Advanced Solid Tumor
Conditions
Keywords
TGF-β, thyroid cancer
Brief summary
This is a dose-escalation and dose-expansion Phase 1/2a trial to evaluate the safety and tolerability of DB-1201 in subjects with advanced solid tumors.
Detailed description
This is a multicenter, non-randomized, open-label, multiple-dose, FIH study. The study consists of two parts: Part 1 adopts a rule based 3 + 3 design to identify MTD/RP2D; Part 2 is a dose expansion phase to confirm the safety, tolerability and efficacy in selected solid malignant tumors.
Interventions
DRUGDB-1202
Administered I.V.
Sponsors
DualityBio Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Male or female at least 18 years old. 2. Has histologically or cytologically confirmed metastatic or locally advanced solid tumors for which no effective standard therapy existed or standard of care has failed or is not considered as an option. 3. Is capable of comprehending study procedures and risks outlined in the informed consent and is willing to provide written consent. 4. Has an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0-1. 5. At least one measurable lesion as assessed by the investigator according to response evaluation criteria in solid tumors (RECIST) version 1.1 criteria. 6. Has adequate organ function within 7 days prior to initiation of the first Treatment Cycle 7. Platelet count ≥ 100 000/mm3 8. Hemoglobin (Hb) ≥ 8.5 g/dL 9. Absolute neutrophil count (ANC) ≥ 1500/mm3 10. Creatinine ≤ 1.5 × upper limit of normal (ULN), or 11. Creatinine clearance ≥ 60 mL/min (modification Cockcroft-Gault equation)
Exclusion criteria
1. Has a medical history of symptomatic chronic heart failure (CHF) (New York Heart Association \[NYHA\] classes II-IV) or serious cardiac arrhythmia requiring treatment. 2. Has a medical history of myocardial infarction or unstable angina within 6 months before Day 1. 3. Has a QTc prolongation to \> 470 millisecond (ms) based on a 12-lead electrocardiogram (ECG) in triplicate. 4. Active or prior documented autoimmune disease within the past 2 years. NOTE: Subjects with a history of autoimmune thyroid disease are not excluded. Subjects with vitiligo or psoriasis not requiring systemic treatment (within the past 2 years) are not excluded. 5. Active or prior documented inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis). 6. History of primary immunodeficiency. 7. History of allogeneic organ transplant. 8. Has an uncontrolled infection requiring IV injection of antibiotics, antivirals, or antifungals. 9. Known human immunodeficiency virus (HIV) infection, or active hepatitis B or C infection. 10. Is a lactating mother (women who are willing to temporarily interrupt breastfeeding will also be excluded), or pregnant as confirmed by pregnancy tests performed within 7 days prior to initiation of the first Treatment Cycle. 11. Male and female subjects who are unwilling to use adequate contraceptive methods (double barrier or intrauterine contraceptive) during the study and for at least 7 months after the last dose of study drug.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase 2a: Percentage of Participants with Treatment Emergent adverse events (TEAEs) as assessed by CTCAE v5.0. | Up to follow-up period, approximately 1 year post-treatment | Percentage of participants with AEs in Part 2 graded according to NCI CTCAE v5.0 |
| Phase 1: Percentage of Participants with Treatment Emergent Adverse Events (TEAEs) as assessed by CTCAE v5.0 | Up to follow-up period, approximately 1 year post-treatment | Percentage of participants with AEs in Part 1 graded according to NCI CTCAE v5.0 |
| Phase 1: Percentage of Participants with Serious Adverse Events (SAEs) as assessed by CTCAE v5.0. | Up to follow-up period, approximately 1 year post-treatment | Percentage of Participants with SAEs in Part 1 graded according to NCI CTCAE v5.0 |
| Maximum Tolerated Dose (MTD) of DB-1202 | 12 months | MTD on the data collected during Part 1 |
| Phase 1: Recommended Phase 2 Dose (RP2D) of DB-1202 | 12 months | RP2D of DB-1202 based on the data collected during Part 1 |
| Phase 2a: Percentage participants with Serious Adverse Events (SAEs) as assessed by CTCAE v5.0. | Up to follow-up period, approximately 1 year post-treatment | Percentage of participants with SAEs in Part 2 graded according to NCI CTCAE v5.0 |
| Percentage of Objective Response Rate (ORR) as assessed by RECIST 1.1. | Up to follow-up period, approximately 1 year post-treatment | The percentage of subjects who had a best response rating of CR and PR, for Part 2 only which was maintained ≥4 weeks |
| Phase 1: Percentage of Participants with Dose-Limiting Toxicities (DLTs) as assessed by CTCAE v5.0 | up to 21 days after Cycle 1 Day 1 | Percentage of participants in Part 1 with DLTs |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1 & Phase 2a: Pharmacokinetic-AUC | within 8 cycles (each cycle is 21 days) | Area under the concentration-time curve from time 0 to infinity of DB-1202 |
| Phase 1 & Phase 2a: Pharmacokinetic-Cmax | within 8 cycles (each cycle is 21 days) | Maximum observed plasma concentration (Cmax) of DB-1202 |
| Phase 1 & Phase 2a: Pharmacokinetic-T1/2 | within 8 cycles (each cycle is 21 days) | Terminal elimination half-life |
| Phase 1 & Phase 2a: Pharmacokinetic-Tmax | within 8 cycles (each cycle is 21 days) | Time to Cmax of DB-1202 |
Countries
China
Contacts
Primary ContactJenny Y Li
Backup ContactRen Y Yue
Outcome results
None listed