm). PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

  Tumor assessments performed at baseline, then every 6 weeks for first 24 weeks, and every 9 weeks thereafter, approximately 158.4 weeks

• Quadruplet Cohort: Objective Response Rate

  ORR was defined as the percentage of participants with a confirmed CR or PR as per RECIST v1.1. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

  Tumor assessments performed at baseline, then every 6 weeks for first 24 weeks, and every 9 weeks thereafter, approximately 139.9 weeks

Secondary Outcomes (11)

• All Cohorts: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)

  From first dose of study treatment (Day 1) up to 30 days post last dose of study treatment, approximately 162.4 weeks (doublet), 117 weeks (triplet), and 143.9 weeks (quadruplet)

• Doublet and Quadruplet Cohorts: Progression-free Survival (PFS)

  Tumor assessments performed at baseline, then every 6 weeks for first 24 weeks, and every 9 weeks thereafter, approximately 158.4 weeks (doublet) and 139.9 weeks (quadruplet)

• All Cohorts: Disease Control Rate (DCR)

  Tumor assessments performed at baseline, then every 6 weeks for first 24 weeks, and every 9 weeks thereafter, approximately 158.4 weeks (doublet), 113 weeks (triplet), and 139.9 weeks (quadruplet)

• All Cohorts: Duration of Response (DOR)

  Tumor assessments performed at baseline, then every 6 weeks for first 24 weeks, and every 9 weeks thereafter, approximately 158.4 weeks (doublet), 113 weeks (triplet), and 139.9 weeks (quadruplet)

• Triplet Cohort: Objective Response Rate

  Tumor assessments performed at baseline, then every 6 weeks for first 24 weeks, and every 9 weeks thereafter, approximately 113 weeks

Study Arms (6)

Tusamitamab ravtasine 150 mg/m^2 + Pembrolizumab

EXPERIMENTAL

Pembrolizumab dose will be administered intravenously prior to intravenous administration of tusamitamab ravtansine dose every 3 weeks.

Drug: SAR408701 (Tusamitamab ravtansine); Drug: Pembrolizumab

Tusamitamab ravtasine 170 mg/m^2 + Pembrolizumab

EXPERIMENTAL

Pembrolizumab dose will be administered intravenously prior to intravenous administration of tusamitamab ravtansine dose every 3 weeks.

Drug: SAR408701 (Tusamitamab ravtansine); Drug: Pembrolizumab

Tusamitamab ravtansine 150 mg/m^2 + Pembrolizumab + carboplatin or cisplatin

EXPERIMENTAL

Pembrolizumab dose will be administered intravenously prior to intravenous adminstration of tusamitamab ravtansine dose every 3 weeks. Carboplatin will be infused over 15 to 60 minutes immediately after tusamitamab ravtansine infusion on Day 1 and Q3W for the first 4 cycles. Cisplatin will be infused approximately 30 minutes after tusamitamab ravtansine infusion on Day 1 and Q3W for the first 4 cycles.

Drug: SAR408701 (Tusamitamab ravtansine); Drug: Pembrolizumab; Drug: Cisplatin; Drug: Carboplatin

Tusamitamab ravtansine 170 mg/m^2 + Pembrolizumab + carboplatin or cisplatin

EXPERIMENTAL

Pembrolizumab dose will be administered intravenously prior to intravenous adminstration of tusamitamab ravtansine dose every 3 weeks. Carboplatin will be infused over 15 to 60 minutes immediately after tusamitamab ravtansine infusion on Day 1 and Q3W for the first 4 cycles. Cisplatin will be infused approximately 30 minutes after tusamitamab ravtansine infusion on Day 1 and Q3W for the first 4 cycles.

Drug: SAR408701 (Tusamitamab ravtansine); Drug: Pembrolizumab; Drug: Cisplatin; Drug: Carboplatin

Tusamitamab ravtansine 150 mg/m^2 + Pembrolizumab + carboplatin or cisplatin + pemetrexed

EXPERIMENTAL

Pembrolizumab dose will be administered intravenously prior to intravenous adminstration of tusamitamab ravtansine dose every 3 weeks. Pemetrexed will be infused over 10 minutes after tusamitamab ravtansine infusion on Day 1 and then Q3W. Carboplatin will be infused over 15 to 60 minutes immediately after pemetrexed infusion on Day 1 and Q3W for the first 4 cycles. Cisplatin will be infused approximately 30 minutes after pemetrexed infusion after pemetrexed infusion on Day 1 and Q3W for the first 4 cycles.

Drug: SAR408701 (Tusamitamab ravtansine); Drug: Pembrolizumab; Drug: Cisplatin; Drug: Carboplatin; Drug: Pemetrexed

Tusamitamab ravtansine 170 mg/m^2 + Pembrolizumab + carboplatin or cisplatin + pemetrexed

EXPERIMENTAL

Pembrolizumab dose will be administered intravenously prior to intravenous adminstration of tusamitamab ravtansine dose every 3 weeks. Pemetrexed will be infused over 10 minutes after tusamitamab ravtansine infusion on Day 1 and then Q3W. Carboplatin will be infused over 15 to 60 minutes immediately after pemetrexed infusion on Day 1 and Q3W for the first 4 cycles. Cisplatin will be infused approximately 30 minutes after pemetrexed infusion after pemetrexed infusion on Day 1 and Q3W for the first 4 cycles.

