INTRUSION: Unraveling the INTRatUmoral PK/PD relatION for SAR408701

NCT05703555 | Withdrawn Phase 2

• 2 other identifiers: INTRUSION2022-003451-34
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

This study is a prospective, open-label, multi-cohort, exploratory phase II clinical trial in patients with either CEACAM5-positive NSQ NSCLC, ER+ breast cancer or gastric cancer. Eligible subjects will receive Tusamitamab ravtansine (100mg/m2 IV Q2W). The investigators hypothesize that intratumoral exposure of Tusamitamab ravtansine would be an important factor in determining treatment efficacy. Combining exposure with measurements of tumor PD reactions in a proper PK/PD study is the goal of this study.

Conditions

Metastatic Lung Cancer; Metastatic Breast Cancer; Metastatic Gastric Cancer

Keywords

tusamitamab ravtansine; CEACAM5; Pharmacokinetics

Outcome Measures

Primary Outcomes (1)

• intratumoral DM4 concentration

  Intratumoral DM4 exposure, as measured in a biopsied lesion using a PK assay.

  approximately 5 weeks, more specific day 3 of cycle 2 (each cycle is 14 days)

Secondary Outcomes (16)

• Intratumoral tusamitamab ravtansine concentration

  approximately 5 weeks, more specific day 3 of cycle 2 (each cycle is 14 days)

• Incidence of grade 3 or 4 adverse events

  during treatment (up to 2 years and 12 weeks)

• Response to treatment

  every 8 weeks during treatment (up to 2 years and 12 weeks)

• CEACAM5 expression

  approximately 5 weeks, more specific day 3 of cycle 2 (each cycle is 14 days)

• RNA expression levels

  approximately 5 weeks, more specific day 3 of cycle 2 (each cycle is 14 days)

Study Arms (1)

Tusamitamab ravtansine 100mg/m2

EXPERIMENTAL

Tusamitamab ravtansine 100 mg/m2 IV Q2W

Drug: Tusamitamab ravtansine

Interventions

Tusamitamab ravtansine DRUG

Eligible subjects will receive Tusamitamab ravtansine (100mg/m2 IV Q2W). Subjects without evidence of disease progression or drug related toxicity can continue treatment with Tusamitamab ravtansine (100 mg/m2 IV Q2W) until disease progression, unacceptable toxicity occurs, or the participant's or Investigator's decision to stop the treatment.

Also known as: SAR408701

Tusamitamab ravtansine 100mg/m2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult patients (≥ 18y) at the time of signing the Informed Consent Form (ICF).
• Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1
• Estimated life expectancy ≥ 3 months
• Expression of CEACAM5 established by an IHC assay of ≥2+ in intensity involving at least 50% of the tumor cell population in archival tumor sample (or, if not available, a fresh biopsy sample) at a metastatic site (mandatory) including distant lymph nodes.
• Either: Metastatic or irresectable Non-Squamous Non-Small Cell Lung Cancer without EGFR/ALK/ROS aberration, as diagnosed by histological evaluation, after chemotherapy (restricted to 1 line of platinum-based chemotherapy) and immunotherapy (not more than 1 line). These therapies may have been applied concurrent or sequential; Or: Metastatic ER+ breast cancer, pathologically confirmed. ER+ is defined as ≥1% tumor staining by IHC. Participants must be no longer eligible for hormonal therapy. Participants may have had at maximum 1 prior systemic chemotherapy line.
• A chemotherapy line in advanced/metastatic disease is an anti-cancer regimen that contains at least 1 cytotoxic chemotherapy agent and was discontinued due to progression. If a cytotoxic chemotherapy regimen was discontinued for a reason other than disease progression then this regimen does not count as a "prior line of chemotherapy" unless this regimen was discontinued after at least 2 cycles of treatment.
• Or: Metastatic gastric cancer, pathologically confirmed, with no regular treatment options left and having received all standard of care treatments.
• Metastatic lesion accessible for repeated biopsy and willingness to undergo sequential biopsies.
• Lesion to be biopsied must be measurable on CT according to RECIST v1.1.
• Ability and willingness to give written informed consent and to comply with the requirements of the study.

You may not qualify if:

• Medical conditions:
• 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.
• Symptomatic or untreated brain metastases or history of leptomeningeal disease. Participants with previously treated brain metastases may participate provided that:
• i. metastases are stable for at least 4 weeks according to imaging and symptoms returned to baseline; ii. there is no evidence of new or enlarging brain metastases; iii. the participant does not require any corticosteroids to manage brain metastases within 3 weeks prior to the first dose of study intervention.
• Recent (within 6 months) Pulmonary Embolism or other recent (within 6 months) thromboembolic event requiring anticoagulant therapy.
• Ascites requiring palliative intervention such as repeated drainage.
• Prior toxicity incurred as a result of previous anti-cancer therapy (radiation therapy, chemotherapy, or surgery) that have not resolved to ≤ grade 2 according to NCI-CTCAE version 5.0 \[Appendix 3\] except ocular toxicity, this should be grade 0 at baseline, without the exception of alopecia, vitiligo, or active thyroiditis controlled with hormone replacement therapy.
• Major surgical procedure (including open biopsy and excluding central line intravenous catheter) within 28 days prior to Cycle 1 Day 1, or anticipation of the need for major surgery during the course of the study treatment.
• History of human immunodeficiency virus (HIV) antibody positive or use of antiretroviral therapy. No HIV testing is required unless mandated by local health authority.
• Medical conditions requiring concomitant administration of strong CYP3A inhibitor or inducer unless it can be discontinued at least 2 weeks before the first administration of study intervention and discontinued for the duration of the study intervention.
• Unable or unwilling to stop the use of (herbal) supplements which can strongly induce or inhibit CYP3A, including grapefruit containing food or juice or St. John's Wort from 2 weeks before the first Tusamitamab ravtansine administration up to the last Tusamitamab ravtansine administration.
• Medical condition requiring concomitant administration of medication with a narrow therapeutic window that is metabolized by cytochrome P450 (CYP450) from 2 weeks before the first Tusamitamab ravtansine administration up to the last Tusamitamab ravtansine administration. See also section 5.2.
• Specific Tusamitamab ravtansine (SAR408701) related conditions:
• Less than 4 weeks or less than 5 times the half-life, whichever is shorter, since the last treatment of chemotherapy, biological therapy, immunotherapy or systemic radiotherapy (except palliative radiation delivered to \<20% of bone marrow), before Cycle 1 Day 1.
• Current or recent (within 4 weeks prior to Cycle 1 Day 1) treatment with another Investigational Product or participation in another investigational interventional study.

Sponsors & Collaborators

• Erasmus Medical Center: lead
• Sanofi: collaborator

Study Sites (1)

Erasmus MC

Rotterdam, 3015GD, Netherlands

Location

MeSH Terms

Conditions

Lung Neoplasms; Breast Neoplasms; Stomach Neoplasms

Interventions

tusamitamab ravtansine

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases

Study Officials

• Debbie Robbrecht, Dr.

  Erasmus Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: open-label, multi-cohort

Study Record Dates

• First Submitted: December 13, 2022
• First Posted: January 30, 2023
• Study Start: February 16, 2024
• Primary Completion: February 16, 2024
• Study Completion: February 16, 2024
• Last Updated: February 28, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: Within 12 months of last visit of last patient

Locations

NL (1)