Advanced Solid Tumor
Conditions
Brief summary
This is a first-in-human, multicenter, open-label, single-arm, dose-escalation Phase 1 study evaluating the safety, tolerability, pharmacokinetics, pharmacodynamics, immunogenicity, and preliminary antitumor activity of D3L-002 monotherapy in subjects with advanced solid tumors. D3L-002 will be administered as an intravenous infusion every 3 weeks (Q3W) in 21-day cycles. Approximately 24 subjects will be enrolled. Dose escalation will follow a Bayesian Optimal Interval (BOIN) design to determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D).
Interventions
DRUGD3L-002
D3L-002 is an investigational anti-TIGIT/anti-PVRIG bispecific antibody administered as an intravenous infusion every 3 weeks (Q3W).
Sponsors
D3 Bio (Wuxi) Co., Ltd
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Ability to provide written informed consent and comply with study procedures 2. Age ≥18 years 3. Histologically confirmed metastatic or locally advanced incurable solid tumor that has progressed after ≥1 line of therapy or has no available standard treatment 4. Eastern Cooperative Oncology Group (ECOG) performance status 0-1 5. Adequate organ function (hematologic, hepatic, renal) 6. Life expectancy ≥12 weeks 7. Willingness to provide tumor tissue (if available) and blood samples 8. Agreement to use effective contraception 9. Negative pregnancy test for participants of childbearing potential
Exclusion criteria
1. Prior anti-TIGIT or anti-PVRIG therapy 2. Recent anticancer therapy without adequate washout 3. Active or uncontrolled illness 4. Interstitial lung disease/pneumonitis 5. Active Central Nervous System (CNS) disease 6. Uncontrolled effusions 7. Unresolved ≥Grade 2 toxicities 8. Severe prior immunotherapy-related toxicity 9. Active autoimmune disease 10. Active infection 11. Active hepatitis B/C or HIV 12. Recent malignancy (exceptions apply) 13. Significant cardiovascular disease 14. Immunosuppressive therapy within 14 days 15. Live vaccine within 30 days 16. Pregnancy or breastfeeding 17. Hypersensitivity to study drug 18. Investigator-determined unsuitability
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence and Severity of Treatment-Emergent Adverse Events (TEAEs) and Treatment-Related Adverse Events (TRAEs) | From first dose through 30 days after the last dose (Safety Follow-up Visit) | Incidence, nature, and severity of TEAEs and TRAEs assessed and graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 5.0 |
| Change from Baseline in Hemoglobin | From baseline through 30 days after the last dose | Change from baseline in hemoglobin (g/dL) |
| Change from Baseline in White Blood Cell Count | From baseline through 30 days after the last dose | Change from baseline in white blood cell count (×10\^9/L) |
| Change from Baseline in Platelet Count | From baseline through 30 days after the last dose | Change from baseline in platelet count (×10\^9/L) |
| Change from Baseline in Alanine Aminotransferase (ALT) | From baseline through 30 days after the last dose | Change from baseline in alanine aminotransferase (ALT, U/L) |
| Change from Baseline in Aspartate Aminotransferase (AST) | From baseline through 30 days after the last dose | Change from baseline in aspartate aminotransferase (AST, U/L) |
| Change from Baseline in Creatinine | From baseline through 30 days after the last dose | Change from baseline in creatinine (mg/dL) |
| Change from Baseline in Urine Protein | From baseline through 30 days after the last dose | Change from baseline in urine protein (semi-quantitative or mg/dL per local laboratory standard) |
| Change from Baseline in Urine Glucose | From baseline through 30 days after the last dose | Change from baseline in urine glucose (semi-quantitative per local laboratory standard) |
| Change from Baseline in Urine Blood | From baseline through 30 days after the last dose | Change from baseline in urine blood (semi-quantitative per local laboratory standard) |
| Change from Baseline in Systolic Blood Pressure | From baseline through 30 days after the last dose | Change from baseline in systolic blood pressure (mmHg) |
