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

Phase 1

Terminated

• Conditions: Locally Advanced Solid Tumor
• Interventions: Drug: OBI-999

• Registration Number: NCT04084366
• Lead Sponsor: OBI Pharma, Inc

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2019-09-05
• Study First Submitted QC: 2019-09-09
• Study First Posted: 2019-09-10
• Study Start: 2019-11-25
• Primary Completion: 2023-10-27
• Study Completion: 2023-10-27
• Results First Submitted: 2025-02-05
• Status Verified: 2025-03
• Results First Submitted QC: 2025-03-25
• Last Update Submitted: 2025-03-25
• Results First Posted: 2025-03-26
• Last Update Posted: 2025-03-26

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 44

Inclusion Criteria

1. Male or female patients, 18 years of age or older at the time of consent.

2. Provide written informed consent prior to performing any study related procedure.

3. Histologically or cytologically confirmed patients with advanced solid tumors.

4. 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.

5. Measurable disease (i.e., at least one measurable lesion per RECIST 1.1)

6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

7. 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

8. 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.

9. 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.

10. Cannot be breast feeding.

11. 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.

12. 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.

13. 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.

14. 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

1. 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.
2. 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.
3. Sensory or motor neuropathy of Grade 2 or greater.
4. Patients with a history of solid organ transplant.
5. 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.
6. Receipt of any prior therapy targeting Globo H.
7. Known hypersensitivity to OBI 999 or its excipients.
8. 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.
9. Has significant clinical cardiac abnormality (e.g., clinical heart failure or unstable angina)
10. 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.
11. Is receiving any concurrent prohibited medication

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
OBI-999 Expansion Phase	OBI-999	Part B: Five cohorts of patients at RP2D of OBI-999 liquid form, as determined from Part A, via IV infusion.
OBI-999 Escalation phase	OBI-999	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).

Primary Outcome Measures

Name	Time	Method
Objective Response Rate (ORR) (CR+PR)	Every 6 weeks (±7 days) for first 3 months, then every 9 weeks (±7 days) until discontinuation of study treatment, disease progression, death, or initiation of further cancer therapy, or for up to 35 cycles (approximately 2 years.), whichever occurs first	Assessment of OBI-999 clinical benefit rate for dose escalation and cohort expansion phases of the OBI 999-001 study.

Trial Locations

Locations (4)

Memorial Sloan Kettering Cancer Center; 🇺🇸 New York, New York, United States

Scripps MD Anderson Cancer Center; 🇺🇸 La Jolla, California, United States

University of Texas MD Anderson Cancer Center; 🇺🇸 Houston, Texas, United States

West Cancer Center; 🇺🇸 Germantown, Tennessee, United States