A First-in-Human, Phase 1 Study of JAB-3312 in Adult Patients With Advanced Solid Tumors

A Phase 1, Multi-Center, Open-Label Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Evidence of Antitumor Activity of JAB-3312 in Adult Patients With Advanced Solid Tumors

This is a Phase 1, first-in-human, open-label dose-escalation study to determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) and assess the DLT of JAB-3312. It is anticipated that approximately 24 subjects will be enrolled in the dose-escalation phase of the study. JAB-3312 will be administered orally once daily (QD) in 21-day treatment cycles.

Study Overview

• Status: Recruiting
• Conditions: Breast Cancer; Colorectal Cancer; Non-small Cell Lung Cancer; Head and Neck Squamous Cell Carcinoma; Esophageal Squamous Cell Carcinoma; Other Solid Tumors; Pancreatic Ductal Carcinoma
• Intervention / Treatment: Drug: JAB-3312

• Study Type: Interventional
• Enrollment (Anticipated): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Denver, Colorado, United States, 80202
      • Recruiting
      • HealthONE Clinic Services Oncology-Hematology
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Recruiting
      • Tennessee Oncology, PLLC
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • The University of Texas M. D. Anderson Cancer Center
  • Washington
    • Seattle, Washington, United States, 63110
      • Recruiting
      • Washington University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Subject must be ≥18 years-of-age at the time of signature of the informed consent form (ICF).
2. Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1.
3. Subjects with histologically or cytologically confirmed advanced solid tumors which have progressed despite standard therapy or for which no standard therapy exists.
4. Subjects with life expectancy ≥3 months.
5. Patients must have at least one measurable lesion as defined by RECIST v1.1.
6. Patients who have sufficient baseline organ function.

Exclusion Criteria:

1. Severe autoimmune disease (including immune-related adverse events of prior immune-oncology therapy) or autoimmune disorder that requires chronic systemic corticosteroid treatment at immunosuppressive doses (prednisone >10 mg/day or equivalent).
2. Known malignant central nervous system disease other than neurologically stable, treated brain metastases.
3. History or evidence of interstitial lung disease, radiation pneumonitis which required steroid treatment, or idiopathic pulmonary fibrosis, pleural or pericardial effusion that required intervention such as a drain.
4. 8. History of seropositive status for hepatitis B, hepatitis C and human immunodeficiency virus (HIV).
5. History or evidence of active infections (Grade ≥2).
6. History or evidence of significant inflammatory or vascular eye disorder.
7. History of an allogeneic bone marrow or solid organ transplant.
8. Use of systemic anti-cancer agent (except for anti-androgen therapy for prostate cancer) or investigational drug ≤28 days prior to the first dose of JAB-3312.
9. History of radiation therapy ≤28 days prior to the first dose of JAB-3312, or likely to require radiation therapy at any time until the 30 days after the last dose of JAB-3312.
10. History of transfusion of whole blood, red blood cell or platelet packets ≤2 weeks before the start of treatment.
11. Subjects experiencing unresolved Grade >1 toxicity before the start of treatment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: JAB-3312; JAB-3312 will be administered orally once daily in 21 days treatment cycles.	Drug: JAB-3312; JAB-3312 will be supplied as 0.25 mg and 1.0 mg capsules.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with dose limiting toxicities	Incidence of dose limiting toxicities (DLTs) in the dose escalation phase. A DLT is defined as an adverse event or abnormal laboratory value assessed as unrelated to disease, disease progression, inter-current illness, or concomitant medications that occurs within the first treatment cycle with JAB-3312.	Approximately 2 years
Find Recommended Phase 2 Dose (RP2D) of JAB-3312	Measurements of MTD (i.e. the highest dose of JAB-3312 associated with the occurrence of Dose Limiting Toxicities (DLTs) in <33% of patients) or the RP2D (i.e. the highest tested dose that is declared safe and tolerable by the Investigators and Sponsor)	Approximately 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with adverse events	All patients participating in this study will be assessed for incidence and severity of adverse events (AEs) and serious AEs, including changes in laboratory values, vital signs, electrocardiograms, cardiac imaging and ophthalmological assessments	Approximately 2 years
Area under the curve	Area under the plasma concentration time curve of JAB-3312	Approximately 2 years
Cmax	Highest observed plasma concentration of JAB-3312	Approximately 2 years
T1/2	Half life of JAB-3312	Approximately 2 years
Objective response rate ( ORR )	ORR is defined as the proportion of participants with complete response or partial response (CR+PR)	Approximately 2 years
Duration of response ( DOR )	DOR is defined as the time from the participant's initial objective response (CR or PR) to study drug therapy, to disease progression or death due to any cause, whichever occurs first.	Approximately 2 years
Tmax	Time of highest observed plasma concentration of JAB-3312	Approximately 2 years

Collaborators and Investigators

• Sponsor: Jacobio Pharmaceuticals Co., Ltd.

Study record dates

Study Major Dates

• Study Start (ACTUAL): September 26, 2019
• Primary Completion (ANTICIPATED): March 1, 2024
• Study Completion (ANTICIPATED): March 1, 2024

Study Registration Dates

• First Submitted: August 2, 2019
• First Submitted That Met QC Criteria: August 2, 2019
• First Posted (ACTUAL): August 5, 2019

Study Record Updates

• Last Update Posted (ACTUAL): March 15, 2022
• Last Update Submitted That Met QC Criteria: March 13, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: PTPN11; Src homology phosphatase 2 (SHP2); Kirsten rat sarcoma (KRAS) proto-oncogene, GTPase; epidermal growth factor receptor (EGFR)
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Endocrine System Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Endocrine Gland Neoplasms; Head and Neck Neoplasms; Esophageal Diseases; Pancreatic Diseases; Neoplasms, Squamous Cell; Esophageal Neoplasms; Neoplasms, Ductal, Lobular, and Medullary; Pancreatic Neoplasms; Carcinoma; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck; Esophageal Squamous Cell Carcinoma; Carcinoma, Ductal; Carcinoma, Pancreatic Ductal
• Other Study ID Numbers: JAB-3312-1001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No