A Phase 1/2, First-in-Human, Open Label, Dose Escalation Study Of A CSP Targeting Functional Antibody in Solid Tumors

NCT05074472 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: ZIEL-ZB131-101
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 9

Brief Summary

This study is a first-in-human, Phase 1, open label, multicenter, dose escalation study with expansion at the RP2D, to evaluate the safety, tolerability, and preliminary efficacy of ZB131 in patients with solid tumors where prevalence of CSP expression is high. Approximately 12 to 24 patients will be enrolled in the Dose Escalation Stage; the total number of patients will depend on the dose level at which the RP2D is defined. Patients who meet the eligibility criteria during Screening will enter the treatment period. ZB131 will be given via IV every week. Patients will be treated until disease progression or unacceptable toxicities occur.

Conditions

Solid Tumor, Adult; Pancreatic Ductal; Adenocarcinoma; Ovarian Serous Adenocarcinoma; Biliary Cancer Metastatic; Ovarian Serous Cystadenocarcinoma

Keywords

Advanced or Metastatic Ovarian Cancer (ovarian serous adenocarcinoma; ovarian serous cystadenocarcinoma); Advanced or Metastatic Biliary Cancer (intrahepatic, extrahepatic, gallbladder); Advanced or Metastatic Pancreatic Cancer (pancreatic ductal; adenocarcinoma)

Outcome Measures

Primary Outcomes (1)

• Maximum plasma concentration (Cmax)

  Determine maximum plasma concentration (Cmax)

  1 month

Study Arms (1)

Active Treatment: ZB131

EXPERIMENTAL

During the Dose Escalation Stage, patients will be treated with ZB131 at increasing dose levels, beginning with a starting dose level (DL0) of 3 mg/kg once weekly, up to a maximum dose level (DL3) of 15 mg/kg once weekly.

Drug: ZB131

Interventions

ZB131 DRUG

ZB131 will be administered once weekly by intravenous infusion with the weight at baseline used for mg/kg dose calculations.

Active Treatment: ZB131

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female ≥18 years of age at the time of signing informed consent.
• Diagnosis of histologically or cytologically confirmed advanced solid tumors
• Dose Escalation Stage: patients with solid tumors (excluding melanoma and hepatocellular CR) who have failed all available therapies or are not eligible for standard of care (SOC).
• Dose Expansion Stage:
• i. Cohort A: Advanced or Metastatic Pancreatic Cancer (pancreatic ductal; adenocarcinoma) who have failed or are not eligible for SOC; ii. Cohort B: Advanced or Metastatic Ovarian Cancer of the serous type (ovarian serous adenocarcinoma; ovarian serous cystadenocarcinoma) who have failed or are not eligible for SOC; iii. Cohort C: Advanced or Metastatic Biliary Cancer (intrahepatic, extrahepatic, gallbladder) who have failed or are not eligible for SOC.
• Eastern Cooperative Oncology Group (ECOG) status of 0-1.
• Measurable disease per RECIST as assessed by local site investigator/radiologists; lesions situated in previous irradiated areas are considered measurable if progression has been demonstrated in such lesions.
• Patients must have a tumor lesion that can be safely biopsied and agree to provide a fresh or archival tissue sample prior to treatment initiation and agree to an on-treatment biopsy. The on-treatment biopsy may be waived for patients in the Dose Escalation Stage if a biopsy sample is not possible. An archival sample must be ≤6 months old.
• Locally advanced, recurrent, or metastatic neoplastic disease that has failed to respond to standard therapy, is not curable by currently available local therapies, or for whom no appropriate therapies are available (based on the judgement of the Investigator.
• Life expectancy of ≥3 months in the judgement of the Investigator
• Adequate hematologic function based on the following:
• a. Absolute neutrophil count ≥1.5 x 109/L b. Platelet count ≥100 x 109/L c. Hemoglobin ≥9.0 g/dL
• Adequate coagulation parameters based on the following:
• a. Prothrombin Time-International Normalized Ratio/partial thromboplastin time (PT-INR/PTT) \< ) \<1.5 x ULN, unless coumarin derivatives are used; and b. Partial thromboplastin time (PTT) or activated partial thromboplastin time (APTT) \<1.25 x ULN (therapeutic anticoagulation.
• Note: Anti-coagulation therapy is allowed, if this treatment canpermitted but should be able to be interrupted for a biopsy as judgedif deemed necessary by the Investigator).. The coagulation parameters for patients on anti-coagulation will be interpreted according to expected institutional therapeutic parameters.