Drug: SAR408701 (Tusamitamab ravtansine); Drug: Pembrolizumab; Drug: Cisplatin; Drug: Carboplatin; Drug: Pemetrexed

Interventions

SAR408701 (Tusamitamab ravtansine) DRUG

Pharmaceutical form:Concentrate for solution for infusion Route of administration: Intravenous

Also known as: Tusamitamab ravtansine

Tusamitamab ravtansine 150 mg/m^2 + Pembrolizumab + carboplatin or cisplatin; Tusamitamab ravtansine 150 mg/m^2 + Pembrolizumab + carboplatin or cisplatin + pemetrexed; Tusamitamab ravtansine 170 mg/m^2 + Pembrolizumab + carboplatin or cisplatin; Tusamitamab ravtansine 170 mg/m^2 + Pembrolizumab + carboplatin or cisplatin + pemetrexed; Tusamitamab ravtasine 150 mg/m^2 + Pembrolizumab; Tusamitamab ravtasine 170 mg/m^2 + Pembrolizumab

Pembrolizumab DRUG

Pharmaceutical form: Concentrate for solution for infusion Route of administration: Intravenous

Also known as: Keytruda

Tusamitamab ravtansine 150 mg/m^2 + Pembrolizumab + carboplatin or cisplatin; Tusamitamab ravtansine 150 mg/m^2 + Pembrolizumab + carboplatin or cisplatin + pemetrexed; Tusamitamab ravtansine 170 mg/m^2 + Pembrolizumab + carboplatin or cisplatin; Tusamitamab ravtansine 170 mg/m^2 + Pembrolizumab + carboplatin or cisplatin + pemetrexed; Tusamitamab ravtasine 150 mg/m^2 + Pembrolizumab; Tusamitamab ravtasine 170 mg/m^2 + Pembrolizumab

Cisplatin DRUG

Pharmaceutical form: Lyophilized powder for reconstitution in solution Route of administration: Intravenous

Tusamitamab ravtansine 150 mg/m^2 + Pembrolizumab + carboplatin or cisplatin; Tusamitamab ravtansine 150 mg/m^2 + Pembrolizumab + carboplatin or cisplatin + pemetrexed; Tusamitamab ravtansine 170 mg/m^2 + Pembrolizumab + carboplatin or cisplatin; Tusamitamab ravtansine 170 mg/m^2 + Pembrolizumab + carboplatin or cisplatin + pemetrexed

Carboplatin DRUG

Pharmaceutical form: Concentrate for solution for infusion Route of administration: Intravenous

Tusamitamab ravtansine 150 mg/m^2 + Pembrolizumab + carboplatin or cisplatin; Tusamitamab ravtansine 150 mg/m^2 + Pembrolizumab + carboplatin or cisplatin + pemetrexed; Tusamitamab ravtansine 170 mg/m^2 + Pembrolizumab + carboplatin or cisplatin; Tusamitamab ravtansine 170 mg/m^2 + Pembrolizumab + carboplatin or cisplatin + pemetrexed

Pemetrexed DRUG

Pharmaceutical form: Concentrate for solution for infusion Route of administration: Intravenous

Tusamitamab ravtansine 150 mg/m^2 + Pembrolizumab + carboplatin or cisplatin + pemetrexed; Tusamitamab ravtansine 170 mg/m^2 + Pembrolizumab + carboplatin or cisplatin + pemetrexed

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically- or cytologically-confirmed diagnosis of advanced or metastatic NSQ NSCLC with no EGFR sensitizing mutation or BRAF mutation or ALK/ROS alterations.
• No prior systemic chemotherapy for the treatment of the participant's advanced or metastatic disease (treatment with chemotherapy and/or radiation as part of neoadjuvant/adjuvant therapy is allowed as long as completed at least 6 months prior to diagnosis of advanced or metastatic disease).
• Expression of CEACAM5 as demonstrated prospectively by a centrally assessed Immunohistochemistry (IHC) assay of ≥2+ in intensity involving at least 1% of the tumor cell population in archival tumor sample (or if not available fresh biopsy sample).
• Measurable disease based on RECIST 1.1.
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1
• Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies
• Life expectancy of at least 3 months

You may not qualify if:

