Trial Outcomes & Findings for SAR408701 Versus Docetaxel in Previously Treated, Carcinoembryonic Antigen-related Cell Adhesion Molecule 5 (CEACAM5) Positive Metastatic Non-squamous Non-small-cell Lung Cancer Patients (NCT NCT04154956)

Last Updated: 2025-08-05

Results Overview

PFS was defined as the time from the date of randomization to the date of the first documentation of objective PD as assessed by radiological review committee (IRC) according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) definitions or death due to any cause before the study cut-off date, whichever occurred first. PD was defined as unequivocal progression of existing non-target lesions; appearance of 1 or more new lesions; at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 millimeters (mm).

Recruitment status

ACTIVE_NOT_RECRUITING

Study phase

PHASE3

Target enrollment

389 participants

Primary outcome timeframe

Tumor assessments performed at screening, and every 8 weeks +/-5 days thereafter, up to 189 weeks

Results posted on

2025-08-05

Participant Flow

The study was conducted at 161 centers in 25 countries from 06 February 2020 to 22 September 2023 (primary completion date). Results are reported as per the primary completion date of 22 September 2023.

A total of 490 participants were screened, of which 389 participants were randomized in a ratio of 1:1 to either tusamitamab ravtansine or docetaxel arm. The randomization was stratified by Eastern Cooperative Oncology Group (ECOG) performance status (0 versus 1), previous immune checkpoint inhibitor treatment (sequential versus combination with chemotherapy) and geographical region (Asia versus Western Europe + Australia + North America versus Rest of the World \[RoW\]).

Participant milestones

Participant milestones
Measure	Tusamitamab Ravtansine Participants received tusamitamab ravtansine 100 milligrams per square meter (mg/m\^2) by intravenous (IV) infusion, once every 2 weeks (Q2W) until objective progressive disease (PD), unacceptable adverse event/toxicity, upon participant's request to stop treatment, or Investigator decision, whichever occurred first (maximum exposure: 147 weeks).	Docetaxel Participants received docetaxel 75 mg/m\^2 by IV infusion, once every 3 weeks (Q3W) until objective PD, unacceptable adverse event/toxicity, upon participant's request to stop treatment, or Investigator decision, whichever occurred first (maximum exposure: 115 weeks).
Overall Study STARTED	194	195
Overall Study Randomized and Treated	194	177
Overall Study COMPLETED	48	52
Overall Study NOT COMPLETED	146	143

Reasons for withdrawal

Reasons for withdrawal
Measure	Tusamitamab Ravtansine Participants received tusamitamab ravtansine 100 milligrams per square meter (mg/m\^2) by intravenous (IV) infusion, once every 2 weeks (Q2W) until objective progressive disease (PD), unacceptable adverse event/toxicity, upon participant's request to stop treatment, or Investigator decision, whichever occurred first (maximum exposure: 147 weeks).	Docetaxel Participants received docetaxel 75 mg/m\^2 by IV infusion, once every 3 weeks (Q3W) until objective PD, unacceptable adverse event/toxicity, upon participant's request to stop treatment, or Investigator decision, whichever occurred first (maximum exposure: 115 weeks).
Overall Study Death	109	110
Overall Study Not related to Coronavirus disease 2019	0	1
Overall Study Withdrawal by Subject	1	7
Overall Study Ongoing study treatment at the time of primary analysis	36	25

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Tusamitamab Ravtansine n=194 Participants Participants received tusamitamab ravtansine 100 mg/m\^2 by IV infusion, once Q2W until objective PD, unacceptable adverse event/toxicity, upon participant's request to stop treatment, or Investigator decision, whichever occurred first (maximum exposure: 147 weeks).	Docetaxel n=195 Participants Participants received docetaxel 75 mg/m\^2 by IV infusion, once Q3W until objective PD, unacceptable adverse event/toxicity, upon participant's request to stop treatment, or Investigator decision, whichever occurred first (maximum exposure: 115 weeks).	Total n=389 Participants Total of all reporting groups
Age, Continuous	63.3 years STANDARD_DEVIATION 9.2 • n=5 Participants	62.3 years STANDARD_DEVIATION 9.8 • n=7 Participants	62.8 years STANDARD_DEVIATION 9.5 • n=5 Participants
Sex: Female, Male Female	71 Participants n=5 Participants	86 Participants n=7 Participants	157 Participants n=5 Participants
Sex: Female, Male Male	123 Participants n=5 Participants	109 Participants n=7 Participants	232 Participants n=5 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized Asian	54 Participants n=5 Participants	58 Participants n=7 Participants	112 Participants n=5 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized White	115 Participants n=5 Participants	94 Participants n=7 Participants	209 Participants n=5 Participants
Race/Ethnicity, Customized Not reported	22 Participants n=5 Participants	36 Participants n=7 Participants	58 Participants n=5 Participants
Race/Ethnicity, Customized Unknown	2 Participants n=5 Participants	5 Participants n=7 Participants	7 Participants n=5 Participants

