Description:
Primary Objectives:
- Part A - Part 1 (safety run-in): To assess the tolerability and to determine the
recommended dose of tusamitamab ravtansine in combination with pembrolizumab in the NSQ
NSCLC population
- Part A - Part 2: To assess the anti-tumor activity of tusamitamab ravtansine in
combination with pembrolizumab in the NSQ NSCLC population
- Part B: To assess the tolerability and to determine the recommended doses of tusamitamab
ravtansine in combination with pembrolizumab and platinum-based chemotherapy in the NSQ
NSCLC population
Secondary Objectives:
- To assess the safety and tolerability of tusamitamab ravtansine in combination with
pembrolizumab and tusamitamab ravtansine in combination with pembrolizumab and
platinum-based chemotherapy
- To assess the durability of the response to treatment with tusamitamab ravtansine in
combination with pembrolizumab
- To assess the efficacy on progression-free survival (PFS) of tusamitamab ravtansine in
combination with pembrolizumab
- To assess the pharmacokinetics (PK) of tusamitamab ravtansine, pembrolizumab, cisplatin,
and carboplatin, each when given in combination as a doublet (tusamitamab ravtansine +
pembrolizumab) or triplet (tusamitamab ravtansine + pembrolizumab + platinum-based
chemotherapy
- To assess the immunogenicity of tusamitamab ravtansine when given in combination with
pembrolizumab and in combination with pembrolizumab and platinum-based chemotherapy
- To assess the antitumor activity of tusamitamab ravtansine in combination with
pembrolizumab and platinum-based chemotherapy in the NSQ NSCLC population
Title
- Brief Title: Tusamitamab Ravtansine (SAR408701) in Combination With Pembrolizumab and Tusamitamab Ravtansine (SAR408701) in Combination With Pembrolizumab and Platinum-based Chemotherapy in Patients With NSQ NSCLC (CARMEN-LC05)
- Official Title: Open-label, Phase 2 Study of Tusamitamab Ravtansine (SAR408701) Combined With Pembrolizumab and Tusamitamab Ravtansine (SAR408701) Combined With Pembrolizumab and Platinum-based Chemotherapy in Patients With CEACAM5 Positive Advanced/Metastatic Non-squamous Non-small-cell Lung Cancer (NSQ NSCLC)
Clinical Trial IDs
- ORG STUDY ID:
ACT16146
- SECONDARY ID:
U1111-1233-9798
- NCT ID:
NCT04524689
Conditions
- Non-squamous Non-small-cell Lung Cancer (NSQ NSCLC)
Interventions
Drug | Synonyms | Arms |
---|
SAR408701 (Tusamitamab ravtansine) | Tusamitamab ravtansine | Tusamitamab ravtasine + Pembrolizumab |
Pembrolizumab | Keytruda | Tusamitamab ravtasine + Pembrolizumab |
Cisplatin | | Tusamitamab ravtasine + Pembrolizumab + either carboplatin or carboplatin |
Carboplatin | | Tusamitamab ravtasine + Pembrolizumab + either carboplatin or carboplatin |
Purpose
Primary Objectives:
- Part A - Part 1 (safety run-in): To assess the tolerability and to determine the
recommended dose of tusamitamab ravtansine in combination with pembrolizumab in the NSQ
NSCLC population
- Part A - Part 2: To assess the anti-tumor activity of tusamitamab ravtansine in
combination with pembrolizumab in the NSQ NSCLC population
- Part B: To assess the tolerability and to determine the recommended doses of tusamitamab
ravtansine in combination with pembrolizumab and platinum-based chemotherapy in the NSQ
NSCLC population
Secondary Objectives:
- To assess the safety and tolerability of tusamitamab ravtansine in combination with
pembrolizumab and tusamitamab ravtansine in combination with pembrolizumab and
platinum-based chemotherapy
- To assess the durability of the response to treatment with tusamitamab ravtansine in
combination with pembrolizumab
- To assess the efficacy on progression-free survival (PFS) of tusamitamab ravtansine in
combination with pembrolizumab
- To assess the pharmacokinetics (PK) of tusamitamab ravtansine, pembrolizumab, cisplatin,
and carboplatin, each when given in combination as a doublet (tusamitamab ravtansine +
pembrolizumab) or triplet (tusamitamab ravtansine + pembrolizumab + platinum-based
chemotherapy
- To assess the immunogenicity of tusamitamab ravtansine when given in combination with
pembrolizumab and in combination with pembrolizumab and platinum-based chemotherapy
- To assess the antitumor activity of tusamitamab ravtansine in combination with
pembrolizumab and platinum-based chemotherapy in the NSQ NSCLC population
Detailed Description
The expected duration of the study intervention for participants may vary based on
progression date; median expected duration of study per participant is estimated 10 months
(up to 1 month for screening, a median of 6 months for treatment, and a median of 3 months
for end-of-treatment assessments and safety follow-up visit).
Trial Arms
Name | Type | Description | Interventions |
---|
Tusamitamab ravtasine + Pembrolizumab | Experimental | Part A:
-Part 1 (Safety run-in): Pembrolizumab dose will be administered intravenously prior to intravenous administration of tusamitamab ravtasine dose every 3 weeks.
