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Dose escalation administered intravenously, once every two weeks

Administered intravenously at the maximum tolerated dose (MTD), once every 2 weeks, to patients with colorectal cancer

Administered intravenously at the MTD, once every 2 weeks, to patients with carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) expressing non-squamous non-small cell lung cancer (NSCLC) of at least 50% of tumor cells at or above 2+ intensity

Administered intravenously at the MTD, once every 2 weeks, to patients with CEACAM5 expressing gastric adenocarcinoma

Loading dose escalation administered intravenously at first cycle, followed by MTD, once every 2 weeks

Administered intravenously at the MTD, once every 2 weeks, to patients with CEACAM5 expressing non-squamous NSCLC of at least 1% but below 50% of tumor cells at or above 2+ intensity

Loading dose of determined MTD-L administered intravenously at first cycle, followed by MTD, once every 2 weeks

Administered intravenously at the MTD, once every 2 weeks, to patients with CEACAM5 expressing SCLC

Dose escalation administered intravenously, once every three weeks

Pharmaceutical form: concentrate for solution for infusion Route of administration: intravenous

SAR408701

Clinical Sciences & Operations

Primary Objectives:

* To determine the maximum tolerated dose (MTD) of SAR408701 administered as monotherapy, once every 2 weeks (with and without a loading dose at Cycle 1) to patients with advanced solid tumors (Main Escalation and Loading Dose Escalation Q2W).
* To determine the maximum tolerated dose (MTD) of SAR408701 administered as monotherapy, once every 3 weeks to patients with advanced solid tumors (Escalation Q3W Cycle).
* To assess efficacy according to Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1) (Expansion Phase) when SAR408701 is administered once every 2 weeks with or without a loading dose at Cycle 1.

Secondary Objectives:

* To characterize the overall safety profile of SAR408701.
* To characterize the pharmacokinetic (PK) profile of SAR408701 and of its potential circulating derivatives.
* To identify the recommended phase 2 dose (RP2D) of SAR408701.
* To assess the potential immunogenicity of SAR408701.

The study duration for an individual patient will start from the signature of the informed consent, will include a period to assess eligibility (screening period) of up to approximately 4 weeks (28 days), a treatment period and an end-of-treatment visit around 30 days following the last administration of study drug, and at least one follow-up visit after the end-of-treatment visit. Additional follow-up visits may be required until resolution or stabilization of adverse events (at least 30 days). Treatment may continue until precluded by toxicity, progression, or upon patient's request. If the patient stops study treatment for reason other than disease progression, follow-up visit will be performed every 3 months until disease progression or initiation of another anti-tumor treatment or death, whichever comes first.

Evaluation of SAR408701 in Patients With Advanced Solid Tumors

A First-in-Human Study for the Evaluation of the Safety, Pharmacokinetics and Antitumor Activity of SAR408701 in Patients With Advanced Solid Tumors

Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org

Sanofi

Anti-Inflammatory Agents

Antineoplastic Agents

Antiemetics

Gastrointestinal Agents

Anti-Allergic Agents

Central Nervous System Depressants

Dermatologic Agents

Vasoconstrictor Agents

Respiratory System Agents

Central Nervous System Stimulants

Dexamethasone

Ophthalmic Solutions

Dexamethasone acetate

Diphenhydramine

Promethazine

Naphazoline

Glucocorticoids

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

Hypnotics and Sedatives

Anesthetics

Anesthetics, Local

Histamine H1 Antagonists

Histamine

Histamine phosphate

Histamine Antagonists

Neurotransmitter Agents

Adrenergic Agents

Adrenergic alpha-Agonists

Adrenergic Agonists

Ephedrine

Pseudoephedrine

Nasal Decongestants

SAR408701 Dose escalation administered as a single agent intravenously, on Day 1 and once every two weeks, to patients with malignant solid tumors

Pharmaceutical form: solution for infusion

Route of administration: intravenous

Pharmaceutical form: solution for eye drop

Route of administration: eye drop

dexamethasone

naphazoline

Pharmaceutical form: tablet

Route of administration: oral

diphenhydramine

Primary Objective:

* To evaluate tolerability and safety of SAR408701 when administered as a single agent according to the investigational medicinal product (IMP) related dose limiting toxicities (DLTs) to determine the recommended dose (RD) of SAR408701 in Japanese patients with advanced malignant solid tumors.