PRIMARY outcome

Timeframe: Tumor assessments performed at screening, and every 8 weeks +/-5 days thereafter, up to 189 weeks

Population: The intent-to-treat (ITT) population consisted of all participants who had given their informed consent and who had a treatment kit number allocated and recorded in the IRT database.

Outcome measures

Outcome measures
Measure	Tusamitamab Ravtansine n=194 Participants Participants received tusamitamab ravtansine 100 mg/m\^2 by IV infusion, once Q2W until objective PD, unacceptable adverse event/toxicity, upon participant's request to stop treatment, or Investigator decision, whichever occurred first (maximum exposure: 147 weeks).	Docetaxel n=195 Participants Participants received docetaxel 75 mg/m\^2 by IV infusion, once Q3W until objective PD, unacceptable adverse event/toxicity, upon participant's request to stop treatment, or Investigator decision, whichever occurred first (maximum exposure: 115 weeks).
Progression-free Survival (PFS)	5.39 months Interval 3.713 to 6.998	5.85 months Interval 5.52 to 7.359

PRIMARY outcome

Timeframe: From date of first study treatment administration (Day 1) until the date of death due to any cause, up to 189 weeks

Population: The ITT population consisted of all participants who had given their informed consent and who had a treatment kit number allocated and recorded in the IRT database.

Overall survival was defined as the time from date of randomization to date of death due to any cause.

Outcome measures

Outcome measures
Measure	Tusamitamab Ravtansine n=194 Participants Participants received tusamitamab ravtansine 100 mg/m\^2 by IV infusion, once Q2W until objective PD, unacceptable adverse event/toxicity, upon participant's request to stop treatment, or Investigator decision, whichever occurred first (maximum exposure: 147 weeks).	Docetaxel n=195 Participants Participants received docetaxel 75 mg/m\^2 by IV infusion, once Q3W until objective PD, unacceptable adverse event/toxicity, upon participant's request to stop treatment, or Investigator decision, whichever occurred first (maximum exposure: 115 weeks).
Overall Survival (OS)	12.81 months Interval 11.795 to 14.16	11.53 months Interval 8.936 to 15.244

SECONDARY outcome

Timeframe: Tumor assessments performed at screening, and every 8 weeks +/-5 days thereafter, up to 189 weeks

Population: The ITT population consisted of all participants who had given their informed consent and who had a treatment kit number allocated and recorded in the IRT database. Only participants with randomization date ≥8 weeks prior to analysis cut-off date or with early PD prior to the cut-off date are reported.

ORR was defined as the percentage of participants who had a complete response (CR) or partial response (PR), as best overall response derived from overall response (OR) determined by the IRC per RECIST 1.1. CR was defined as disappearance of all target and non-target lesions, and normalization of tumor marker level. Any pathological lymph nodes (whether target or non-target) must have had 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.

Outcome measures

Outcome measures
Measure	Tusamitamab Ravtansine n=189 Participants Participants received tusamitamab ravtansine 100 mg/m\^2 by IV infusion, once Q2W until objective PD, unacceptable adverse event/toxicity, upon participant's request to stop treatment, or Investigator decision, whichever occurred first (maximum exposure: 147 weeks).	Docetaxel n=187 Participants Participants received docetaxel 75 mg/m\^2 by IV infusion, once Q3W until objective PD, unacceptable adverse event/toxicity, upon participant's request to stop treatment, or Investigator decision, whichever occurred first (maximum exposure: 115 weeks).
Objective Response Rate (ORR)	21.7 percentage of participants Interval 16.04 to 28.26	24.1 percentage of participants Interval 18.13 to 30.84

SECONDARY outcome

Timeframe: Predose on Day 1 of Cycle 1, then on Day 1 of every 2 docetaxel Cycles, or every 3 tusamitamab ravtansine Cycles (i.e., every 6 weeks) up to 30 days after the last dose of study drug administration, up to 151 weeks

Population: The ITT population consisted of all participants who had given their informed consent and who had a treatment kit number allocated and recorded in the IRT database.