-Part 2: Pembrolizumab dose will be administered intravenously prior to intravenous administration of tusamitamab ravtasine dose every 3 weeks. The dose of tusamitamab ravtansine will be selected based on the outcome of Part 1 of Part A. | - SAR408701 (Tusamitamab ravtansine)
- Pembrolizumab
|
Tusamitamab ravtasine + Pembrolizumab + either carboplatin or carboplatin | Experimental | Pembrolizumab dose will be administered intravenously prior to intravenous adminstration of tusamitamab ravtasine dose every 3 weeks. Cisplatin or carboplatin dose should be infused approximately 30 minutes after tusamitamab ravtasine infusion on Day 1 and then Q3W for the first 4 cycles. | - SAR408701 (Tusamitamab ravtansine)
- Pembrolizumab
- Cisplatin
- Carboplatin
|
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 50% 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
- Capable of giving signed informed consent
Exclusion criteria:
- Medical condition requiring concomitant administration of a medication with a narrow
therapeutic window and metabolized by CYP450 or a strong CTP3A 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.
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Part A Part 1 and Part B: Number of participants with study drug-related dose-limiting toxicity (DLTs) at Cycle 1 (C1D1 to C1D21) |
Time Frame: | Baseline up to 10 months after last participant treated |
Safety Issue: | |
Description: | Study drug-related dose-limiting toxicity (DLTs) at Cycle 1 (C1D1 to C1D21), including but not limited to corneal toxicity. Each cycle is 21 days. |
Secondary Outcome Measures
Measure: | Number of participants with treatment-emergent adverse events (TEAEs), serious adverse events (SAEs) and laboratory abnormalities |
Time Frame: | Baseline up to 10 months after last participant treated |
Safety Issue: | |
Description: | TEAEs, SAEs and laboratory abnormalities according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) V5 - |
Measure: | Part A: Duration of response |
Time Frame: | Baseline up to 10 months after last participant treated |
Safety Issue: | |
Description: | Duration of response (DOR), defined as the time from first documented evidence of CR or PR until progressive disease determined per RECIST 1.1 or death from any cause, whichever occurs first |
Measure: | Part A: Progression-free survival |
Time Frame: | Baseline up to 10 months after last participant treated |
Safety Issue: | |
Description: | Progression-free survival, defined as the time from the date of randomization to the date of the first documented disease progression or death due to any cause, whichever comes first |
Measure: | Ceoi of tusamitamab ravtansine and pembrolizumab |
Time Frame: | At cycle 1. Each cycle is 21 days |
Safety Issue: | |
Description: | Concentration observed at the end of IV infusion (Ceoi) of tusamitamab ravtansine and pembrolizumab when given in combination and Ceoi of pembrolizumab when given alone |
Measure: | Cmax of tusamitamab ravtansine, pembrolizumab, Cisplatin, and carboplatin |
Time Frame: | At cycle 1. Each cycle is 21 days |
Safety Issue: | |
Description: | Maximum concentration observed after infusion (Cmax) of tusamitamab ravtansine, pembrolizumab, cisplatin and carboplatin when given in combination and of pembrolizumab when given alone |
Measure: | Tmax of tusamitamab ravtansine, pembrolizumab, cisplatin and carboplatin |
Time Frame: | At cycle 1. Each cycle is 21 days |
Safety Issue: | |
Description: | Time to reach Cmax (Tmax) of tusamitamab ravtansine, pembrolizumab, cisplatin and carboplatin when given in combination and of pembrolizumab when given alone |
Measure: | Clast of tusamitamab ravtansine and pembrolizumab |
Time Frame: | At cycle 1. Each cycle is 21 days |
Safety Issue: | |
Description: | Clast concentration observed above the lower limit of quantification after infusion (Clast)of tusamitamab ravtansine and pembrolizumab when given in combination and Ceoi of pembrolizumab when given alone |
Measure: | Tlast of tusamitamab ravtansine and pembrolizumab |
Time Frame: | At cycle 1. Each cycle is 21 days |
Safety Issue: | |
Description: | Time of Clast (Tlast) of tusamitamab ravtansine and pembrolizumab when given in combination and Ceoi of pembrolizumab when given alone |
Measure: | Ctrough of tusamitamab ravtansine and pembrolizumab |
Time Frame: | Pembrolizumab: Cycle 1, 2, 4 and 8 tusamitamab ravtansine: Cycle 1, 2, 3, 4, 5, 6, 7, 8 and 13. Each cycle is 21 days |
Safety Issue: | |
Description: | Concentration observed just before treatment administration during repeated dosing (Ctrough) of tusamitamab ravtansine and pembrolizumab when given in combination and Ceoi of pembrolizumab when given alone |
Measure: | AUC0-21d of tusamitamab ravtansine and pembrolizumab |
Time Frame: | At cycle 1. Each cycle is 21 days |
Safety Issue: | |
Description: | Area under the plasma concentration versus time curve calculated using the trapezoidal method from time 0 to 21 days (AUC 0-21d) of SAR408701 and pembrolizumab when given in combination and Ceoi of pembrolizumab when given alone |
Measure: | AUC0-72h of cisplatin or carboplatin |
Time Frame: | At cycle 1. Each cycle is 21 days |
Safety Issue: | |
Description: | Area under the plasma concentration versus time curve calculated using the trapezoidal method from time 0 to 72 hours of cisplatin or carboplatin |
Measure: | Incidence of anti-therapeutic antibodies (ATAs) against tusamitamab ravtansine |
Time Frame: | At cycle 1, 2, 3, 4,6, 8 then every 5 cycles and end of treatment. Each cycle is 21 days |
Safety Issue: | |
Description: | Incidence of anti-therapeutic antibodies (ATAs) against tusamitamab ravtansine |
Measure: | Objective response rate (ORR) of tusamitamab ravtansine + pembrolizumab + platinum based chemotherapy |
Time Frame: | Baseline up to 10 months after last participant treated |
Safety Issue: | |
Description: | ORR is defined as proportion of participants who have a confirmed complete response (CR) or partial response (PR) as per RECIST v1.1 |
Details
Phase: | Phase 2 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | Sanofi |
Last Updated
August 5, 2021