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

• ClinicalTrials.gov Identifier: NCT04045496
• Recruitment Status: Recruiting
• First Posted: August 5, 2019
• Last Update Posted: October 1, 2019
• Sponsor: Jacobio Pharmaceuticals Co., Ltd.
• Information provided by (Responsible Party): Jacobio Pharmaceuticals Co., Ltd.

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Non-small Cell Lung Cancer; Colorectal Cancer; Pancreatic Ductal Carcinoma; Esophageal Squamous Cell Carcinoma; Head and Neck Squamous Cell Carcinoma; Breast Cancer; Other Solid Tumors	Drug: JAB-3312	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 24 participants
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: September 26, 2019
• Estimated Primary Completion Date: March 2021
• Estimated Study Completion Date: August 2021

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures :

1. Number of participants with dose limiting toxicities [ Time Frame: Approximately 2 years ]
   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.
2. Find Recommended Phase 2 Dose (RP2D) of JAB-3312 [ Time Frame: Approximately 2 years ]
   Measurements of MTD (i.e. the highest dose of JAB-3068 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)

Secondary Outcome Measures :

1. Number of participants with adverse events [ Time Frame: Approximately 2 years ]
   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
2. Area under the curve [ Time Frame: Approximately 2 years ]
   Area under the plasma concentration time curve of JAB-3312
3. Cmax [ Time Frame: Approximately 2 years ]
   Highest observed plasma concentration of JAB-3312
4. Tmax [ Time Frame: Approximately 2 years ]
   Time of highest observed plasma concentration of JAB-3312
5. T1/2 [ Time Frame: Approximately 2 years ]
   Half life of JAB-3312
6. Objective response rate ( ORR ) [ Time Frame: Approximately 2 years ]
   ORR is defined as the proportion of participants with complete response or partial response (CR+PR)
7. Duration of response ( DOR ) [ Time Frame: Approximately 2 years ]
   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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Contacts

Contact: Jacobio Pharmaceuticals; 86 10 56315466; clinicaltrials@jacobiopharma.com

Locations

United States, Colorado

HealthONE Clinic Services Oncology-Hematology; Recruiting

Denver, Colorado, United States, 80202

Contact: Shiraj Sen, MD

United States, Tennessee

Tennessee Oncology, PLLC; Recruiting

Nashville, Tennessee, United States, 37203

Contact: Meredith McKean, MD

United States, Texas

The University of Texas M. D. Anderson Cancer Center; Not yet recruiting

Houston, Texas, United States, 77030

Contact: Sarina A. Piha-Paul, MD

Sponsors and Collaborators

Jacobio Pharmaceuticals Co., Ltd.

Investigators

• Study Director: Jacobio Pharmaceuticals; Jacobio Pharmaceuticals

More Information

• Responsible Party: Jacobio Pharmaceuticals Co., Ltd.
• ClinicalTrials.gov Identifier: NCT04045496 History of Changes
• Other Study ID Numbers: JAB-3312-1001
• First Posted: August 5, 2019
• Last Update Posted: October 1, 2019
• Last Verified: September 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Jacobio Pharmaceuticals Co., Ltd.:

Src homology phosphatase 2 (SHP2); PTPN11; Kirsten rat sarcoma (KRAS) proto-oncogene, GTPase; epidermal growth factor receptor (EGFR)

Additional relevant MeSH terms:

Carcinoma; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck; Esophageal Squamous Cell Carcinoma; Carcinoma, Ductal; Carcinoma, Pancreatic Ductal; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Neoplasms, Squamous Cell; Head and Neck Neoplasms; Esophageal Neoplasms; Esophageal Diseases; Adenocarcinoma; Neoplasms, Ductal, Lobular, and Medullary; Pancreatic Neoplasms; Endocrine Gland Neoplasms; Pancreatic Diseases; Endocrine System Diseases