The study is a first-in-human (FIH), open-label, multi-center phase 1/2 study of TSN1611 in subjects with KRAS G12D mutant advanced solid tumors. This study will consist of a phase 1 dose escalation part and phase 2 dose expansion part. This study will evaluate the efficacy of TSN1611 at RP2D(s) through ORR using RECIST version 1.1, and determine and confirm the MTD/RP2D for TSN1611 in combination with cetuximab, in combination with cetuximab and mFOLFOX6, in combination with gemcitabine and albumin-bound paclitaxel in subjects with selected solid tumors.
Phase 1 Part of TSN1611 Monotherapy: The phase 1 part will evaluate the prespecified dose levels of TSN1611. Dose escalation will continue until up to the highest planned dose or the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) is determined. Dose optimization could be performed as indicated by the emerging data. Phase 2 Part of TSN1611 Monotherapy: hase 2 part of TSN1611 monotherapy will evaluate the efficacy and safety of TSN1611 as monotherapy at the RP2D until disease progression or unacceptable toxicity in separate groups of patients with pancreatic cancer, colorectal cancer, non-small cell lung cancer, or other solid tumors, harboring KRAS G12D mutations. Phase 1b/2 Part of TSN1611 Combination Therapy: This part will consist of the investigations of 3 combined therapies (Cohort A, B and C). In each cohort, there will be a Phase 1b Safety Lead-in Stage to determine the dose of TSN1611 for the combination therapy (this part will be conducted in selected sites), followed by the Phase 2 Expansion Stage to enroll more subjects to determine the efficacy in different cohorts.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
440
TSN1611 will be administered at the assigned dose level, orally, until disease progression or intolerable toxicity.
TSN1611 BID, Cetuximab will be administered via intravenous infusion at a dose of 500 mg/m² every 2 weeks.
TSN1611 BID, Paclitaxel (albumin-bound) at 125 mg/m² and gemcitabine at 1000 mg/m² will be administered via intravenous infusion on Days 1, 8, and 15 of each 4-week cycle.
TSN1611 BID everyday and Patients will be administered with mFOLFOX6 on Days 1 and 2, every 2 weeks.
MD Anderson Cancer Center
Houston, Texas, United States
RECRUITINGNEXT Oncology
San Antonio, Texas, United States
RECRUITINGNEXT Virginia
Fairfax, Virginia, United States
RECRUITINGAnhui Provincial Cancer Hospital
Hefei, Anhui, China
RECRUITINGBeijing Cancer Hospital
Beijing, Beijing Municipality, China
RECRUITINGThe First Affiliated Hospital of Guangzhou Medical University
Guangzhou, Guangdong, China
RECRUITINGHubei Cancer Hospital
Wuhan, Hubei, China
RECRUITINGHunan Cancer Hospital
Changsha, Hunan, China
RECRUITINGThe First Affiliated Hospital of Nanchang University - Donghu District
Nanchang, Jiang, China
RECRUITINGLinyi Cancer Hospital
Linyi, Shandong, China
RECRUITING...and 9 more locations
Dose limiting toxicities (DLTs) in phase 1 part
To determine the maximum tolerated dose (MTD) and/or recommended phase 2 dose(s) (RP2D\[s\]) of TSN1611 as monotherapy in subjects with KRAS G12D mutant advanced solid tumors.
Time frame: 21 days
Objective response rate (ORR) in phase 2 part
To evaluate the anti-tumor activity of TSN1611 using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
Time frame: Up to 3 years
Adverse events
To assess the safety profile and tolerability of TSN1611 as monotherapy in subjects with KRAS G12D mutant advanced solid tumors.
Time frame: Up to 3 years
Area under the plasma concentration-time curve (AUC)
To characterize the pharmacokinetic (PK) profile of TSN1611.
Time frame: 9 weeks
Maximum blood concentrations (Cmax)
To characterize the PK profile of TSN1611.
Time frame: 9 weeks
Time to maximum blood concentration (Tmax)
To characterize the PK profile of TSN1611.
Time frame: 9 weeks
Duration of response (DOR)
To evaluate the anti-tumor activity of TSN1611 using RECIST version 1.1.
Time frame: Up to 3 years
Time to response (TTR)
To evaluate the anti-tumor activity of TSN1611 using RECIST version 1.1.
Time frame: Up to 3 years
Disease control rate (DCR)
To evaluate the anti-tumor activity of TSN1611 using RECIST version 1.1.
Time frame: Up to 3 years
Progression free survival (PFS)
To evaluate the anti-tumor activity of TSN1611 using RECIST version 1.1.
Time frame: Up to 3 years
Overall survival
Time frame: Up to 3 years
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