Phase 1/2 Study of OBI-999 in Patients With Advanced Solid Tumors

Study Overview
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Brief Summary
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The purpose of this study is to establish the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of OBI-999 as monotherapy, and to characterize the safety and preliminary clinical activity profile of the RP2D of OBI-999 in patients with advanced solid tumors.

Official Title
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A Phase 1/2, Open-Label, Dose-Escalation and Cohort-Expansion Study Evaluating the Safety, Pharmacokinetics, and Therapeutic Activity of OBI-999 in Patients With Advanced Solid Tumors

Conditions
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Locally Advanced Solid Tumor

Intervention / Treatment
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* Drug: OBI-999
* Drug: OBI-999


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female patients, 18 years of age or older at the time of consent. Provide written informed consent prior to performing any study related procedure. Histologically or cytologically confirmed patients with advanced solid tumors. Patients must have been treated with established standard-of-care therapy, or physicians have determined that such established therapy is not sufficiently efficacious, or patients have declined to receive standard-of-care therapy. In the latter case, the informed consent must state the effective therapies the patient is declining. Measurable disease (i.e., at least one measurable lesion per RECIST 1.1) Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 Adequate organ function defined as: a. Hepatic: i. Serum ALT ≤3 × upper limit of normal (ULN), ≤5 × ULN in the presence of liver metastases ii. Serum AST ≤3 × ULN, ≤5 × ULN in presence of liver metastases iii.Serum bilirubin ≤1.5 × ULN (unless due to Gilbert's syndrome or hemolysis) b. Renal: i. Creatinine clearance >50 mL/minute using Cockcroft Gault equation c. Hematologic: i. Absolute neutrophil count ≥1,500/µL ii. Platelets ≥100,000/µL iii. Hemoglobin ≥8 g/dL Patient is willing and able to comply with all protocol required assessments, visits, and procedures, including a pretreatment tumor biopsy. Archival tumor biopsies are acceptable at baseline. Females of childbearing potential must have negative serum pregnancy test prior to starting study therapy, and agree to use a reliable form of contraceptive during the study treatment period and for at least 120 days following the last dose of study drug. Patient not of childbearing potential (i.e., permanently sterilized, postmenopausal) can be included in study. Postmenopausal is defined as 12 months with no menses without an alternative medical cause. Male patients must agree to use an adequate method of contraception during the study treatment period and for at least 120 days following the last dose of study drug. Cannot be breast feeding. Patients with human immunodeficiency virus (HIV) infection are eligible if CD4+ T cell counts ≥ 350 cells/uL; patients on antiretroviral therapy (ART) should be on an established dose for at least 4 weeks and have an HIV viral load less than 400 copies/mL prior to enrollment. Patients with serological evidence of chronic hepatitis B virus (HBV) infection are eligible if they have an HBV viral load below the limit of quantification with or without concurrent viral suppressive therapy. Patients with a history of hepatitis C virus (HCV) infection should have completed curative antiviral treatment and have a viral load below the limit of quantification. Patients in Part B (Cohort-Expansion) must have documented Globo H H score of at least 100 from a qualified laboratory IHC assay in one of the sponsor-selected tumor types to be enrolled in the respective cohort: Cohort 1: Pancreatic cancer Cohort 2: Esophageal cancer Cohort 3: Gastric cancer Cohort 4: Colorectal cancer Cohort 5: Basket (any solid tumor type other than those included in Cohorts 1 through 4). Exclusion Criteria: Less than 3 weeks from prior cytotoxic chemotherapy or radiation therapy; and less than 5 half-lives or 3 weeks, whichever is shorter, from prior biologic therapies, prior to the first dose of OBI 999. Has undergone a major surgical procedure (as defined by the Investigator) or significant traumatic injury within 28 days prior to the first dose of OBI 999. Sensory or motor neuropathy of Grade 2 or greater. Patients with a history of solid organ transplant. Unresolved toxicities from prior anticancer therapy, defined as having not resolved to Grade 0 or 1 (using NCI CTCAE version 5.0), except for alopecia and laboratory values listed in the inclusion criteria. Receipt of any prior therapy targeting Globo H. Known hypersensitivity to OBI 999 or its excipients. Has known untreated central nervous system metastases. Patients with treated brain metastases are eligible if there is no evidence of progression for at least 4 weeks after CNS-directed treatment, as ascertained by clinical examination and brain imaging (magnetic resonance imaging [MRI] or computed tomography [CT]) during the screening period. Has significant clinical cardiac abnormality (e.g., clinical heart failure or unstable angina) Any medical co morbidity that is life threatening or, in the opinion of the Investigator, renders the patient unsuitable for participation in a clinical trial due to possible noncompliance, would place the patient at an unacceptable risk and/or potential to affect interpretation of results of the study. Is receiving any concurrent prohibited medication