Secondary Objectives:

* To characterize the overall safety profile of SAR408701 monotherapy.
* To characterize the pharmacokinetic (PK) profile of SAR408701 and its metabolites.
* To evaluate the pharmacodynamic (PDy) effect of SAR408701 on levels of circulating carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) for main dose escalation part.
* To assess preliminary efficacy according to Response Evaluation Criteria in Solid Tumor (RECIST) 1.1 criteria and other indicators of antitumor activity.
* To assess the potential immunogenicity of SAR408701.

The study duration per participant will include a period to assess eligibility (screening period) of up to approximately 4 weeks (28 days), a treatment period and an End-of-Treatment (EOT) visit around 30 days after the last administration of IMP, and at least one follow-up (FU) visit after the EOT visit.

Evaluation of SAR408701 in Japanese Patients With Advanced Malignant Solid Tumors

A Phase I Study to Evaluate Safety and Pharmacokinetics of SAR408701 Administered Intravenously as Monotherapy in Japanese Patients With Advanced Malignant Solid Tumors

IMP-related DLTs are defined as adverse events (AE) related to the IMPs in absence of clear evidence to the contrary, after validation by the Study Committee, and if not related to a disease progression, graded using National Cancer Institute common Toxicity Criteria (NCI-CTC) scale v4.03

Overall safety profile characterized in terms of the type, frequency, severity, seriousness, and relationship to study therapy of any AEs based on standard and systematic assessment including physical findings, laboratory tests or other investigations

Cmax for SAR408701 will be assessed after single and repeat doses, as relevant

Cmax for DM4 and Me-DM4 will be assessed after single and repeat doses, as relevant

Tmax for SAR408701 will be assessed after single and repeat doses, as relevant

Tmax for DM4 and Me-DM4 will be assessed after single and repeat doses, as relevant

AUC of SAR408701 from time zero extrapolated to infinity

AUC of DM4 and Me-DM4 from time zero extrapolated to infinity

Assessment of plasma CEACAM5 levels in main dose-escalation part

Assessment of tumor response using standard imaging, as defined by RECIST 1.1 criteria

Immunogenicity evaluation for anti-SAR408701 antibodies

Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Carcinoma

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Pembrolizumab

Immune Checkpoint Inhibitors

Ramucirumab

Antineoplastic Agents, Immunological

Angiogenesis Inhibitors

Growth Inhibitors

Ramucirumab will be administered intravenously prior to intravenously adminstration of SAR408701 every two 2 weeks.

Participants will be treated with tusamitamab ravtansine and ramucirumab and pembrolizumab to assess the tolerability of the combination

Pharmaceutical form:concentrate for solution for injection Route of administration: intravenous infusion

Pharmaceutical form: concentrate for solution for injection Route of administration: intravenous infusion

ramucirumab

pembrolizumab

Primary Objectives:

Doublet Cohort

Part 1 (safety run-in):

To assess the tolerability and to confirm the recommended dose of tusamitamab ravtansine in combination with ramucirumab in the NSQ NSCLC population.

Part 2:

To assess the antitumor activity of tusamitamab ravtansine in combination with ramucirumab in the NSQ NSCLC population.

Triplet cohort

To assess the tolerability and to confirm the recommended dose of tusamitamab ravtansine in combination with ramucirumab and pembrolizumab in the NSQ NSCLC population.

Secondary Objectives:

Doublet Cohort

To assess the safety and tolerability of tusamitamab ravtansine in combination with ramucirumab.

To assess the durability of the response to treatment with tusamitamab ravtansine in combination with ramucirumab.

To assess anti-tumor activity of tusamitamab ravtansine in combination with ramucirumab on progression free survival (PFS) and disease control rate (DCR).

To assess the pharmacokinetic (PK) profiles of tusamitamab ravtansine (SAR408701) and ramucirumab when given in combination.

To assess the immunogenicity of tusamitamab ravtansine (SAR408701) when given in combination with ramucirumab.

