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)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Sanofi-Aventis Recherche & Developpement

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

12 May 2021 → 25 Dec 2024

Decision date (initial)

2024-10-15

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2023-509115-84-00

EudraCT number

2020-000035-50

WHO UTN

U1111-1233-9798

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Dose response, Safety, Efficacy, Pharmacokinetic

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 6

1. 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
2. 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
3. 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
4. To assess the antitumor activity of tusamitamab ravtansine in combination with pembrolizumab and platinum-based chemotherapy in the NSQ NSCLC population
5. 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)
6. 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

Conditions and MedDRA coding

Cancer

Regulatory references

EMA paediatric investigation plan (PIP)

EMEA-002504-PIP01-18

Plan to share IPD

Yes

IPD 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

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Histologically- or cytologically-confirmed diagnosis of advanced or metastatic NSQ NSCLC with no EGFR sensitizing mutation or BRAF mutation or ALK/ROS alterations.
2. 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).
3. Expression of CEACAM5 as demonstrated prospectively by a centrally assessed 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).
4. Measurable disease based on RECIST 1.1.
5. Eastern Cooperative Oncology Group (ECOG) performance status 0-1
6. Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies
7. Life expectancy of at least 3 months.

Exclusion criteria 27

1. Medical condition requiring concomitant administration of a medication with a strong CYP3A inhibitor.
2. 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.
3. 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.
4. Symptomatic herpes zoster within 3 months prior to screening.
5. Significant allergies to humanized monoclonal antibodies.
6. 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).
7. Concurrent treatment with any other anticancer therapy.
8. Have received prior chemotherapy treatment for advanced/metastatic NSCLC.
9. The patient is a candidate for a curative treatment with either surgical resection and/or chemoradiation
10. 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).
11. Any prior therapy targeting CEACAM5.
12. Uncontrolled brain metastases and history of leptomeningeal disease.
13. 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.
14. Any prior maytansinoid treatment (DM1 or DM4 ADC).
15. 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.
16. Any radiation therapy to lung >30 Gy within 6 months of first study intervention administration.
17. Has received or will receive a live vaccine within 30 days prior to the first study intervention administration.
18. Any major surgery within the preceding 3 weeks of the first study intervention administration.
19. Current participation in any other clinical study involving an investigational study treatment or any other type of medical research.
20. Poor organ function
21. 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.
22. 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.
23. History of known acquired immunodeficiency syndrome (AIDS) related illnesses or known HIV disease requiring antiretroviral treatment, or active hepatitis A, B, or C infection.
24. History of known acquired immunodeficiency syndrome (AIDS) related illnesses or known HIV disease requiring antiretroviral treatment, or active hepatitis A, B, or C infection.
25. History of allogeneic tissue/solid organ transplantation.
26. Active infection requiring IV systemic therapy within 2 weeks prior to randomization or active tuberculosis.
27. Interstitial lung disease or history of pneumonitis that has required oral or IV steroids

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Incidence of study drug-related dose-limiting toxicity (DLTs) at Cycle 1 (C1D1 to C1D21)
2. Expansion part (including participants treated at the recommended dose for expansion [RDE] from the Safety Run-in part): Objective response rate (ORR)

Secondary endpoints 7

1. Incidence of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), and laboratory abnormalities according to Common Terminology Criteria for Adverse Events (CTCAE) V5.0
2. Progression-free survival (PFS)
3. Disease control rate (DCR)
4. Duration of response (DOR)
5. ORR
6. Pharmacokinetic concentrations
7. Incidence of anti-therapeutic antibodies (ATAs) against tusamitamab ravtansine

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 5

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Sanofi-Aventis Recherche & Developpement

Sponsor organisation

Sanofi-Aventis Recherche & Developpement

Address

82 Avenue Raspail

City

Gentilly

Postcode

94250

Country

France

Scientific contact point

Organisation

Sanofi-Aventis Recherche & Developpement

Contact name

Clinical Sciences and Operations

Public contact point

Organisation

Sanofi-Aventis Recherche & Developpement

Contact name

Clinical Sciences and Operations

Third parties 5

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 14 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications