A Phase Ib/II Study of GT90001 Combined With KN046 in Solid Tumors

NCT04984668 | Recruiting Phase 1

• 1 other identifier: GT90001-TW-2001
• Study Type: interventional
• Target: 216
• Locations: 1 country
• Sites: 1

Brief Summary

Phase Ib is a dose De-escalation study to evaluate the safety, tolerability, pharmacokinetics (PK) and preliminary antitumor activity of GT90001 in combination with KN046 in subjects with advanced or refractory hepatocellular carcinoma (HCC), gastric carcinoma (GC) and gastroesophageal junction (GEJ) adenocarcinoma, urothelial carcinoma (UC) and esophageal square cell carcinoma (ESCC). Phase II is to investigate anti-tumor efficacy of GT90001 in combination with KN046 at RP2D in subjects with specific types of tumors. A Simon two-stage design is planned for each indication in order to minimize the number of treated participants if there is minimal efficacy activity in that indication.

Conditions

Solid Tumor

Outcome Measures

Primary Outcomes (3)

• Treatment-emergent adverse events (TEAEs), treatment-related AEs (TRAEs), serious adverse events (SAEs), Dose Limiting Toxicities (DLTs)

  safety

  until progression or death,whichever came first, assessed up to 2 years

• Phase 2 dose (RP2D) of GT90001 in combination with KN046

  RP2D

  after completion of the DLT evaluation of the last subject of Phase Ib, up to 28 days

• Objective response rate

  Efficacy

  until progression or death,whichever came first, assessed up to 2 years

Secondary Outcomes (4)

• ORR (Phase Ib) in %, disease control rate (DCR) in %, progression-free survival (PFS)in months, and duration of response (DoR) in %

  until progression or death,whichever came first, assessed up to 2 years

• AUC0-t, Cmax, Tmax, t½ , CLss for GT90001 , Ctroug for KN046 (only Phase Ib)

  until progression or death,whichever came first, assessed up to 2 years

• occurrence of anti-GT90001 and anti-KN046 antibody

  until progression or death,whichever came first, assessed up to 2 years

• TEAEs, severity of TEAEs, TRAEs, SAEs

  until progression or death,whichever came first, assessed up to 2 years

Study Arms (1)

GT90001+KN046

EXPERIMENTAL

GT90001, 100 mg/10 mL/vial. GT90001 will be administered via intravenous infusion (IV) for around 60 minutes, once every 2 weeks (Q2W) in each 14-day cycle. KN046, 40 mg/1.6 mL/vial, 300 mg/12 mL/vial KN046 will be administered via intravenous infusion (IV) for at least 120 minutes (up to 4h for the first 6 cycles), once every 2 weeks (Q2W) in each 14-day cycle, after 60 minutes post the GT90001 taken.

Drug: GT90001+KN046; Drug: GT90001/KN046

Interventions

GT90001+KN046 DRUG

GT90001 7.0mg/Kg， KN046 5mg/Kg

GT90001+KN046

Eligibility Criteria

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

You may qualify if:

• General
• Age ≥18 years, or ≥ minimum legal age to attend a clinical study.
• Be willing and able to provide written informed consent/assent for the trial.
• Ability to comply with requirements of the protocol, as assessed by the investigator.
• Phase Ib: subjects with advanced HCC, GC or GEJ adenocarcinoma, Urothelial transitional cell Carcinoma and Esophagus Carcinoma who have progressed despite standard therapies, are intolerant of standard therapy, or for whom no standard therapy exists;
• Phase II: subjects with tumor of specific types:
• HCC, 2L Unresectable histologic confirmed primary hepatocellular carcinoma. Subjects with radiological diagnosis may also be enrolled in the study.
• Documented radiographic or clinical disease progression during or after 1st line therapy, including Sorafenib, Lenvatinib and Atezolizumab plus Bevacizumab and other 1st line standard care per local clinical practice.
• Patient has a Child-Pugh score of 5 or 6 points and no encephalopathy and/or clinically apparent ascites. (Note: Child-Pugh score should be evaluated within 7 days of first dose of study drug)
• GC or GEJ adenocarcinoma, 3L Unresectable locally advanced or metastatic GC or GEJ carcinoma and have histologically confirmed adenocarcinoma.
• At least 50% subjects with PD-L1 expression (CPS) on ≥ 1% will be enrolled in this cohort.
• Has experienced documented objective radiographic or clinical disease progression during or after standard first line Platinum- and fluoropyrimidine-based two or three cytotoxic drug chemotherapy and second line NCCN recommended treatment regimen therapy or other 1st and 2nd line standard care per local clinical practice. (Note: subjects with discontinuation due to AEs prior to disease progression are not considered as treatment failure unless disease progression is confirmed by documentation.) Disease progression during or within 6 months following the last dose of adjuvant or neo-adjuvant therapy will be considered as 1st line failure.
• UC, 2L Histologically or cytologically confirmed urothelial carcinoma of the renal pelvis, ureter, bladder, or urethra that showed predominantly transitional-cell features Has experienced documented progression or recurrence after at least the 1st line platinum-based chemotherapy or recurrence within 12 months after the receipt of platinum-based adjuvant or neoadjuvant therapy for localized muscle-invasive disease.
• Note: Primary chemoradiation for unresectable muscle-invasive bladder cancer with the aim of bladder preservation will not be considered a prior line of systemic therapy for the purposes of determining study eligibility.
• ESCC 2L Histologically confirmed, unresectable squamous cell carcinoma of the esophagus.

You may not qualify if:

• HCC, 2L Fibrolamellar, sarcomatoid and mixed hepatocellular/ cholangiocarcinoma histology Any history of hepatic encephalopathy Active coinfection with both hepatitis B and C, as evidenced by positivity of both HBV DNA and HCV RNA.
• GC or GEJ adenocarcinoma, 3L Has squamous cell, undifferentiated, mixed or other histology other than gastric adenocarcinoma.
• UC, 2L Has locally advanced UC is suitable for local therapy administration with curative intention (as determined by local investigators)
• ESCC 2L Has locally advanced esophageal carcinoma that is resectable or potentially curable with radiation therapy (as determined by local investigator) Histologically confirmed, unresectable adenocarcinoma, undifferentiated carcinomas or adenosquamous carcinomas of the esophagus.
• Tumors that involve the GE junction Sievert Type 2 and Sievert Type 3, or greater than 50% of the tumor below the GE junction as determined by endoscopy.
• Medical History and Concurrent Diseases
• \. Prior malignancy active within the previous 3 years except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix, or breast.
• Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Patients with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least 4 weeks prior to the first dose of investigational product and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to study treatment.
• Any prior (within 1 year) or current clinically significant ascites as measured by physical examination and that requires active paracentesis for control.
• Patients with active, known, or suspected autoimmune disease. Patients with Type I diabetes mellitus, residual hypothyroidism due to autoimmune thyroiditis only requiring hormone replacement, or skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment are permitted to enroll. For any cases of uncertainty, it is recommended to discuss with sponsor prior to signing informed consent.
• Significant history of cardiac disease (i.e., unstable angina, congestive heart failure, as defined by the New York Heart Association \[NYHA\] as Class II, III, or IV) within 6 months prior to Day 1 of Cycle 1, myocardial infarction within the previous year, or current cardiac ventricular arrhythmias requiring medication., or left ventricular ejection fraction (LVEF) is below 50%.
• Arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism within 6 months before the start of study treatment.
• Any hemorrhage or bleeding event≥ CTCAE Grade 3 within 28 days prior to the start of study treatment.
• Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis.
• Patients with active tuberculosis or history of tuberculosis.

Sponsors & Collaborators

• Suzhou Kintor Pharmaceutical Inc,: lead
• Jiangsu Alphamab Biopharmaceuticals Co., Ltd: collaborator

Study Sites (1)

Chi-Mei Medical Center

Tainan, Taiwan

RECRUITING

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: July 5, 2021
• First Posted: July 30, 2021
• Study Start: November 2, 2021
• Primary Completion: April 1, 2025
• Study Completion: December 1, 2025
• Last Updated: February 9, 2024

Record last verified: 2024-02

Locations

TW (1)