Triplet cohort

To assess the safety and tolerability of tusamitamab ravtansine in combination with ramucirumab and pembrolizumab

To assess the antitumor activity of tusamitamab ravtansine in combination with ramucirumab and pembrolizumab in the NSQ NSCLC population.

To assess the immunogenicity of tusamitamab ravtansine when given in combination with ramucirumab and pembrolizumab

The expected duration of the study intervention for participants may vary, based on progression date ; median expected duration of study per participant is estimated 11 months (up to 1 month for screening, a median of 6 months for treatment, and a median of 4 months for end-of-treatment assessments and safety follow-up visit)

Tusamitamab Ravtansine (SAR408701) in Combination With Ramucirumab or Ramucirumab and Pembrolizumab in Pretreated Patients With NSQ NSCLC (CARMEN-LC04)

Open-label, Single-arm Trial to Evaluate Antitumor Activity, Safety, and Pharmacokinetics of Tusamitamab Ravtansine (SAR408701) Used in Combination With Ramucirumab or Ramucirumab and Pembrolizumab in Metastatic, Non-squamous, Non Small-cell Lung Cancer (NSQ NSCLC) Patients With CEACAM5-positive Tumors, Previously Treated With Platinum-based Chemotherapy and an Immune Checkpoint Inhibitor

The following AEs occurred during the first 2 cycles of treatment, unless due to disease progression or to a cause obviously unrelated to study drug, were considered DLTs:

* Grade 4 neutropenia for 7 or more consecutive days.
* Grade 3 to 4 neutropenia complicated by fever.
* Grade \>=3 thrombocytopenia.
* Elevated urine protein \>=3 gram(g)/24 hour.
* Grade 4 non-hematologic AE.
* Grade \>=3 keratopathy.
* Grade 4 or refractory hypertension. In addition, any other AE that the Investigators and sponsor deemed to be dose limiting, regardless of its grade, was also considered as DLT.

The ORR is defined as percentage of participants with confirmed complete response (CR) or partial response (PR) as best overall response (BOR) determined per Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1. The CR is defined as disappearance of all target lesions. The PR is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

The following AEs occurred during the first cycle of treatment, unless due to disease progression or to a cause obviously unrelated to study drug, were considered DLTs:

* Grade 4 neutropenia for 7 or more consecutive days.
* Grade 3 to 4 neutropenia complicated by fever.
* Grade \>=3 thrombocytopenia.
* Elevated urine protein \>=3 g/24 hour.
* Grade 4 non-hematologic AE.
* Grade \>=3 keratopathy.
* Grade 4 or refractory hypertension. In addition, any other AE that the Investigators and sponsor deemed dose limiting, regardless of its grade, was also considered as DLT.

An AE is any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study drug, whether or not considered related to the study drug. A SAE is defined as any untoward medical occurrence that, at any dose: results in death or life-threatening or requires inpatient hospitalization or prolongation of existing hospitalization or results in persistent disability/incapacity or congenital anomaly/birth defect. TEAE is defined as AEs that develop, worsen, or become serious during the treatment period.

Blood samples were collected to determine the clinical chemistry laboratory abnormalities.

A single 12-lead ECG was recorded using an ECG machine that automatically calculates the heart rate and measures PR, QRS, and QT intervals.

Urine samples were collected to determine the clinical chemistry laboratory abnormalities.

The DOR is defined as the time from first documented evidence of CR or PR until progressive disease (PD) determined per RECIST v1.1 or death from any cause, whichever occurs first. The PD is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study.

The PFS is defined as the time from the first study drug administration to the date of the first documented disease progression or death due to any cause, whichever comes first.

The DCR is defined as the percentage of participants who achieved confirmed CR, confirmed PR or stable disease (SD) as per RECIST v1.1. The SD is defined as neither sufficient shrinkage from the baseline study to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.

The ORR is defined as percentage of participants with confirmed CR or PR as BOR determined per RECIST v1.1.

Blood samples were collected for the measurement of Cmax of tusamitamab ravtansine and ramucirumab concentrations. Cmax of tusamitamab ravtansine will be calculated using non-compartmental method.

Blood samples were collected for the measurement of AUC0-14d of tusamitamab ravtansine and ramucirumab concentrations. AUC0-14d will be calculated using the trapezoidal method from time 0 to 14 days and non-compartmental method.

