A Multicenter, Open-Label Phase 1/2 Trial to Assess the Safety, Tolerability and the Efficaciousness of MORAb-202, which is a type of drug called antibody-drug conjugate (ADC) that targets folate receptor alpha (FRa) in subjects with selected tumor types
- Conditions
- Solid tumors expressing folate receptor alpha in 4 tumor types: platinum resistant ovarian cancer, triple-negative breast cancer (TNBC), endometrial cancer (EC), and non-small cell lung cancer adenocarcinomaNSCLC).MedDRA version: 20.0Level: PTClassification code 10033128Term: Ovarian cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 20.0Level: PTClassification code 10075566Term: Triple negative breast cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 21.0Level: PTClassification code 10014733Term: Endometrial cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 21.1Level: PTClassification code 10061873Term: Non-small cell lung cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2019-003600-12-FR
- Lead Sponsor
- Eisai Limited
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 55
1. Aged =18 years
2. For Dose-Escalation: Females (TNBC, EC and OC) or males/females (NSCLC adenocarcinoma). Subjects with the following disease characteristics:
a. TNBC:
Histologically confirmed diagnosis of metastatic TNBC (ie, estrogen receptor (ER) negative/progesterone receptor negative/ human epidermal growth factor receptor 2 (HER2) negative (defined as IHC <2+ or fluorescence in situ hybridization (FISH) negative) breast cancer). Previously treated with at least one line of systemic anticancer therapy (cytotoxic or targeted anticancer agents) in the metastatic setting.
b. NSCLC adenocarcinoma:
Histologically or cytologically confirmed metastatic NSCLC adenocarcinoma: subjects who have failed previous treatment for metastatic disease, are not indicated or failed epidermal growth factor receptor (EGFR)-, ALK-, BRAF- or ROS1-targeted therapy, and for whom no alternative standard therapy exists
c. EC:
Histologically confirmed diagnosis of advanced, recurrent or metastatic EC. Relapsed or failure of at least one platinum-based regimen or one immunotherapy-based regimen.
d. Ovarian cancer or primary peritoneal cancer or fallopian tube cancer:
Histologically confirmed diagnosis of high grade serous epithelial OC or primary peritoneal cancer or fallopian tube cancer.
Subjects must have:
platinum-resistant disease (defined as progression within 6 months after the last dose of at least 4 cycles of the last platinum containing chemotherapy regimen) received up to 4 lines of systemic therapy post development of platinum resistance.
For Dose-Confirmation:
-Ovarian cancer or primary peritoneal cancer or fallopian tube cancer.
-EC: Histologically confirmed diagnosis of advanced, recurrent, or metastatic EC.
3. Available tumor tissue for FRA expression (%) by IHC analysis as assessed by the vendor
4. Radiological disease progression on or after the most recent therapy by investigator assessment.
5. Measurable disease meeting the following criteria (confirmed by central radiographic review, in the Dose-Confirmation Part only):
- At least one lesion of >1.0 cm in long axis diameter for non-lymph nodes or >1.5 cm in short axis diameter for lymph nodes that is serially measurable according to Response Evaluation Criteria in Solid Tumors (RECIST) v 1.1 using either CT or MRI,
- Lesions that have had external beam radiotherapy (EBRT) or loco-regional therapies such as radiofrequency (RF) ablation must show evidence of PD based on RECIST 1.1 to be deemed a target lesion.
6. Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1.
7. Subjects who are expected to survive a minimum of 3 months after the first administration of the study drug.
8. Adequate renal function as defined in the protocol .
9. Adequate bone marrow function as defined in the protocol.
Growth factors or transfusions, as per institutional practice, are allowed if needed to achieve the above values. Growth factor and platelet transfusion should not be used within 7 days of initiation of study treatment.
10. Adequate liver function as defined in the protocol
11. Subjects must undergo a washout period required from the end of prior treatment to the first administration of the study drug.
12. Patients with a history of deep vein thrombosis (DVT) within 3 months prior must have completed at least 1 month of anticoagulation prior to starting study treatment
13.Patients at risk for DVT secondary to central venous catheters or with pas
1-Subjects with endometrial leiomyosarcoma, endometrial stromal sarcoma or high-grade sarcoma.
2-Subjects who received previous treatment with any folate receptor targeting agents.
3-Subjects with platinum refractory OC
4- Currently enrolled in another clinical study or used any investigational drug or device.
5-Subjects with brain or subdural metastases are not eligible, unless they have completed local therapy and have discontinued the use of corticosteroids for this indication for at least 2 weeks before starting treatment in this study.
6-Diagnosed with meningeal carcinomatosis.
7-Any other invasive malignancy that required treatment (other than definitive surgery) or has shown evidence of recurrence/progression (except for non-melanoma skin cancer, or histologically confirmed complete excision of carcinoma in situ) during the 2 years prior to starting study treatment.
8-Significant cardiovascular impairment.
9-Clinically significant ECG abnormality.
10-Known to be Human Immunodeficiency Virus (HIV) positive.
11-Active viral hepatitis (B or C as demonstrated by positive serology).
12-Females who are breastfeeding or pregnant at Screening or Baseline. A separate baseline assessment is required if a negative screening pregnancy test was obtained more than 72 hours before the first administration of the study drug.
13-Females of childbearing potential who:
•within 28 days before study entry, did not use a highly effective method of contraception, which includes any of the following:
•total abstinence (if it is their preferred and usual lifestyle)*
•an intrauterine device or intrauterine hormone-releasing system (IUS)
•a contraceptive implant
•an oral contraceptive (subject must be on a stable dose of the same oral contraceptive product for at least 28 days before dosing and throughout the study and for 90 days after study drug discontinuation)
•have a vasectomized partner with confirmed azoospermia
•do not agree to use a highly effective method of contraception (as described above) throughout the entire study period and for 90 days after study drug discontinuation.
14- For Dose-Escalation only: Males who have not had a successful vasectomy (confirmed azoospermia) or they and their female partners do not meet the criteria above (ie, not of childbearing potential or practicing highly effective contraception throughout the study period and for 90 days after study drug discontinuation). If the female partner is pregnant, then males who do not agree to use latex or synthetic condoms throughout the study period and for 90 days after study drug discontinuation. No sperm donation is allowed during the study period and for 90 days after study drug discontinuation.
15-Pulmonary Function Test (PFT) abnormalities: FEV1/FVC <0.7, FEV1 or FVC <80%, DLCO <80%.
16-Current ILD/pneumonitis, or ILD/pneumonitis is suspected at Screening or history interstitial lung disease (ILD)/pneumonitis of any severity including ILD/pneumonitis from prior anticancer therapy.
17-Current infectious pneumonia, history of viral pneumonia (including COVID-19–related infection) with evidence of persistent radiologic abnormalities.
18-Lung-specific clinically significant illnesses and restrictive lung disease.
19-Clinically significant pleural or pericardial effusion requiring drainage or ascites requiring peritoneal shunt.
20-Prior pneumonectomy.
21- History of chest radiotherapy. Subjects with history of chest wall
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method