Clinical trial NCT04659603: Tusamitamab Ravtansine Monotherapy and in Combination in Patients With CEACAM5-positive Advanced Solid Tumors
Official title: Open-label, Multi-cohort, Phase 2 Trial, Evaluating the Efficacy and Safety of Tusamitamab Ravtansine (SAR408701) Monotherapy and in Combination in Patients With CEACAM5-positive Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Breast Cancer Metastatic
Pancreatic Carcinoma Metastatic
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2020-12-09
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Primary Objective:

* For Cohort A, Cohort B, and Cohort C Part 2: To assess the antitumor activity of tusamitamab ravtansine in metastatic breast cancer (mBC) and tusamitamab ravtansine monotherapy and in combination with gemcitabine in metastatic pancreatic adenocarcinoma (mPAC)
* For Cohort C Part 1: Confirmation of the recommended tusamitamab ravtansine dose when administered in combination with gemcitabine

Secondary Objectives:

* To assess the safety and tolerability of tusamitamab ravtansine administered as monotherapy and in combination with gemcitabine
* To assess other efficacy parameters of tusamitamab ravtansine administered as monotherapy and in combination with gemcitabine
* To assess the immunogenicity of tusamitamab ravtansine
* To assess the pharmacokinetics (PK) of tusamitamab ravtansine and gemcitabine when given in combination

Detailed description: The expected duration of study intervention for participants may vary, based on progression date and the cohort; median expected duration of study per participant is estimated at 8 months for Cohort A/C and 6 months for Cohort B (up to 1 month for screening, a median of 4 or 2 months for treatment in Cohort A/C and Cohort B respectively, a median of 1 month for EOT, and follow-up visit 90 days after the last IMP administration).

Eligibility criteria: Inclusion Criteria:

* Participant must be at least 18 years of age
* Participants with at least one measurable lesion according to the RECIST v1.1 criteria that has not been irradiated (ie, newly arising lesions in previously irradiated areas are accepted).
* Participants with ECOG performance status 0 to 1.
* Evidence of metastatic disease.
* Expression of CEACAM 5 by centrally assessed IHC assay.
* Male and female participants willing to comply with contraceptive use consistent with local regulations regarding the methods of contraception for those participating in clinical studies.

Cohort A: mBC

* Histological or cytologic diagnosis of breast cancer.
* Have received at least 2 prior cytotoxic chemotherapy regimens for non-TNBC tumor type or at least 1 for TNBC tumor type but not more than 4 in the locally recurrent or metastatic setting.

Cohorts B and C: mPAC

- Have confirmed diagnosis of pancreatic ductal adenocarcinoma.

Cohort B: mPAC:

- Have documented radiographic progression or documented intolerance after at least 1 prior systemic chemotherapy line which included either gemcitabine (or relapsed within 6 months of completion of gemcitabine adjuvant therapy) or a 5-fluorouracil based regimen (including capecitabine) but no more than 2 prior chemotherapy lines for locally advanced/metastatic disease.

Cohort C: mPAC

- Have documented radiographic progression or documented intolerance after 1st line fluoropyrimidine-containing chemotherapy (or relapsed within 6 months of completion of chemotherapy as adjuvant therapy) for locally advanced/metastatic disease.

Exclusion Criteria:

Participants are excluded from the study if any of the following criteria apply:

* Medical condition requiring concomitant administration of a medication with a narrow therapeutic window, that is metabolized by cytochrome P450 (CYP450), and for which a dose reduction cannot be considered.
* Medical conditions requiring concomitant administration of strong CYP3A inhibitor, unless it can be discontinued at least 2 weeks before the first administration of study intervention.
* Life expectancy less than 3 months.
* Untreated brain metastases or history of leptomeningeal disease.
* Significant concomitant illness
* 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 human immunodeficiency virus (HIV) disease requiring antiretroviral treatment, or active hepatitis A, B or C infection.
* 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 (HRT).
* Unresolved corneal disorder or any previous corneal disorder considered by an ophthalmologist to predict higher risk of drug-induced keratopathy.
* Use of contact lenses. Participants using contact lenses who are not willing to stop wearing them for the duration of the study intervention are excluded.
* Concurrent treatment with any other anti cancer therapy.
* 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 prior antitumor therapy (chemotherapy, targeted agents, immunotherapy and radiotherapy, or any investigational treatment).
* Any prior therapy targeting CEACAM5.
* Prior maytansinoid DM4 treatment (ADC).
* Any major surgery within the preceding 2 weeks of the first study intervention administration.
* Previous enrollment in this study or current participation in any other clinical study involving an investigational study treatment or any other type of medical research.
* Poor renal function
* Poor hepatic function
* Poor bone marrow function

Cohort C: mPAC

- Any previous systemic therapy with taxane or gemcitabine (for Cohort C only).

The above information is not intended to contain all considerations relevant to the potential participation in a clinical trial.

