ER+ breast cancer gastric cancer lung cancer NSQ NSCLC
Conditions
Interventions
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
Sponsors
Erasmus MC, Universitair Medisch Centrum Rotterdam
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: • 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.
Exclusion criteria
Exclusion criteria: 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 for ocular toxicity, this should be grade 0 at baseline. This criteria does not apply to 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. • Any prior therapy targeting CEACAM5. • Prior maytansinoid DM4 treatment (ADC). • Unresolved corneal disorder or any previous corneal disorder considered by an ophthalmologist to predict high
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The primary outcome of the study is the intratumoral concentration of DM4 and the maximal tumor size deviation of the biopsied lesion according to Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secundary outcomes of the study are: - Intratumoral concentration of tusamitamab ravtansine and its metabolites (Lys-SPDB-DM4, Me-DM4) - Systemic concentration of tusamitamab ravtansine, DM4 and its metabolites - Toxicity - CEACAM5 expression at baseline compared to on-treatment - RNA expression levels and features of the tumor micro-environment at baseline compared to on-treatment - Tumor genomic features - Circulating CEA (carcino-embryonic antigen) levels | — |
Countries
Netherlands
Outcome results
None listed