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: OBI-999 Escalation phase<br>Part A: Five cohorts at escalating dose levels 0.4, 0.8, 1.2, 1.6 and 2.0 mg/kg (capping calculations at a maximum at 100 kg) of OBI-999 liquid form via IV infusion to establish maximum tolerated dose (MTD) and Recommended phase 2 dose (RP2D). | Drug: OBI-999<br>* For the dose-escalation phase, OBI-999 will be administered on Day 1 of each 21-day cycle, for up to 35 cycles.<br>|
| Experimental: OBI-999 Expansion Phase<br>Part B: Five cohorts of patients at RP2D of OBI-999 liquid form, as determined from Part A, via IV infusion. | Drug: OBI-999<br>* For the dose-expansion phase, OBI-999 will be administered on Day 1 of each 21-day cycle, for up to 35 cycles.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measurement of dose-limiting toxicities (DLTs) | Percentage of patients with dose-limiting toxicities (DLTs) observed | First 21 days of each dose escalation cohort | 
| Identification of a maximum tolerated dose and recommended phase 2 dose for OBI-999 | Percentage of patients with adverse events/serious adverse events and laboratory abnormalities as graded by NCI CTCAE version 5.0 | Week 1 to Week 106 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measurement of preliminary clinical activity profile (objective response rate [ORR]) of OBI-999 in patients. | Percentage of patients with ORR per Response Evaluation Criteria in Solid Tumors (RECIST 1.1) | Week 1 to Week 106 | 
| Measurement of preliminary clinical activity profile (clinical benefit rate [CBR]) of OBI-999 in patients. | Percentage of patients with CBR per Response Evaluation Criteria in Solid Tumors (RECIST 1.1) | Week 1 to Week 106 | 
| Measurement of preliminary clinical activity profile (duration of response (DOR)]) of OBI-999 in patients. | Percentage of patients with duration of response (DOR) per Response Evaluation Criteria in Solid Tumors (RECIST 1.1) | Week 1 to Week 106 | 
| Measurement of preliminary clinical activity profile (progression-free survival [PFS]) of OBI-999 in patients. | Percentage of patients with PFS per Response Evaluation Criteria in Solid Tumors (RECIST 1.1) | Week 1 to Week 106 | 
| Measurement of OBI-999 immunogenicity (anti-drug antibodies ([ADAs]) in patients | Percentage of patients with anti-OBI-999 antibodies in blood. | Week 1 to Week 106 | 
| Pharmacokinetics (PK) of OBI-999 and its active metabolite (MMAE) - Cmax | PK parameters will be calculated using a non-compartmental method from the PK samples collected during Cycles 1 and 2 | Week 1 to Week 106 | 
| Pharmacokinetics (PK) of OBI-999 and its active metabolite (MMAE) - total exposure (area under curve, [AUC]) | PK parameters will be calculated using a non-compartmental method from the PK samples collected during Cycles 1 and 2 | Week 1 to Week 106 | 
| Pharmacokinetics (PK) of OBI-999 and its active metabolite (MMAE) - elimination half-life (t1/2) | PK parameters will be calculated using a non-compartmental method from the PK samples collected during Cycles 1 and 2 | Week 1 to Week 106 | 
| Pharmacokinetics (PK) of OBI-999 and its active metabolite (MMAE) - clearance (C1) | PK parameters will be calculated using a non-compartmental method from the PK samples collected during Cycles 1 and 2 | Week 1 to Week 106 | 
| Pharmacokinetics (PK) of OBI-999 and its active metabolite (MMAE) - time to reach maximum concentration (Tmax) | PK parameters will be calculated using a non-compartmental method from the PK samples collected during Cycles 1 and 2 | Week 1 to Week 106 | 
| Pharmacokinetics (PK) of OBI-999 and its active metabolite (MMAE) - volume of distribution (Vd) | PK parameters will be calculated using a non-compartmental method from the PK samples collected during Cycles 1 and 2 | Week 1 to Week 106 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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antibody drug conjugate (ADC)