An Open-Label Phase 1/2 Trial to Evaluate the Safety, Tolerability, and Efficacy of MORAb 202 in Subjects with Selected Tumor Types.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Eisai Limited

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

28 Feb 2023 → ongoing

Decision date (initial)

2024-02-09

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Eisai Ltd and Eisai Inc

External identifiers

EU CT number

2023-506868-14-00

EudraCT number

2019-003600-12

WHO UTN

U1111-1298-8560

ClinicalTrials.gov

NCT04300556

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

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

Dose-Escalation: To evaluate safety, tolerability and to determine the RP2D of MORAb-202 (IP) in subjects with OC, EC, NSCLC, TNBC.
Dose-Confirmation Part: To further evaluate the safety and tolerability of IP. To evaluate preliminary efficacy measured by objective response rate (ORR) of IP in subjects with OC and EC at selected doses.
To determine the recommended treatment regimen for further development of IP.
Dose-Optimization Part:
Part A (OC and EC):
To evaluate other IP treatment regimens for safety, tolerability, and preliminary efficacy in subjects with OC and EC.
To evaluate the addition of a short course (3 days) of oral corticosteroids 1 week following every dose of MORAb-202 administered every 21 days,
To select treatment regimens with IP for further evaluation in Part B.
Part B (OC only):
To evaluate the safety, tolerability of different doses of IPs monotherapy and in combination with lenvatinib and to determine the recommended dose (RD) of IP as monotherapy and in combination with lenvatinib for further evaluation

Secondary objectives 1

1. To evaluate the relationship between folate receptor alpha (FRA) expression levels in tumor tissue and clinical outcome measures. To evaluate DOR, DCR and CBR and in part B OC to evaluate Objective Response Rate (ORR) of MORAb-202 as monotherapy and in combination with lenvatinib To evaluate PFS and OS To determine the PK profiles of MORAb-202 , total Ab and released eribulin in serum or plasma To determine PK profiles of lenvatinib when given in combination with MORAb-202

Conditions and MedDRA coding

Solid tumors in 4 tumor types: platinum resistant ovarian cancer, triple-negative breast cancer (TNBC), endometrial cancer (EC), and non-small cell lung cancer adenocarcinoma; NSCLC).

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 2

1. 1.Aged ≥18 years 2.For Dose-Escalation: Females (TNBC, EC and OC) or males/females (NSCLC adenocarcinoma) as defined in the protocol. For Dose-Confirmation and Dose Optimization: OC: High-grade serous ovarian cancer or primary peritoneal cancer or fallopian tube cancer. Subjects must have platinum-resistant disease (as defined in the protocol and have received up to 3 prior lines of systemic therapy and for whom single-agent therapy is appropriate as the next line of therapy. Subjects may have been treated with up to one line of therapy subsequent to determination of platinum-resistance. In Dose Optimization Part B subjects may have received up to 3 prior lines of systemic therapy, up to 4 prior lines is permitted for subjects who have received prior mirvetuximab soravtansine. EC: Histologically confirmed diagnosis of advanced, recurrent, or metastatic EC. All histologies (including carcinosarcoma [no more than one subject per dose level]) and molecular subtypes will be included. Subjects may have been treated with an immune checkpoint inhibitor containing regimen (or be ineligible for ICI treatment) and must have had no more than 2 prior regimens Note: Only subjects with histologically confirmed diagnosis of advanced, recurrent, or metastatic EC will be enrolled at sites in France. In dose Optimization Part B only OC subjects will be enrolled. 3.Available tumor tissue for FRA expression (%) by IHC analysis as assessed at a central lab. In dose Optimization Part B for subjects who have received prior treatment with mirvetuximab soravtansine will be required to provide a fresh biopsy sample during screening. 4.Radiological disease progression on or after the most recent therapy by investigator assessment. 5.Measurable disease as set out in the protocol 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. 10.Adequate liver function as defined in the protocol
2. 11.Who must undergo a washout period requirement following prior anticancer treatment defined in the protoco 12. With a history of deep vein thrombosis (DVT) within 3 months of enrollment must be on a stable dose of anticoagulation as demonstrated by appropriate laboratory parameters (depending on the anticoagulant agent) for a minimum of 2 weeks before starting study treatment. Anticoagulation must continue while on the study treatment. 13.At risk for DVT secondary to central venous catheters or with past medical history of DVT or clinical symptoms suggestive of DVT must have venous Doppler ultrasonography to rule out DVT during the screening period and before initiation of study treatment. 14.Who have undergone major surgery, the subject must have recovered adequately from the toxicity and/or complications from the intervention before prior to starting study treatment. 15.Resolution of anticancer therapy-related or radiation-related toxicities to Grade 1 severity or lower, except for stable sensory neuropathy (Grade ≤2), anemia (Hgb ≥9.0 g/dL), and alopecia (any grade). 16. Must be willing and able to comply with all aspects of the protocol. 17. Must provide written informed consent prior to any study-specific screening procedures. 18.For Dose optimization Part B (only applicable to cohorts where MORAb-202 is used in combination with lenvatinib): Have adequately controlled BP with or without antihypertensive medications, defined as BP ≤150/90 mm Hg and no change in antihypertensive medications within 1 week before first administration of the study drug.

