SAR408701 in Combination With Pembrolizumab and Pembrolizumab Alone in Patients With Non-squamous Non-small Cell Lung Cancer (NSQ NSCLC) (CARMEN-LC05)

• ClinicalTrials.gov Identifier: NCT04524689
• Recruitment Status: Recruiting
• First Posted: August 24, 2020
• Last Update Posted: December 8, 2020
• Sponsor: Sanofi
• Information provided by (Responsible Party): Sanofi

Study Description

Brief Summary:

Primary Objectives:

• Part 1 (safety run-in): To assess the tolerability and to confirm the recommended dose of SAR408701 in combination with pembrolizumab in the NSQ NSCLC population
• Part 2: To assess the antitumor activity of SAR408701 in combination with pembrolizumab and pembrolizumab single agent in the NSQ NSCLC population

Secondary Objective:

• To assess the safety and tolerability of SAR408701 in combination with pembrolizumab and pembrolizumab single agent
• To assess the durability of the response to treatment with SAR408701 in combination with pembrolizumab and pembrolizumab single agent
• To assess the efficacy on progression-free survival (PFS) of SAR408701 in combination with pembrolizumab and pembrolizumab single agent
• To assess the pharmacokinetics (PK) of SAR408701 and pembrolizumab when given in combination, and of pembrolizumab when given as a single agent
• To assess the immunogenicity of SAR408701 when given in combination with pembrolizumab

Condition or disease	Intervention/treatment	Phase
Non-squamous Non-small-cell Lung Cancer (NSQ NSCLC)	Drug: SAR408701; Drug: Pembrolizumab	Phase 2

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 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).

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 54 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Randomized, Open-label, Phase 2 Study of SAR408701 Combined With Pembrolizumab and Pembrolizumab Alone in Patients With CEACAM5 and PD-L1 Positive Advanced/Metastatic Non-squamous Non-small-cell Lung Cancer (NSQ NSCLC)
• Actual Study Start Date: October 26, 2020
• Estimated Primary Completion Date: August 2022
• Estimated Study Completion Date: April 2023

Arms and Interventions

Arm	Intervention/treatment
Experimental: SAR408701 + Pembrolizumab; Pembrolizumab will be administered intravenously prior to intravenously adminstration of SAR408701 every 3 weeks	Drug: SAR408701; Pharmaceutical form:Concentrate for solution for infusion Route of administration: Intravenous; Drug: Pembrolizumab; Pharmaceutical form:Concentrate for solution for infusion Route of administration: Intravenous
Active Comparator: Pembrolizumab; Pembrolizumab - Pembrolizumab will be administered intravenously every 3 weeks. - Type:	Drug: Pembrolizumab; Pharmaceutical form:Concentrate for solution for infusion Route of administration: Intravenous

Outcome Measures

Primary Outcome Measures :

1. Part 1: 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 ]
   Study drug-related dose-limiting toxicity (DLTs) at Cycle 1 (C1D1 to C1D21), including but not limited to corneal toxicity
2. Part 2: Objective response rate (ORR) of SAR408701 + pembrolizumab and pembrolizumab single agent - [ Time Frame: Baseline up to 10 months after last participant treated ]
   ORR is defined as proportion of participants who have a confirmed complete response (CR) or partial response (PR) as per response evaluation criteria in solid tumors (RECIST v1.1)

Secondary Outcome Measures :

1. 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 ]
   TEAEs, SAEs and laboratory abnormalities according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) V5 -
2. Duration of response [ Time Frame: Baseline up to 10 months after last participant treated ]
   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
3. Progression-free survival [ Time Frame: Baseline up to 10 months after last participant treated ]
   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
4. Ceoi of SAR408701 and pembrolizumab [ Time Frame: Baseline up to 10 months after last participant treated ]
   Concentration observed at the end of IV infusion (Ceoi) of SAR408701 and pembrolizumab when given in combination and Ceoi of pembrolizumab when given alone
5. Cmax of SAR408701 and pembrolizumab [ Time Frame: Baseline up to 10 months after last participant treated ]
   Maximum concentration observed after infusion (Cmax) of SAR408701 and pembrolizumab when given in combination and Ceoi of pembrolizumab when given alone
6. Tmax of SAR408701 and pembrolizumab [ Time Frame: Baseline up to 10 months after last participant treated ]
   Time to reach Cmax (Tmax) of SAR408701 and pembrolizumab when given in combination and Ceoi of pembrolizumab when given alone
7. Clast of SAR408701 and pembrolizumab [ Time Frame: Baseline up to 10 months after last participant treated - ]
   Clast concentration observed above the lower limit of quantification after infusion (Clast)of SAR408701 and pembrolizumab when given in combination and Ceoi of pembrolizumab when given alone
8. Tlast of SAR408701 and pembrolizumab [ Time Frame: Baseline up to 10 months after last participant treated - ]
   Time of Clast (Tlast) of SAR408701 and pembrolizumab when given in combination and Ceoi of pembrolizumab when given alone
9. Ctrough of SAR408701 and pembrolizumab [ Time Frame: Baseline up to 10 months after last participant treated ]
   Concentration observed just before treatment administration during repeated dosing (Ctrough) of SAR408701 and pembrolizumab when given in combination and Ceoi of pembrolizumab when given alone
10. AUC0-21d of SAR408701 and pembrolizumab [ Time Frame: Baseline up to 10 months after last participant treated - 11. Baseline up to end of study (approximately 2 years) - ]
    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
11. Incidence of anti-therapeutic antibodies (ATAs) against SAR408701 [ Time Frame: Baseline up to end of study (approximately 2 years) ]
    Incidence of anti-therapeutic antibodies (ATAs) against SAR408701

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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).
• PD-L1 positive tumor (TPS ≥1%) as determined locally by an approved test
• 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.
• Untreated 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 longer, 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.

Contacts and Locations

Contacts

Contact: Trial Transparency email recommended (Toll free number for US & Canada); 800-633-1610 ext option 6; Contact-US@sanofi.com

Locations

Australia

Investigational Site Number 0360001; Recruiting

Heidelberg West, Australia, 3081

Investigational Site Number 0360003; Recruiting

Macquarie Park, Australia, 2109

Chile

Investigational Site Number 1520002; Recruiting

Santiago, Chile, 7500713

Investigational Site Number 1520001; Recruiting

Santiago, Chile, 8420383

Investigational Site Number 1520003; Recruiting

Viña Del Mar, Chile, 2520598

France

Investigational Site Number 2500003; Recruiting

Brest, France, 29200

Investigational Site Number 2500001; Recruiting

Pessac, France, 33604

Investigational Site Number 2500004; Recruiting

Poitiers Cedex, France, 86021

Hungary

Investigational Site Number 3480002; Recruiting

Budapest, Hungary, 1122

Investigational Site Number 3480004; Recruiting

Farkasgyepü, Hungary, 8582

Spain

Investigational Site Number 7240001; Recruiting

Madrid, Spain, 28041

Investigational Site Number 7240003; Recruiting

Valencia, Spain, 46010

Sponsors and Collaborators

Sanofi

Investigators

• Study Director: Clinical Sciences & Operations; Sanofi

More Information

• Responsible Party: Sanofi
• ClinicalTrials.gov Identifier: NCT04524689
• Other Study ID Numbers: ACT16146; U1111-1233-9798 ( Other Identifier: UTN )
• First Posted: August 24, 2020
• Last Update Posted: December 8, 2020
• Last Verified: December 2020

Individual Participant Data (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://www.clinicalstudydatarequest.com/

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Pembrolizumab; Antineoplastic Agents, Immunological; Antineoplastic Agents