Blood samples were collected for the measurement of Ctrough of tusamitamab ravtansine and ramucirumab concentrations. Ctrough of tusamitamab ravtansine was calculated using non-compartmental method.

Blood samples were collected to assess the presence of ATA against tusamitamab ravtansine in plasma from all participants.

Analysis was performed on all-treated population.

Participants received tusamitamab ravtansine 100 mg/m\^2 and ramucirumab 8 mg/kg IV infusion Q2W until disease progression, unacceptable AE, or the participant's or investigator's decision to stop the treatment.

Tusamitamab Ravtansine 100 mg/m^2 + Ramucirumab

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

All-treated population included all enrolled participants exposed to the study treatment, regardless of the amount of treatment administered.

Trial Transparency Team

DLT-evaluable (Part 1) population included all enrolled participants who received 2 cycles with at least 80% of the intended dose for both tusamitamab ravtansine and ramucirumab at each of the 2 first infusions unless they discontinued the study intervention before the end of Cycle 2 due to a DLT.

Doublet Cohort - Part 1: Number of Participants With Study Drug-Related Dose-Limiting Toxicity (DLT)

Doublet Cohort - Part 2: Objective Response Rate (ORR)

Participants were planned to receive tusamitamab ravtansine 150 mg/m\^2 plus ramucirumab 10 mg/kg and pembrolizumab 200 mg IV infusion every 3 weeks (Q3W) until disease progression, unacceptable AE, or the participant's or investigator's decision to stop the treatment.

Tusamitamab Ravtansine 100 mg/m^2 + Ramucirumab + Pembrolizumab

Data not collected because triplet cohort was not initiated.

Triplet Cohort: Number of Participants With Study Drug-Related Dose-Limiting Toxicity

Doublet and Triplet Cohorts: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

Doublet and Triplet Cohorts: Number of Participants With Potentially Clinically Significant Abnormalities in Clinical Laboratory Parameters

Doublet and Triplet Cohorts: Number of Participants With Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG)

Doublet and Triplet Cohorts: Number of Participants With Potentially Clinically Significant Abnormalities in Urinalysis

Doublet Cohort: Duration of Response (DOR)

Doublet Cohort: Progression-Free Survival (PFS)

Doublet Cohort: Disease Control Rate (DCR)

Triplet Cohort: Objective Response Rate

Doublet Cohort: Maximum Observed Concentration (Cmax) of Tusamitamab Ravtansine and Ramucirumab

Doublet Cohort: Area Under the Plasma Concentration Versus Time Curve From Time 0 to 14 Days (AUC0-14d) of Tusamitamab Ravtansine and Ramucirumab

Doublet Cohort: Concentration Observed Before Treatment Administration During Repeated Dosing (Ctrough) of Tusamitamab Ravtansine and Ramucirumab

Doublet and Triplet Cohorts: Number of Participants With Anti-Therapeutic Antibodies (ATAs) Against Tusamitamab Ravtansine

Participants received tusamitamab ravtansine 100 milligram per square meter (mg/m\^2) and ramucirumab 8 mg per kilogram (kg) intravenous (IV) infusion every 2 weeks (Q2W) until disease progression, unacceptable adverse event (AE), or the participant's or investigator's decision to stop the treatment.

Overall Study

Symptoms and General Pathology

Tissue Adhesions

Docetaxel

Tubulin Modulators

Antimitotic Agents

Administered intravenously once every 2 weeks

Administered intravenously once every 3 weeks

Pharmaceutical form: Concentrate for solution for intravenous infusion Route of administration: intravenous (IV) infusion

Pharmaceutical form: Concentrate for solution for intravenous infusion Route of administration: IV infusion

Primary Objectives:

* Study is designed with two primary endpoints that will be analyzed on randomized participants at the time of the cut-off date for each given analysis (progression free survival \[PFS\] and overall survival \[OS\])
* Study success is defined either on PFS or OS
* The primary objective is to determine whether tusamitamab ravtansine improves the progression free survival (PFS) when compared to docetaxel in participants with metastatic non-squamous non-small-cell lung cancer (NSCLC) expressing CEACAM5 greater than or equal to 2+ in intensity in at least 50% of the tumor cell population and previously treated with standard-of-care platinum-based chemotherapy and an immune checkpoint inhibitor (ICI)
* The primary objective is to determine whether tusamitamab ravtansine improves the overall survival (OS) when compared with docetaxel in participants with metastatic non-squamous NSCLC expressing CEACAM5 greater than or equal to 2+ in intensity in at least 50% of the tumor cell population and previously treated with standard-of-care platinum-based chemotherapy and an immune checkpoint inhibitor.