Exclusion criteria 3

1. 1 Have endometrial leiomyosarcoma, endometrial stromal sarcoma other soft tissue sarcoma histology. 2-Received previous treatment with any folate receptor targeting agents,except for mirvetuximab soravtansine in the setting of FRA ≥75%. 3- Have platinum refractory OC. 4-Currently enrolled in another clinical study or used any investigational drug or device as defined in the protocol. 5- With brain or subdural metastases (as defined in the protocol) 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 before prior to starting study treatment. 8-Significant cardiovascular impairment. 9-Clinically significant ECG abnormality. 10-Known to be 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. 13-Females of childbearing potential who: -within 28 days before study entry, did not use a highly effective method of contraception, as set out in the protocol. -do not agree to use a highly effective method of contraception (as set out in the protocol) throughout the entire study period and for 7 months after study drug discontinuation. 14-For Dose-Escalation only: Males who have not had a successful vasectomy or they and their female partners do not meet the criteria above (refer to the protocol). 15-Pulmonary Function Test (PFT) abnormalities: FEV1/FVC <0.7, FEV1 or FVC <80%, DLCO <80%or less than the lower limit of normal according to local institutional standards. 16-Current ILD/pneumonitis, or ILD/pneumonitis is suspected at Screening or history of ILD/pneumonitis of any severity including ILD/pneumonitis from prior anticancer therapy. 17-Current infectious pneumonia, history of viral pneumonia with evidence of persistent radiologic abnormalities. 18-Lung-specific clinically significant illnesses and restrictive lung disease or currently receiving any medication that is associated with a clinically significant risk of developing ILD. 19-Clinically significant pleural or pericardial effusion requiring drainage or ascites requiring peritoneal shunt. 20-Prior pneumonectomy.
2. 21-History of chest radiotherapy. Subjects with history of chest wall radiation (eg, history of breast cancer) may be permitted if chest wall radiation is documented > 2 years before starting study treatment. 22-Any autoimmune, connective tissue, or inflammatory disorders where there is documented (or suspicion of) pulmonary involvement. 23-A known history of active TB (bacillus tuberculosis). 24-Scheduled for surgery during the study, other than minor surgery which would not delay study treatment. 25-An active clinically significant (in the opinion of the Investigator) infection requiring systemic therapy within 2 weeks before the first dose of study drug. 26-Administration of a live, attenuated vaccine within 4 weeks before the first dose of study drug, or anticipation that such a live attenuated vaccine will be required during the study. 27-Any prior hypersensitivity to monoclonal antibodies and/or contraindication to the receipt of corticosteroids or any of the excipients 28-Known intolerance to either of the components of the study drug. 29-Any medical or other condition which, in the opinion of the investigator would preclude the subject's participation in the clinical study. 30-Receiving any medication prohibited in combination with the study treatment(s), as described in the product label for eribulin, unless medication was stopped within 7 days before enrollment. 31-Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
3. In addition, for Dose Optimization Part B subjects who receive MORAb-202 in combination with Lenvatinib: 32. If >1+ proteinuria on dipstick, 24-hour urine protein is ≥1 g 33. Gastrointestinal malabsorption or any other condition that might affect the absorption of lenvatinib. 34. Unable to take oral medication. 35. Major surgery within 3 weeks before the first dose of study treatment. 36. Have a serious nonhealing wound, ulcer or bone fracture. 37. Pre-existing Grade ≥3 gastrointestinal (GI) or non-GI fistula. 38.Subjects having radiographic evidence of major blood vessel invasion/infiltration.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. RP2D of MORAb-202 (Dose-Escalation Part only).For Dose Optimization Part B: RD of MORAb-202 IV monotherapy and in combination with Lenvatinib.
2. ORR: defined as the proportion of subjects achieving a best overall response (BOR) of complete response (CR) or partial response (PR) (BOR - are CR, PR, SD, PD, and not evaluable (NE), where SD has to be achieved at ≥5 weeks after the first dose. All responses of CR and PR must be confirmed no less than 28 days following the initial achievement of the response.
3. Safety Endpoints: DLTs, AEs,(SAEs, AEs leading to treatment discontinuation),AEs leading to dose interruption/reduction and AEIs (including ILD incidence, severity, duration and outcome, and deaths).

Secondary endpoints 1

1. DOR, DCR, CBR, PFS by RECIST 1.1, and OS. Safety Endpoints: clinical laboratory tests, vital signs, oxygen saturation, body weight, 12-lead ECGs, ECOG PS, and The PK profiles of MORAb-202/total antibody/released eribulin in serum or plasma. The relationship between FRA expression levels in tumor tissue and clinical outcome.

Investigational products

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

Test 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Eisai Limited

Sponsor organisation

Eisai Limited

Address

European Knowledge Center, Mosquito Way Mosquito Way

City

Hatfield

Postcode

AL10 9SN

Country

United Kingdom

Scientific contact point

Organisation

Eisai Limited

Contact name

Medical Information

Public contact point

Organisation

Eisai Limited

Contact name

Medical Information

Third parties 20

Locations

2 EU/EEA countries · 15 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

Documents 8 files

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

Application history

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