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

NCT ID: NCT04524689

Last Updated: 2025-10-29

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 57 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-10-26
• Study Completion Date: 2024-12-24

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

Detailed Description

The expected duration of study intervention for participants may vary, based on disease progression date; median expected duration of study per participant is estimated at 10 months (up to 1 month for screening, a median of 6 months for treatment, a median of 1 month for EOT, and follow-up visit 90 days after the last IMP administration).

Conditions

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

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Tusamitamab ravtasine 150 mg/m^2 + Pembrolizumab

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

Group Type: EXPERIMENTAL

SAR408701 (Tusamitamab ravtansine)

Intervention Type: DRUG

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

Pembrolizumab

Intervention Type: DRUG

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

Tusamitamab ravtasine 170 mg/m^2 + Pembrolizumab

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

Group Type: EXPERIMENTAL

SAR408701 (Tusamitamab ravtansine)

Intervention Type: DRUG

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

Pembrolizumab

Intervention Type: DRUG

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

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

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.

Group Type: EXPERIMENTAL

SAR408701 (Tusamitamab ravtansine)

Intervention Type: DRUG

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

Pembrolizumab

Intervention Type: DRUG

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

Cisplatin

Intervention Type: DRUG

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

Carboplatin

Intervention Type: DRUG

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

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

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.

Group Type: EXPERIMENTAL

SAR408701 (Tusamitamab ravtansine)

Intervention Type: DRUG

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

Pembrolizumab

Intervention Type: DRUG

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

Cisplatin

Intervention Type: DRUG

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

Carboplatin

Intervention Type: DRUG

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

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

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.

Group Type: EXPERIMENTAL

SAR408701 (Tusamitamab ravtansine)

Intervention Type: DRUG

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

Pembrolizumab

Intervention Type: DRUG

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

Cisplatin

Intervention Type: DRUG

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

Carboplatin

Intervention Type: DRUG

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

Pemetrexed

Intervention Type: DRUG

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

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

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.

Group Type: EXPERIMENTAL

SAR408701 (Tusamitamab ravtansine)

Intervention Type: DRUG

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

Pembrolizumab

Intervention Type: DRUG

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

Cisplatin

Intervention Type: DRUG

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

Carboplatin

Intervention Type: DRUG

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

Pemetrexed

Intervention Type: DRUG

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

Interventions

SAR408701 (Tusamitamab ravtansine)

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

Intervention Type: DRUG

Pembrolizumab

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

Intervention Type: DRUG

Cisplatin

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

Intervention Type: DRUG

Carboplatin

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

Intervention Type: DRUG

Pemetrexed

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

Intervention Type: DRUG

Other Intervention Names

Tusamitamab ravtansine; Keytruda

Eligibility Criteria

Inclusion Criteria

• 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

Exclusion Criteria

• 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.
• Have received prior chemotherapy treatment for advanced/metastatic NSCLC.
• The patient is a candidate for a curative treatment with either surgical resection and/or chemoradiation
• Washout period before the first administration of study intervention of less than 3 weeks or less than 5 times the half-life, whichever is shorter, for any investigational treatment).
• Any prior therapy targeting CEACAM5.
• Any prior treatment with any other anti-PD-1, or PD-L1 or programmed death ligand 2 (PD-L2), anti-CD137, or anti-cytotoxic T-lymphocyte-associated antigen-4.
• Any prior maytansinoid treatment (DM1 or DM4 ADC).
• Is receiving systemic steroid therapy ≤3 days prior to the first dose of study therapy or receiving any other form of immunosuppressive medication. Daily steroid replacement therapy or any corticosteroid premedication if applicable are allowed.
• Any radiation therapy to lung >30 Gy within 6 months of first study intervention administration.
• Has received or will receive a live vaccine within 30 days prior to the first study intervention administration.
• Any major surgery within the preceding 3 weeks of the first study intervention administration.

Prior/concurrent clinical study experience

• Current participation in any other clinical study involving an investigational study treatment or any other type of medical research.
• Poor organ function

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sanofi

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Sciences & Operations

Role: STUDY_DIRECTOR

Sanofi

Locations

KU Medical Center_Investigational Site Number :8400002

Westwood, Kansas, United States

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

Natal, Rio Grande do Norte, Brazil

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

Temuco, La Araucanía, Chile

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

Viña del Mar, Región de Valparaíso, Chile

Orlandi Oncologia General Salvo 159, Providencia_Investigational Site Number :1520002

Santiago, , Chile

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

Santiago, , Chile

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

Olomouc, , Czechia

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

Ostrava - Vitkovice, , Czechia

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

Avignon, , France

CHRU BREST 5 Avenue Foch_Investigational Site Number :2500003

Brest, , France

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

Pessac, , France

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

Poitiers, , France

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

Budapest, , Hungary

Veszprém Megyei Tüdőgyógyintézet 049/2 Hrsz_Investigational Site Number :3480004

Farkasgyepü, , Hungary

Investigational Site Number : 3760001

Ramat Gan, , Israel

Investigational Site Number : 3760002

Tel Aviv, , Israel

Investigational Site Number : 7240005

A Coruña, A Coruña [La Coruña], Spain

Investigational Site Number : 7240006

Badalona, Catalunya [Cataluña], Spain

Investigational Site Number : 7240007

Oviedo, Principality of Asturias, Spain

Investigational Site Number : 7240002

Las Palmas, , Spain

Investigational Site Number : 7240004

Madrid, , Spain

Investigational Site Number : 7240001

Madrid, , Spain

Countries

United States; Brazil; Chile; Czechia; France; Hungary; Israel; Spain

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

https://sanofi.trialsummaries.com/Study/StudyDetails?id=25189&tenant=MT_SNY_9011

ACT16146 Plain Language Results Summary

Other Identifiers

U1111-1233-9798

Identifier Type: REGISTRY

Identifier Source: secondary_id

2023-509115-84

Identifier Type: REGISTRY

Identifier Source: secondary_id

ACT16146

Identifier Type: -

Identifier Source: org_study_id