| Change from Baseline in Diastolic Blood Pressure | From baseline through 30 days after the last dose | Change from baseline in diastolic blood pressure (mmHg) |
| Change from Baseline in Heart Rate | From baseline through 30 days after the last dose | Change from baseline in heart rate (beats per minute) |
| Change from Baseline in Respiratory Rate | From baseline through 30 days after the last dose | Change from baseline in respiratory rate (breaths per minute) |
| Change from Baseline in Body Temperature | From baseline through 30 days after the last dose | Change from baseline in body temperature (°C or °F). |
| Change from Baseline in Physical Examination Findings | From baseline through 30 days after the last dose | Evaluation of clinically significant changes from baseline in physical examination findings across body systems (e.g., cardiovascular, respiratory, neurological), as assessed by the investigator and categorized as normal or abnormal. |
| Change from Baseline in Electrocardiogram (ECG) Parameters (QT Interval, PR Interval, QRS Duration, Heart Rate) | From baseline through 30 days after the last dose | Evaluation of clinically significant changes from baseline in 12 lead electrocardiogram (ECG) parameters, including QT interval (milliseconds), PR interval (milliseconds), QRS duration (milliseconds), and heart rate (beats per minute). |
| Determination of Maximum Tolerated Dose (MTD) | Cycle 1 (Day 1 through Day 21) | Determination of MTD based on dose-limiting toxicities (DLTs) occurring during the first cycle (21 days); MTD defined as the dose with estimated DLT rate closest to 30% using a BOIN design |
| Determination of Recommended Phase 2 Dose (RP2D) | Through end of dose-escalation phase (approximately up to 3 months following last subject's first dose) | Determination of RP2D based on the totality of safety, tolerability, pharmacokinetic, pharmacodynamic, and preliminary efficacy data |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics: Maximum Plasma Concentration (Cmax) | From Day 1 through End of Treatment (up to approximately 6 months) | Maximum observed serum concentration of D3L-002 following intravenous administration |
| Pharmacokinetics: Minimum (Trough) Concentration (Ctrough) | From Day 1 through End of Treatment (up to approximately 6 months) | Predose serum concentration of D3L-002 at steady state |
| Pharmacokinetics: Time to Maximum Concentration (Tmax) | From Day 1 through End of Treatment (up to approximately 6 months) | Time from dosing to maximum observed serum concentration of D3L-002 |
| Pharmacokinetics: Terminal Half-Life (t½) | From Day 1 through End of Treatment (up to approximately 6 months) | Terminal elimination half-life of D3L-002 calculated from serum concentration-time data |
| Pharmacokinetics: Area Under the Concentration-Time Curve (AUC) | From Day 1 through End of Treatment (up to approximately 6 months) | Area under the serum concentration-time curve of D3L-002 |
| Immunogenicity: Incidence of Anti-Drug Antibodies (ADA) | From baseline through Safety Follow-up Visit (up to 30 days after last dose) | Incidence of subjects with detectable anti-drug antibodies to D3L-002 |
| Objective Response Rate (ORR) | From first dose through disease progression or end of study (up to approximately 12 months) | Proportion of subjects achieving confirmed complete response (CR) or partial response (PR) per RECIST version 1.1 as assessed by investigators |
| Duration of Response (DOR) | From first documented response until disease progression or death (up to approximately 12 months) | Time from first documented objective response (CR or PR) to disease progression or death |
| Disease Control Rate (DCR) | From first dose through disease assessment period (up to approximately 6 months) | Proportion of subjects achieving CR, PR, or stable disease (SD) lasting at least 6 weeks per RECIST v1.1 |
| Progression-Free Survival (PFS) | From first dose until disease progression or death (up to approximately 12 months) | Time from first dose of D3L-002 to disease progression per RECIST v1.1 or death from any cause |
Countries
Australia, South Korea
Contacts
CONTACTMedical Director
Outcome results
None listed