The TTD was defined as the time from baseline (Cycle 1, Day 1) until the first ≥10-point change from baseline up to the end of treatment assessment before the initiation of further anticancer therapy and the analysis cut-off date. For the TTD in disease-related symptoms (cough, dyspnea, pain) from EORTC QLQ LC-13, a deterioration was defined as an increase from baseline score of at least 10 points in any 1 of these 3 symptoms. The EORTC QLQ-LC13 (LC13) is the lung cancer module of the EORTC QLQ-C30 that assesses lung-cancer-associated symptoms (cough, dyspnea, pain, hemoptysis) and side-effects from conventional chemotherapy and radiotherapy (sore mouth, hair loss, dysphagia and neuropathy). The EORTC QLQ-LC13 contains 13 items. Items on the LC13 were scored using the LC13 scoring algorithms which standardize the raw scores to a 0-100 range. Lower scores indicate lower symptomology/symptom burden (lower scores better).

Outcome measures

Outcome measures
Measure	Tusamitamab Ravtansine n=194 Participants Participants received tusamitamab ravtansine 100 mg/m\^2 by IV infusion, once Q2W until objective PD, unacceptable adverse event/toxicity, upon participant's request to stop treatment, or Investigator decision, whichever occurred first (maximum exposure: 147 weeks).	Docetaxel n=195 Participants Participants received docetaxel 75 mg/m\^2 by IV infusion, once Q3W until objective PD, unacceptable adverse event/toxicity, upon participant's request to stop treatment, or Investigator decision, whichever occurred first (maximum exposure: 115 weeks).
Time to Deterioration (TTD) in Disease-related Symptoms as Determined by European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire and Lung Cancer-specific Module With 13 Items (EORTC QLQ LC-13)	2.83 months Interval 2.103 to 4.304	1.87 months Interval 1.544 to 2.793

SECONDARY outcome

Population: The ITT population consisted of all participants who had given their informed consent and who had a treatment kit number allocated and recorded in the IRT database.

TTD was defined as time from baseline(Cycle 1,Day 1) until first ≥10-point change from baseline up to end of treatment assessment before initiation of further anticancer therapy and analysis cut-off date.For TTD in physical function from EORTC QLQ-C30, deterioration=decrease of at least 10 points from baseline score.EORTC QLQ-C30(C30) is 30-item, cancer specific that includes global health status/health-related quality of life(GHS/QoL), functional scales(physical,role,emotional,cognitive,social), symptom scales(fatigue,nausea\&vomiting,pain), 5 symptom items(dyspnea,insomnia,appetite loss,constipation,diarrhea,perceived financial difficulties). Most questions from QLQ-C30 were rated on 4-point scale(1/Not at All to 4/Very Much), except Items 29-30,which comprise GHS scale and were rated on 7-point scale(1/Very Poor to 7/Excellent). All scales were transformed from raw scores to linear scales ranging 0-100. High score represented favorable outcome with best quality of life.

Outcome measures

Outcome measures
Measure	Tusamitamab Ravtansine n=194 Participants Participants received tusamitamab ravtansine 100 mg/m\^2 by IV infusion, once Q2W until objective PD, unacceptable adverse event/toxicity, upon participant's request to stop treatment, or Investigator decision, whichever occurred first (maximum exposure: 147 weeks).	Docetaxel n=195 Participants Participants received docetaxel 75 mg/m\^2 by IV infusion, once Q3W until objective PD, unacceptable adverse event/toxicity, upon participant's request to stop treatment, or Investigator decision, whichever occurred first (maximum exposure: 115 weeks).
TTD in Physical Function as Determined by European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Cancer-specific Module With 30 Items (EORTC QLQ C30)	7.46 months Interval 5.552 to 15.211	4.17 months Interval 3.023 to 4.567

SECONDARY outcome

Population: The ITT population consisted of all participants who had given their informed consent and who had a treatment kit number allocated and recorded in the IRT database.

TTD was defined as time from baseline (Cycle 1, Day 1) until first ≥10-point change from baseline up to end of treatment assessment before initiation of further anticancer therapy and analysis cut-off date. For TTD in role function from EORTC QLQ-C30, deterioration = decrease of at least 10 points from baseline score. EORTC QLQ-C30 (C30) is a 30-item, cancer specific that includes GHS/QoL, functional scales (physical, role, emotional, cognitive, social), symptom scales (fatigue, nausea \& vomiting, pain), 5 symptom items (dyspnea, insomnia, appetite loss, constipation, diarrhea, perceived financial difficulties item). Most questions from QLQ-C30 were rated on a 4-point scale (1/Not at All to 4/Very Much), except Items 29-30, which comprise GHS scale and were rated on a 7-point scale (1/Very Poor to 7/Excellent). All scales were transformed from raw scores to linear scales ranging 0 to 100. A high score represented a favorable outcome with a best quality of life for participant.

Outcome measures

Outcome measures
Measure	Tusamitamab Ravtansine n=194 Participants Participants received tusamitamab ravtansine 100 mg/m\^2 by IV infusion, once Q2W until objective PD, unacceptable adverse event/toxicity, upon participant's request to stop treatment, or Investigator decision, whichever occurred first (maximum exposure: 147 weeks).	Docetaxel n=195 Participants Participants received docetaxel 75 mg/m\^2 by IV infusion, once Q3W until objective PD, unacceptable adverse event/toxicity, upon participant's request to stop treatment, or Investigator decision, whichever occurred first (maximum exposure: 115 weeks).
TTD in Role Function Measured by EORTC QLQ C30	5.55 months Interval 3.713 to 6.308	4.17 months Interval 2.793 to 4.37

SECONDARY outcome

Timeframe: From date of first study treatment administration (Day 1) up to 30 days after the last dose of study treatment administration, up to 151 weeks

An AE was any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. A SAE was defined as any untoward medical occurrence that, at any dose resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent disability/incapacity, was a congenital anomaly/birth defect, or was an important medical event. TEAEs were defined as AEs that developed, worsened, or became serious during the treatment period.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From date of first study treatment administration (Day 1) up to 30 days after the last dose of study treatment administration, up to 151 weeks

Blood samples were collected to determine the abnormalities in hematology parameters.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From date of first study treatment administration (Day 1) up to 30 days after the last dose of study treatment administration, up to 151 weeks

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

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Tumor assessments performed at screening, and every 8 weeks +/-5 days thereafter, up to 189 weeks

DOR was defined as the time from the date of first initial occurrence of a CR or PR to the date of first documentation of objective PD according to RECIST 1.1 before the initiation of any posttreatment anticancer therapy or death due to any cause, whichever occurred first. CR was defined as disappearance of all target and non-target lesions, and normalization of tumor marker level. Any pathological lymph nodes (whether target or non-target) must have had 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. PD was defined as unequivocal progression of existing non-target lesions; appearance of 1 or more new lesions; at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.

Outcome measures

Outcome measures
Measure	Tusamitamab Ravtansine n=41 Participants Participants received tusamitamab ravtansine 100 mg/m\^2 by IV infusion, once Q2W until objective PD, unacceptable adverse event/toxicity, upon participant's request to stop treatment, or Investigator decision, whichever occurred first (maximum exposure: 147 weeks).	Docetaxel n=45 Participants Participants received docetaxel 75 mg/m\^2 by IV infusion, once Q3W until objective PD, unacceptable adverse event/toxicity, upon participant's request to stop treatment, or Investigator decision, whichever occurred first (maximum exposure: 115 weeks).
Duration of Response (DOR)	11.07 months Interval 5.158 to 19.844	5.75 months Interval 4.074 to 7.326

Adverse Events

Tusamitamab Ravtansine

Serious events: 55 serious events

Other events: 159 other events

Deaths: 109 deaths

Docetaxel

Serious events: 68 serious events

Other events: 151 other events

Deaths: 110 deaths

Serious adverse events

Other adverse events

Additional Information

Trial Transparency Team

Sanofi aventis recherche & développement

Phone: 800-633-1610

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The Sponsor supports publication of clinical trial results but may request that investigators temporarily delay or alter publications in order to protect proprietary information. The Sponsor may also require that the results of multicenter studies be published only in their entirety and not as individual site data.
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