The primary objective of this study is to evaluate the tolerability and safety profile of MORAb-202 in participants with solid tumors.
Name: MORAb-202
Description: The following toxicities developed in Cycle 1 and causal relationship with MORAb-202 cannot be ruled out are regarded as DLTs: 1) febrile neutropenia; 2)Grade 4 neutropenia that persists for more than 7 days or that requires hematopoietic-stimulating agents; 3)Grade 4 thrombocytopenia, or thrombocytopenia that requires platelet transfusion; 4)Grade 4 anemia or anemia that requires blood transfusion; 5)any Grade 3 non-hematological toxicity with the exception of: a)abnormal clinical laboratory values with no clinical significance; b)any events that can be managed and controlled to Grade 2 or less by maximal medical management; c)infusion reactions of Grade 3 or higher are not considered DLTs because they are stochastic and idiosyncratic events, not related to dose; 6)any Grade 4 non-hematologic toxicity; 7)development of any toxicity that is considered to be related to MORAb-202 and where dose at Cycle 2 Day 1 is necessary to postpone for over 14 days for recovery from the toxicities.
Measure: Part 1: Number of participants with dose-limiting toxicities (DLTs) Time: At the end of Cycle 1 (21 days)Description: Clinical significance will be determined by the Investigator.
Measure: Number of participants with any clinically significant clinical laboratory test value Time: Up to 50 monthsDescription: Clinical significance will be determined by the Investigator.
Measure: Number of participants with any clinically significant vital sign value Time: Up to 50 monthsDescription: Clinical significance will be determined by the Investigator.
Measure: Number of participants with any clinically significant 12-lead electrocardiogram (ECG) value Time: Up to 50 monthsDescription: The MTD will be selected as the dose with the smallest difference between the target DLT rate of 25% and an estimate of DLT rate based on the posterior distribution of DLT rate for each dose.
Measure: Part 1: Maximum Tolerated Dose (MTD) of MORAb-202 Time: 21 days following each dose level of MORAb-202 (up to a maximum of 50 months)Description: Cmax is the maximum serum concentration of MORAb-202 after administration of the drug.
Measure: Part 1 and Part 2: Maximum observed serum concentration (Cmax) of MORAb-202 Time: Predose; end of infusion; 0.5, 1, 2, 4, and 24 hours post infusion on Day 1; on Days 4, 8, and 15; and the discontinuation and last observation visit (up to 50 months)Description: The RD will be determined based on the MTD, efficacy, and safety data in Part 1 and Part 2.
Measure: Recommended dose (RD) of MORAb-202 for future studies Time: From the date of screening until the last observation visit (up to 50 months)Description: BOR was based on Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1). BORs are complete response (CR), partial response (PR), stable disease (SD), progression of disease (PD), and not evaluable (NE), where SD has to be achieved at ≥5 weeks after the first dose. CR or PR in Part 1 of this study requires no confirmation of the next response at ≥4 weeks. CR or PR in Part 2 of this study requires confirmation of the next response at ≥4 weeks.
Measure: Part 1 and Part 2: Best overall response (BOR) Time: From the date of screening until the last observation visit (up to 50 months)Description: ORR is defined as the percentage of participants with BOR of CR or PR.
Measure: Part 1 and Part 2: Overall response rate (ORR) Time: From the date of screening until the last observation visit (up to 50 months)Description: DCR is defined as the percentage of participants with BOR of CR, PR, or SD.
Measure: Part 1 and Part 2: Disease control rate (DCR) Time: From the date of screening until the last observation visit (up to 50 months)Description: CBR is defined as the percentage of participants with BOR of CR, PR or durable (SD) (duration of SD ≥ 23 weeks).
Measure: Part 1 and Part 2: Clinical benefit rate (CBR) Time: From the date of screening until the last observation visit (up to 50 months)Description: DOR is defined as the time from the first documentation of CR or PR to the first documented date of event (disease progression or death from any cause, whichever occurs first).
Measure: Part 2: Duration of Response (DOR) Time: From the date of screening until the last observation visit (up to 50 months)Description: PFS is defined as the time from the date of the first dose of study drug to the first documented date of event (disease progression or death from any cause, whichever occurs first).
Measure: Part 2: Progression-free survival (PFS) Time: From the date of screening until disease progression or death (up to 50 months)Description: OS is defined as the time from the date of the first dose to the date of death from any cause. For participants who are alive or unknown, OS is censored as the date of the last known alive date or the date of data cut off, whichever comes first.
Measure: Part 2: Overall Survival (OS) Time: From the date of screening until the last observation visit (up to 50 months)Allocation: N/A
Single Group Assignment
There is one SNP
- Cohort 1: High grade serous adenocarcinoma - Cohort 2: Other histological types of ovarian carcinoma (excluding mucinous adenocarcinoma) - Cohort 3: NSCLC adenocarcinoma - Cohort 4: NSCLC non-adenocarcinoma - Participants with the following disease characteristics: 1. Ovarian carcinoma (including primary peritoneal carcinoma and fallopian tube carcinoma): - Participants with platinum-resistant disease (defined as progression radiographically within less than [<] 6 months from completion of last platinum therapy) who have received >4 cycles in last platinum-containing chemotherapy for ovarian carcinoma - Participants who have received up to two regimen of chemotherapy after diagnosed as platinum-resistant 2. NSCLC: - Participants that have advanced after previous treatment and those for which no alternative standard therapy exist and those who are not indicated for epidermal growth factor receptor (EGFR), BRAF V600E mutation, anaplastic lymphoma kinase (ALK) or reactive oxygen species (ROS)-targeted therapy (Participants who have progressed after prior such therapy may be eligible) Exclusion Criteria: - Medical history of clinically significant cardiovascular impairment: 1. Congestive heart failure greater than or equal to New York Heart Association Class III. 2. Unstable angina pectoris, myocardial infarction or stroke within 6 months before of the first administration of the study drug. --- V600E ---