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Clinical Trial 20497

Cancer Type: Gynecological Tumor
Study Type: Treatment
NCT#: NCT04300556

Phase: Phase I/II
Principal Investigator: Wenham, Robert

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or 1-800-679-0775 Learn More

Overview

Study Title

A Multicenter, Open-Label Phase 1/2 Trial Evaluating the Safety, Tolerability and Efficacy of MORAb-202, a Folate Receptor Alpha (FRA)-Targeting Antibody-Drug Conjugate (ADC) in Subjects with Selected Tumor Types

Summary

The primary objectives of the study are: (1) in the dose-escalation part: to evaluate safety, tolerability and to determine the recommended Phase 2 dose (RP2D) of MORAb-202, and (2) in an expansion part: to evaluate the objective response rate (ORR) in each of the selected tumor types at the RP2D.

Objective

Dose Escalation Primary Objective: To evaluate safety, tolerability and to determine the recommended Phase 2 dose (RP2D) of MORAb-202 in subjects with selected tumor types. Expansion Part Primary Objectives: To evaluate the objective response rate (ORR) in each of the selected tumor types at the RP2D. To further evaluate the safety and tolerability of MORAb-202. Secondary Objectives: To evaluate duration of response (DOR), disease control rate (DCR), and clinical benefit rate (CBR) in each tumor type. To evaluate progression-free survival (PFS) and overall survival (OS) in each tumor type. To determine the pharmacokinetic (PK) profiles of MORAb-202, total antibody, and released eribulin in serum and plasma in the tumor types combined. To evaluate the relationship between folate receptor alpha (FRA) expression levels and clinical outcome measures to support the identification of an appropriate FRA cut off point for each tumor type. Exploratory Objectives: To explore potential blood and tumor pharmacodynamics (PD) biomarkers (eg, soluble FRA), and correlate with clinical outcome measures including PK, safety, and efficacy. To investigate the effect of MORAb-202 on ventricular repolarization (Dose-Escalation Part only). To evaluate the PD effects and predictive biomarkers of MORAb-202 by examining genomic DNA, RNA, serum, plasma, circulating tumor cells (CTCs), urine, or archived tumor tissue to identify molecular or other biomarkers for therapy response. To evaluate the relationship between lines of prior therapy and clinical outcome measures (ovarian cancer only).

Treatments

Therapies

Therapy (NOS)

Medications

MORAb-202 ()

Inclusion Criteria

Aged 18 years of age or older

Females (Triple-negative breast cancer [TNBC], endometrial and ovarian cancer) or males/females (NSCLC, adenocarcinoma). Participants with the following disease characteristics as indicated in protocol.

Participants must have: (a) 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) (b) received up to 4 lines of systemic therapy post development of platinum resistance.

FRA-positive tumors (in the Expansion Part only). FRA expression to be assessed by immunohistochemistry (IHC) at a central laboratory using formalin-fixed, paraffin-embedded (FFPE) tissue samples. FRA positivity is defined as membrane staining in >=5% of neoplastic cells at any intensity level.

Available tumor tissue for FRA expression analysis. Either archival paraffin-embedded formalin-fixed (FFPE) tissue or newly obtained biopsies are acceptable if obtained under standard of care.

Radiological disease progression on or after the most recent therapy by investigator assessment.

Measureable disease meeting the following criteria (confirmed by central radiographic review, in the Expansion Part only): (a) At least one lesion of greater than (>) 1.0 centimeter (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) 1.1 using either computed tomography (CT) or magnetic resonance imaging (MRI), (b) 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.

ECOG PS of 0 or 1.

Participants who are expected to survive a minimum of 3 months after the first administration of the study drug.

Adequate renal function, bone marrow function and liver function.

Participants must undergo a washout period required from the end of prior treatment to the first administration of the study drug as outlined per protocol.

If a participant has undergone major surgery, the participant must have recovered adequately from the toxicity and/or complications from the intervention prior to starting study treatment.

Resolution of anticancer therapy-related or radiation-related toxicities to Grade 1 severity or lower, except for stable sensory neuropathy (Grade =9.0 g/dL), and alopecia (any grade).

Participant must be willing and able to comply with all aspects of the protocol.

Additional criteria will apply

Exclusion Criteria

Participants who received previous treatment with any folate receptor targeting agents.

Participants with platinum refractory ovarian cancer (defined as disease progression during the initial platinum-based chemotherapy treatment).

Currently enrolled in another clinical study or used any investigational drug or device, which in the opinion of the Sponsor may interfere with the study treatment, within the past 28 days or 5 times the half-life (where prior drug therapy falls under the parameters these Inclusion Criteria should be followed) of any investigational drug preceding informed consent.

Participants 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 4 weeks before starting treatment in this study. Any signs (example, radiologic) or symptoms of brain metastases must be stable for at least 4 weeks before starting study treatment.

Diagnosed with meningeal carcinomatosis.

Any other 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.

Significant cardiovascular impairment. History within 6 months prior to the first dose of study drug of: congestive heart failure greater than New York Heart Association (NYHA) Class II); unstable angina; myocardial infarction; stroke; cardiac arrhythmia associated with hemodynamic instability.

Clinically significant ECG abnormality, including marked prolonged baseline QT as corrected using Fridericia's formula (QTcF) (repeated demonstration of a QTcF interval >500 ms). A history of risk factors for torsade de pointes (example, heart failure, hypokalemia, family history of long QT Syndrome) or the use of concomitant medications that prolong the QTcF.

Previously known to be Human Immunodeficiency Virus (HIV) positive. Testing at entry not required.

Active viral hepatitis (B or C as demonstrated by positive serology).

Females who are breastfeeding or pregnant at Screening or Baseline (as documented by a positive beta human chorionic gonadotropin [ß-hCG] or human chorionic gonadotropin [hCG]). 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. Scheduled for surgery during the study, other than minor surgery which would not delay study treatment.

Females of childbearing potential who within 28 days before study entry, did not use a highly effective method of contraception (outlined in protocol)

Males who have not had a successful vasectomy (confirmed azoospermia) or they and their female partners do not meet the criteria above (that is, 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.

Any history of non-infectious pneumonitis or current pneumonitis.

Currently has active, or a history of, interstitial lung disease (ILD).

Has a known history of active TB (bacillus tuberculosis).

Scheduled for surgery during the study, other than minor surgery which would not delay study treatment.

Has an active infection requiring systemic therapy within 4 weeks prior to the first dose of study drug.

Other exclusions apply

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