• Medical condition requiring concomitant administration of a medication with a strong CYP3A inhibitor.
• Uncontrolled brain metastases and history of leptomeningeal disease.
• Significant concomitant illness, including any severe medical condition that, in the opinion of the investigator or Sponsor, would impair the patient's participation in the study or interpretation of the results.
• History within the last 3 years of an invasive malignancy other than the one treated in this study, with the exception of resected/ablated basal or squamous-cell carcinoma of the skin or carcinoma in situ of the cervix, or other local tumors considered cured by local treatment.
• History of known acquired immunodeficiency syndrome (AIDS) related illnesses or known HIV disease requiring antiretroviral treatment, or active hepatitis A, B, or C infection.
• History of active autoimmune disease that has required systemic treatment in the past 2 years.
• History of allogeneic tissue/solid organ transplantation.
• Active infection requiring IV systemic therapy within 2 weeks prior to randomization or active tuberculosis.
• Interstitial lung disease or history of pneumonitis that has required oral or IV steroids
• Non-resolution of any prior treatment-related toxicity to \< Grade 2 according to NCI CTCAE V5.0, with the exception of alopecia, vitiligo, or active thyroiditis controlled with hormone replacement therapy.
• Unresolved corneal disorder or any previous corneal disorder considered by an ophthalmologist to predict higher risk of drug-induced keratopathy. The use of contact lenses is not permitted.
• Symptomatic herpes zoster within 3 months prior to screening.
• Significant allergies to humanized monoclonal antibodies.
• Clinically significant multiple or severe drug allergies, intolerance to topical corticosteroids, or severe post-treatment hypersensitivity reactions (including, but not limited to, erythema multiforme major, linear immunoglobulin A \[IgA\] dermatosis, toxic epidermal necrolysis, and exfoliative dermatitis).
• Concurrent treatment with any other anticancer therapy.

Sponsors & Collaborators

• Sanofi: lead

Study Sites (22)

KU Medical Center_Investigational Site Number :8400002

Westwood, Kansas, 66205, United States

Location

Centro Avancado de Oncologia CECAN - Liga Contra o Cancer Site Number : 0760004

Natal, Rio Grande do Norte, 59062-000, Brazil

Location

Centro de Investigacion y Desarrollo Oncologico (CIDO) Hochstetter 599 of. 602-603-1001, Temuco_Investigational Site Number :1520005

Temuco, La Araucanía, 4780000, Chile

Location

ONCOCENTRO APYS Av. La Marina 1702, 2do piso, Viña del Mar_Investigational Site Number :1520003

Viña del Mar, Región de Valparaíso, 2520598, Chile

Location

Orlandi Oncologia General Salvo 159, Providencia_Investigational Site Number :1520002

Santiago, 7500713, Chile

Location

ICEGCLINIC Avenida Serafín Zamora 190 Torre B, piso 4. La Florida_Investigational Site Number :1520006

Santiago, 8241470, Chile

Location

Fakultní nemocnice Olomouc Onkologická klinika I.P. Pavlova 6_Site Number :2030001

Olomouc, 77900, Czechia

Location

Nemocnice AGEL Ostrava - Vitkovice Plicní oddělení Zalužanského 2214/35_Site Number :2030002

Ostrava - Vitkovice, 70384, Czechia

Location

Institut Sainte-Catherine 250 Chemin de Baigne-Pieds_Investigational Site Number :2500005

Avignon, 84918, France

Location

CHRU BREST 5 Avenue Foch_Investigational Site Number :2500003

Brest, 29200, France

Location

Centre François Magendie Hôpital du Haut Lévèque Av.de Magellan_Investigational Site Number :2500001

Pessac, 33600, France

Location

Pôle régional de Cancérologie 2 rue de la Milèterie BP 577_Investigational Site Number :2500004

Poitiers, 86021, France

Location

Országos Onkológiai Intézet Ráth György u. 7_Investigational Site Number :3480002

Budapest, 1122, Hungary

Location

Veszprém Megyei Tüdőgyógyintézet 049/2 Hrsz_Investigational Site Number :3480004

Farkasgyepü, 8582, Hungary

Location

Investigational Site Number : 3760001

Ramat Gan, 5266202, Israel

Location

Investigational Site Number : 3760002

Tel Aviv, 64239, Israel

Location

Investigational Site Number : 7240005

A Coruña, A Coruña [La Coruña], 15006, Spain

Location

Investigational Site Number : 7240006

Badalona, Catalunya [Cataluña], 08916, Spain

Location

Investigational Site Number : 7240007

Oviedo, Principality of Asturias, 33011, Spain

Location

Investigational Site Number : 7240002

Las Palmas, 35016, Spain

Location

Investigational Site Number : 7240004

Madrid, 28040, Spain

Location

Investigational Site Number : 7240001

Madrid, 28041, Spain

Location

Related Links

• ACT16146 Plain Language Results Summary

MeSH Terms

Interventions

tusamitamab ravtansine; pembrolizumab; Cisplatin; Carboplatin; Pemetrexed

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Coordination Complexes; Organic Chemicals; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic

Limitations and Caveats

The study was terminated due to the discontinuation of the overall development of tusamitamab ravtansine by the Sponsor and the enrollment of new participants in this study had been stopped on 21 December 2023.

Results Point of Contact

• Title: Trial Transparency Team
• Organization: Sanofi aventis recherche & développement

Contact-US@sanofi.com

800-633-1610

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 20, 2020
• First Posted: August 24, 2020
• Study Start: October 26, 2020
• Primary Completion: March 12, 2024
• Study Completion: December 24, 2024
• Last Updated: October 29, 2025
• Results First Posted: March 17, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share

Locations

US (1); BR (1); ES (6); IL (2); CL (4); CZ (2); FR (4); HU (2)