Primary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: From date of first study treatment administration (Day 1) up to maximum exposure of treatment: 26.1 weeks (Cohort A), 51.6 weeks (Cohort B), 43.3 weeks (Cohort C)
measure: Cohort C (Part 1): Number of Participants With Dose Limiting Toxicities (DLTs)
timeFrame: Cycle 1 (28 days)
Secondary outcomes:
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)
timeFrame: From date of first study treatment administration (Day 1) up to primary completion date of 16 February 2024, up to 150 weeks
measure: Number of Participants With Laboratory Abnormalities: Hematology/Coagulation and Clinical Chemistry
timeFrame: From date of first study treatment administration (Day 1) up to primary completion date of 16 February 2024, up to 150 weeks
measure: Progression-free Survival (PFS)
timeFrame: From date of first study treatment administration (Day 1) up to maximum exposure of treatment: 26.1 weeks (Cohort A), 51.6 weeks (Cohort B), 43.3 weeks (Cohort C)
measure: Disease Control Rate (DCR)
timeFrame: From date of first study treatment administration (Day 1) up to maximum exposure of treatment: 26.1 weeks (Cohort A), 51.6 weeks (Cohort B), 43.3 weeks (Cohort C)
measure: Duration of Response (DOR)
timeFrame: From date of first study treatment administration (Day 1) up to maximum exposure of treatment: 26.1 weeks (Cohort A), 51.6 weeks (Cohort B), 43.3 weeks (Cohort C)
measure: Number of Participants With Treatment-emergent Anti-therapeutic Antibodies (ATAs) Against Tusamitamab Ravtansine
timeFrame: From date of first study treatment administration (Day 1) up to 30 days after the last dose of study treatment administration [maximum exposure of treatment: 26.1 weeks (Cohort A), 51.6 weeks (Cohort B), 43.3 weeks (Cohort C)]
measure: Cohort C: Maximum Concentration Observed After Infusion (Cmax) of Tusamitamab Ravtansine
timeFrame: Cycle 1: Day 1: start of infusion (SOI), end of infusion (EOI), EOI+3 hours, and 72, 168, 336 hours post-SOI (cycle duration: 28 days)
measure: Cohort C: Area Under the Plasma Concentration Versus Time Curve Calculated Using the Trapezoidal Method From Time 0 to 14 Days (AUC0-14d) of Tusamitamab Ravtansine
timeFrame: Cycle 1: Day 1: start of infusion (SOI), end of infusion (EOI), EOI+3 hours, and 72, 168, 336 hours post-SOI (cycle duration: 28 days)
measure: Cohort C: Total Body Clearance From Plasma (CL) of Gemcitabine
timeFrame: Cycle 1: Days 1 and 8: start of infusion (SOI), end of infusion (EOI), EOI+0.25 hours, and 1, 1.5, 2 hours post-SOI (cycle duration: 28 days)
measure: Cohort C: Cmax of Gemcitabine Metabolite (dFdU)
timeFrame: Cycle 1: Days 1 and 8: start of infusion (SOI), end of infusion (EOI), EOI+0.25 hours, and 1, 1.5, 2 hours post-SOI (cycle duration: 28 days)
Other outcomes:
Locations:
city: Orlando
country: United States
facility: AdventHealth Orlando Site Number : 8400001
state: Florida
city: Boston
country: United States
facility: Massachusetts General Hospital Site Number : 8400002
state: Massachusetts
city: Madison
country: United States
facility: University of Wisconsin Site Number : 8400004
state: Wisconsin
city: Capital Federal
country: Argentina
facility: Investigational Site Number : 0320003
state: Buenos Aires
city: Pergamino
country: Argentina
facility: Investigational Site Number : 0320001
state: Buenos Aires
city: Rosario
country: Argentina
facility: Investigational Site Number : 0320002
state: Santa Fe
city: Temuco
country: Chile
facility: Investigational Site Number : 1520002
state: La Araucanía
city: Santiago
country: Chile
facility: Investigational Site Number : 1520003
state: Reg Metropolitana De Santiago
city: Santiago
country: Chile
facility: Investigational Site Number : 1520001
state: Reg Metropolitana De Santiago
city: Budapest
country: Hungary
facility: Investigational Site Number : 3480003
city: Goyang-si
country: Korea, Republic of
facility: Investigational Site Number : 4100003
state: Gyeonggi-do
city: Seoul
country: Korea, Republic of
facility: Investigational Site Number : 4100001
state: Seoul-teukbyeolsi
city: Seoul
country: Korea, Republic of
facility: Investigational Site Number : 4100002
state: Seoul-teukbyeolsi
city: Amsterdam
country: Netherlands
facility: Investigational Site Number : 5280002
city: Rotterdam
country: Netherlands
facility: Investigational Site Number : 5280001
city: Utrecht
country: Netherlands
facility: Investigational Site Number : 5280003
city: Moscow
country: Russian Federation
facility: Investigational Site Number : 6430001
city: Pushkin, Saint- Petersburg
country: Russian Federation
facility: Investigational Site Number : 6430004
city: Saint -Petersburg
country: Russian Federation
facility: Investigational Site Number : 6430002
city: Barcelona
country: Spain
facility: Investigational Site Number : 7240001
state: Barcelona [Barcelona]
city: Madrid
country: Spain
facility: Investigational Site Number : 7240003
state: Madrid, Comunidad De
city: Majadahonda
country: Spain
facility: Investigational Site Number : 7240002
state: Madrid
city: Taichung
country: Taiwan
facility: Investigational Site Number : 1580001
city: Tainan
country: Taiwan
facility: Investigational Site Number : 1580002
city: Taipei
country: Taiwan
facility: Investigational Site Number : 1580003
city: Adana
country: Turkey
facility: Investigational Site Number : 7920003
city: Ankara
country: Turkey
facility: Investigational Site Number : 7920004
city: Istanbul
country: Turkey
facility: Investigational Site Number : 7920001
city: Izmir
country: Turkey
facility: Investigational Site Number : 7920002
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References: