Tusamitamab Ravtansine in NSQ NSCLC Participants With Negative or Moderate CEACAM5 Expression Tumors and High Circulating CEA (CARMEN-LC06)

• ClinicalTrials.gov Identifier: NCT05245071
• Recruitment Status: Active, not recruiting
• First Posted: February 17, 2022
• Last Update Posted: May 31, 2024
• Sponsor: Sanofi
• Information provided by (Responsible Party): Sanofi

Tracking Information

• First Submitted Date: February 9, 2022
• First Posted Date: February 17, 2022
• Last Update Posted Date: May 31, 2024
• Actual Study Start Date: June 1, 2022
• Actual Primary Completion Date: March 6, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 9, 2022)

Objective Response Rate (ORR) [ Time Frame: Baseline up to approximately 9 months after last patient treated ]

Objective Response Rate (ORR), defined as the proportion of participants who have a confirmed complete response (CR) or partial response (PR) as best overall response (BOR) per Response Evaluation Criteria In Solid Tumors (RECIST) v1.1

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: February 9, 2022)

• Incidence of participants with treatment-emergent adverse events (TEAEs), serious adverse events (SAEs) and laboratory abnormalities [ Time Frame: Baseline up to approximately 90 days after the last study treatment administration ]
  Incidence of participants with treatment-emergent adverse events (TEAEs), serious adverse events (SAEs) and laboratory abnormalities according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5.0
• Progression-free survival (PFS) [ Time Frame: Baseline up to approximately 9 months after last patient treated ]
  PFS defined as the time from the date of first tusamitamab ravtansine administration to the date of the first documented disease progression or death due to any cause, whichever comes first.
• Disease control rate (DCR) [ Time Frame: Baseline up to approximately 9 months after last patient treated ]
  DCR defined as the percentage of participants who have achieved confirmed CR or PR, or stable disease as BOR per RECIST v1.1
• Duration of response (DOR) [ Time Frame: Baseline up to approximately 9 months after last patient treated ]
  DOR, 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
• Incidence of participants with anti-therapeutic antibodies (ATAs) against tusamitamab ravtansine [ Time Frame: Baseline up to approximately 30 days after the last study treatment administration ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Tusamitamab Ravtansine in NSQ NSCLC Participants With Negative or Moderate CEACAM5 Expression Tumors and High Circulating CEA
• Official Title: Open-label, Phase 2 Study, Evaluating the Efficacy and Safety of Tusamitamab Ravtansine in Non-squamous Non-small-cell Lung Cancer (NSQ NSCLC) Participants With Negative or Moderate CEACAM5 Expression Tumors and High Circulating CEA

Brief Summary

This is an open label single group, Phase 2, 1-arm study for treatment to evaluate efficacy, safety, and Pharmacokinetic (PK) of tusamitamab ravtansine in nonsquamous non-small-cell-lung-cancer (NSQ NSCLC) participants with negative or moderate CEACAM5 expression tumors and high circulating carcinoembryonic antigen (CEA).

Participants who will be enrolled, will receive tusamitamab ravtansine as monotherapy every two weeks (Q2W) until disease progression, unacceptable adverse event (AE), initiation of a new anticancer therapy, or the participant's or investigator's decision to stop the treatment, whichever comes first. A total of approximately 38 participants are planned to be treated.

• Detailed Description: 40 weeks (up to 4 weeks for screening, a median of 24 weeks for treatment, and a median of 12 weeks for end of treatment assessments and the safety follow-up visit).
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Non-squamous Non-small Cell Lung Cancer

Intervention

Drug: Tusamitamab ravtansine

Pharmaceutical Form: Concentrate for solution Route of Administration: Intravenous infusion

Other Name: SAR408701

Study Arms

Experimental: Tusamitamab ravtansine

Tusamitamab ravtansine dose will be administered on Day 1 via IV infusion and repeated once every 2 weeks. The duration of 1 cycle will be 14 days (1 administration of tusamitamab ravtansine per cycle).

Intervention: Drug: Tusamitamab ravtansine

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: February 8, 2024): 22
• Original Estimated Enrollment (submitted: February 9, 2022): 38
• Estimated Study Completion Date: September 2, 2024
• Actual Primary Completion Date: March 6, 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Histologically or cytologically proven diagnosis of NSQ NSCLC metastatic disease at study entry; progression after platinum-based chemotherapy and immune checkpoint inhibitor.
• Participants with moderate or negative CEACAM5 expression as demonstrated prospectively by central laboratory via immune histochemistry (ICH) and high circulating CEA levels (≥100 ng/mL). Moderate CEACAM5 expression is defined as intensity ≥ 2 + in ≥ 1% and <50 % of tumor cells. Negative CEACAM5 expression is defined as intensity of 1 + whatever the percentage of stained tumor cells or <1% of tumor cells.
• At least one measurable lesion by RECIST v1.1
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
• Women of childbearing potential or male patient with women of childbearing potential who agree to use highly effective method of birth control.

Exclusion Criteria:

• Patients with untreated brain metastases or history of leptomeningeal disease.
• 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 uncontrolled infection with human immunodeficiency virus (HIV), or unresolved viral hepatitis
• Significant concomitant illness that could impair the participation in the study or interpretation of the results or any major surgery with 3 weeks prior treatment administration
• Nonresolution 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.
• Previous history of and/or unresolved corneal disorders. The use of contact lenses is not permitted.
• Prior treatment with maytansinoid derivatives (DM1 or DM4 antibody drug conjugate) or any drug targeting CEACAM5.
• Concurrent treatment with any other anticancer therapy
• Poor bone marrow, liver or kidney functions.

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Belgium, France, Italy, Japan, Spain, Turkey, United States

Administrative Information

• NCT Number: NCT05245071
• Other Study ID Numbers: ACT17241; U1111-1264-2828 ( Registry Identifier: ICTRP ); 2021-004423-32 ( EudraCT Number )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: 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

• Current Responsible Party: Sanofi
• Original Responsible Party: Same as current
• Current Study Sponsor: Sanofi
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Clinical Sciences & Operations; Sanofi

• PRS Account: Sanofi
• Verification Date: May 2024