You may not qualify if:

• Major surgery within 4 weeks prior to Screening. Major surgery is any invasive operative procedure in which a more extensive resection is performed, e.g. a body cavity is entered, organs are removed, or normal anatomy is altered. In general, if a mesenchymal barrier is opened (pleural cavity, peritoneum, meninges), the surgery is considered major. Minimally invasive (laparoscopic) procedures are not considered major surgery, unless considered high risk and requiring extended (greater than over- night observation).
• Prior radiotherapy within 2 weeks of start of study treatment. Patients must have recovered from all radiation-related toxicities, not require corticosteroids for their radiation therapy, and no history of radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-central nervous system disease.
• Anti-cancer therapy, such as chemotherapy, immunotherapy, hormonal therapy, targeted therapy, or investigational agents within five half-lives or four weeks, whichever is shorter, prior to administration of the first dose of study treatment. Hormonal therapy as maintenance when there is no evaluable cancer is allowed.
• Active CNS metastases; however, patients who have undergone radiation and/or surgery for the treatment of CNS metastases, who are neurologically stable, and who are no longer taking pharmacologic doses of corticosteroids are eligible; patients with leptomeningeal metastases are not eligible.
• Primary CNS malignancy.
• Evidence of metastatic ileus on CT.
• Severe gastrointestinal conditions such as clinical or radiological evidence of bowel obstruction within 4 weeks prior to study entry;
• Known active Infection with human immunodeficiency virus (HIV), hepatitis B (HBV), or hepatitis C virus (HCV):
• a. Patients with HIV are excluded.
• a.b. Patients who are hepatitis B surface antigen positive are eligible if they have received hepatitis B virus antiviral therapy for at least 4 weeks and have undetectable HBV viral load prior to enrollment.
• i. Note: Patients should remain on antiviral therapy throughout study intervention and follow local guidelines for HBV antiviral therapy post completion of study intervention.
• ii. Hepatitis B screening tests are not required unless:
• \. Known history of HBV infection, 2. Mandated by local health authority. b.c. Patients with a history of hepatitis C virus infection are eligible if HCV viral load is undetectable at Screening.
• i. Note: Patients must have completed curative antiviral therapy at least 4 weeks prior to enrollment.
• ii. Hepatitis C screening tests are not required unless: 1. Known history of HCV infection, 2. Mandated by local health authority. 9. Requiring immunosuppressive therapy. 10. Ongoing systemic bacterial, fungal, or viral infections at Screening;

Sponsors & Collaborators

• ZielBio, Inc.: lead

Study Sites (9)

Mayo Clinic - Phoenix

Phoenix, Arizona, 85054, United States

Location

Mayo Clinic Jacksonville

Jacksonville, Florida, 32224, United States

Location

Mayo Clinic - Rochester

Rochester, Minnesota, 55905, United States

Location

Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

Location

NEXT Oncology

Austin, Texas, 78758, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

NEXT Oncology

San Antonio, Texas, 78229, United States

Location

University of Virginia

Charlottesville, Virginia, 22908, United States

Location

NEXT Onoology

Fairfax, Virginia, 22031, United States

Location

MeSH Terms

Conditions

Adenocarcinoma; Ovarian Neoplasms; Biliary Tract Neoplasms; Pancreatic Neoplasms

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Endocrine Gland Neoplasms; Neoplasms by Site; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Digestive System Neoplasms; Biliary Tract Diseases; Digestive System Diseases; Pancreatic Diseases

Study Officials

• Ramesh Ramanathan, MD

  ZielBio, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 23, 2021
• First Posted: October 12, 2021
• Study Start: January 14, 2022
• Primary Completion: August 30, 2023
• Study Completion: September 30, 2023
• Last Updated: January 29, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (9)