Tusamitamab Ravtansine (SAR408701) in Combination With Pembrolizumab and Tusamitamab Ravtansine (SAR408701) in Combination With Pembrolizumab and Platinum-based Chemotherapy With or Without Pemetrexed in Patients With NSQ NSCLC (CARMEN-LC05)

Sanofi

Status and phase

Terminated

Phase 2

Conditions

Non-squamous Non-small-cell Lung Cancer (NSQ NSCLC)

Treatments

Drug: Cisplatin

Drug: SAR408701 (Tusamitamab ravtansine)

Drug: Pemetrexed

Drug: Pembrolizumab

Drug: Carboplatin

Study type

Interventional

Funder types

Industry

Identifiers

NCT04524689

2023-509115-84 (Registry Identifier)

U1111-1233-9798 (Registry Identifier)

ACT16146

Details and patient eligibility

About

Primary Objective:

Safety run-in part: to assess the tolerability and to determine the recommended doses of tusamitamab ravtansine in combination with pembrolizumab and tusamitamab ravtansine in combination with pembrolizumab and platinum-based chemotherapy with or without pemetrexed to be tested in the expansion part of the study in the NSQ NSCLC population
Expansion part (including participants treated at the recommended dose for expansion [RDE] from the Safety Run-in part): to assess the antitumor activity of several dose levels (DLs; if applicable) of tusamitamab ravtansine in combination with pembrolizumab and of several DLs of tusamitamab ravtansine in combination with pembrolizumab, platinum-based chemotherapy, and pemetrexed in the NSQ NSCLC population

Secondary Objectives:

To assess the safety and tolerability of several DLs (if applicable) of tusamitamab ravtansine in combination with pembrolizumab and of 1 DL of tusamitamab ravtansine in combination with pembrolizumab and platinum-based chemotherapy, and of several DLs of tusamitamab ravtansine in combination with pembrolizumab, and platinum-based chemotherapy with pemetrexed in the NSQ NSCLC population
To assess the antitumor activity of several DLs (if applicable) of tusamitamab ravtansine in combination with pembrolizumab and of 1 DL of tusamitamab ravtansine in combination with pembrolizumab and platinum-based chemotherapy, and of several DLs of tusamitamab ravtansine in combination with pembrolizumab, platinum-based chemotherapy, and pemetrexed in the NSQ NSCLC population
To assess the durability of the response to treatment with several DLs (if applicable) of tusamitamab ravtansine in combination with pembrolizumab and of 1 DL of tusamitamab ravtansine in combination with pembrolizumab and platinum-based chemotherapy, and of several DLs of tusamitamab ravtansine in combination with pembrolizumab and platinum-based chemotherapy, and pemetrexed in the NSQ NSCLC population
To assess the antitumor activity of tusamitamab ravtansine in combination with pembrolizumab and platinum-based chemotherapy in the NSQ NSCLC population
To assess the pharmacokinetics (PK) of tusamitamab ravtansine, pembrolizumab, pemetrexed, cisplatin, and carboplatin, each when given in combination as a doublet (tusamitamab ravtansine + pembrolizumab) or a triplet (tusamitamab ravtansine + pembrolizumab + platinum-based chemotherapy) or a quadruplet (tusamitamab ravtansine + pembrolizumab + platinum-based chemotherapy + pemetrexed)
To assess the immunogenicity of tusamitamab ravtansine in combination with pembrolizumab and tusamitamab ravtansine in combination with pembrolizumab and platinum based chemotherapy with or without pemetrexed

Full description

The expected duration of study intervention for participants may vary, based on disease progression date; median expected duration of study per participant is estimated at 10 months (up to 1 month for screening, a median of 6 months for treatment, a median of 1 month for EOT, and follow-up visit 90 days after the last IMP administration).

Enrollment

57 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion 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 1% 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
Life expectancy of at least 3 months

Exclusion criteria:

Medical condition requiring concomitant administration of a medication with a strong CYP3A 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.

Trial design

Primary purpose

Treatment

Allocation

Non-Randomized

Interventional model

Parallel Assignment

Masking

None (Open label)

57 participants in 6 patient groups

Tusamitamab ravtasine 150 mg/m^2 + Pembrolizumab

Experimental group

Description:

Pembrolizumab dose will be administered intravenously prior to intravenous administration of tusamitamab ravtansine dose every 3 weeks.

Treatment:

Drug: Pembrolizumab

Drug: SAR408701 (Tusamitamab ravtansine)

Tusamitamab ravtasine 170 mg/m^2 + Pembrolizumab

Experimental group

Description:

Pembrolizumab dose will be administered intravenously prior to intravenous administration of tusamitamab ravtansine dose every 3 weeks.

Treatment:

Drug: Pembrolizumab

Drug: SAR408701 (Tusamitamab ravtansine)

Tusamitamab ravtansine 150 mg/m^2 + Pembrolizumab + carboplatin or cisplatin

Experimental group

Description:

Pembrolizumab dose will be administered intravenously prior to intravenous adminstration of tusamitamab ravtansine dose every 3 weeks. Carboplatin will be infused over 15 to 60 minutes immediately after tusamitamab ravtansine infusion on Day 1 and Q3W for the first 4 cycles. Cisplatin will be infused approximately 30 minutes after tusamitamab ravtansine infusion on Day 1 and Q3W for the first 4 cycles.

Treatment:

Drug: Carboplatin

Drug: Pembrolizumab

Drug: SAR408701 (Tusamitamab ravtansine)

Drug: Cisplatin

Tusamitamab ravtansine 170 mg/m^2 + Pembrolizumab + carboplatin or cisplatin

Experimental group

Description:

Treatment:

Drug: Carboplatin

Drug: Pembrolizumab

Drug: SAR408701 (Tusamitamab ravtansine)

Drug: Cisplatin

Tusamitamab ravtansine 150 mg/m^2 + Pembrolizumab + carboplatin or cisplatin + pemetrexed

Experimental group

Description:

Pembrolizumab dose will be administered intravenously prior to intravenous adminstration of tusamitamab ravtansine dose every 3 weeks. Pemetrexed will be infused over 10 minutes after tusamitamab ravtansine infusion on Day 1 and then Q3W. Carboplatin will be infused over 15 to 60 minutes immediately after pemetrexed infusion on Day 1 and Q3W for the first 4 cycles. Cisplatin will be infused approximately 30 minutes after pemetrexed infusion after pemetrexed infusion on Day 1 and Q3W for the first 4 cycles.

Treatment:

Drug: Carboplatin

Drug: Pembrolizumab

Drug: Pemetrexed

Drug: SAR408701 (Tusamitamab ravtansine)

Drug: Cisplatin

Tusamitamab ravtansine 170 mg/m^2 + Pembrolizumab + carboplatin or cisplatin + pemetrexed

Experimental group

Description:

Treatment:

Drug: Carboplatin

Drug: Pembrolizumab