Secondary Objectives:

* To compare the objective response rate (ORR) of tusamitamab ravtansine with docetaxel
* To compare the health-related quality of life (HRQOL) of tusamitamab ravtansine with docetaxel
* To evaluate the safety of tusamitamab ravtansine compared to docetaxel
* To assess the duration of response (DOR) of tusamitamab ravtansine as compared with docetaxel

The expected duration of study intervention for participants who benefit from study intervention may vary, based on progression date; but median expected duration of study per participant is estimated as median 9 months in docetaxel arm (1 month for screening, 4 months for treatment, and 4 months for the EOT and follow-up visits) and 12.5 months in SAR408701 arm (1 month for screening, 6.5 months for treatment, and 5 months for end of treatment follow-up).

SAR408701 Versus Docetaxel in Previously Treated, Carcinoembryonic Antigen-related Cell Adhesion Molecule 5 (CEACAM5) Positive Metastatic Non-squamous Non-small-cell Lung Cancer Patients

Randomized, Open-label, Phase 3 Study of SAR408701 Versus Docetaxel in Previously Treated, Metastatic Nonsquamous, Non-small-cell Lung Cancer Patients With CEACAM5-positive Tumors

PFS will be defined as the time from randomization to the date of the first documented disease progression or death of any cause, whichever comes first.

OS will be defined as the time of randomization to the date of death due to any cause.

Objective response rate will be defined as the proportion of participants who have a complete response (CR) or partial response (PR), as best overall response derived from Overall Response (OR) determined by the Independent Radiology Review Committee (IRC) per Response Evaluation Criteria in Solid Tumor (RECIST) 1.1

Time to deterioration (TTD) in disease related symptoms as determined by European Organization for Research and Treatment for Cancer (EORTC)- Quality of life Questionnaire (QLQ)-Lung Cancer (LC)13

TTD in physical function as determined by EORTC QLQ C30

TTD in role function as determined by EORTC QLQ C30

Incidence of TEAEs and SAEs and laboratory abnormalities according to NCI CTCAE V5

Duration of response (DOR) is defined as the time from first documented evidence of complete response (CR) or partial response (PR) until progressive disease (PD) determined per RECIST 1.1 or death from any cause, whichever occurs first.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Evaluation of SAR408701 in Patients With Advanced Solid Tumors	NCT02187848	Neoplasm Malign...	SAR408701	18 Years -	Sanofi
Evaluation of SAR408701 in Japanese Patients With Advanced Malignant Solid Tumors	NCT03324113	Neoplasm Malign...	SAR408701 dexamethasone naphazoline diphenhydramine	20 Years -	Sanofi
Tusamitamab Ravtansine (SAR408701) in Combination With Ramucirumab or Ramucirumab and Pembrolizumab in Pretreated Patients With NSQ NSCLC (CARMEN-LC04)	NCT04394624	Non-small Cell ...	SAR408701 ramucirumab pembrolizumab	18 Years -	Sanofi
Evaluation of SAR408701 in Japanese Patients With Advanced Malignant Solid Tumors	NCT03324113	Neoplasm Malign...	SAR408701 dexamethasone naphazoline diphenhydramine	20 Years -	Sanofi
SAR408701 Versus Docetaxel in Previously Treated, Carcinoembryonic Antigen-related Cell Adhesion Molecule 5 (CEACAM5) Positive Metastatic Non-squamous Non-small-cell Lung Cancer Patients	NCT04154956	Non-small Cell ...	SAR408701 Docetaxel	18 Years -	Sanofi

Spots Global Cancer Trial Database for sar408701

Every month we try and update this database with for sar408701 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for sar408701

Every month we try and update this database with for sar408701 cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for sar408701 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.