Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of TGW101 in Participants With Advanced Solid Tumors

Official title

Phase 1, First-in-Human, Open-Label Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of TGW101 in Patients With Advanced Solid Tumors

Overview

The primary objectives of this study are to evaluate the safety and tolerability of TGW101 and determine the recommended dosing regimen(s) for further study. The secondary objectives are to assess pharmacokinetics and preliminary antitumor activity.

Interventions

• Drug TGW101
  TGW101 is a combination product comprising a chemically cleavable diabody drug conjugate (TGW101-ADC) and a corresponding small molecule chemical trigger (TRG001) administered separately.

Primary outcome measures

• Number of Participants Experiencing Adverse Events (AEs) [Time frame: Up to approximately 10 months]
• Number of Participants Experiencing Dose-limiting Toxicities (DLTs) [Time frame: Up to Day 21]
• Number of Participants Experiencing Cycle Delay [Time frame: Up to approximately 10 months]
• Number of Participants Experiencing Dose Reduction [Time frame: Up to approximately 10 months]
• RDE of TGW101 [Time frame: Up to approximately 10 months]

Secondary outcome measures (12)

• Area Under the Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUClast) of TGW101-ADC and TRG001 [Time frame: Up to approximately 10 months]
• Area Under the Concentration-time Curve From Time Zero to the end of the Dosing Interval (AUCtau) of TGW101-ADC and TRG001 [Time frame: Up to approximately 10 months]
• Area Under the Concentration-time Curve From Time Zero to Infinity (AUCinf) of TGW101-ADC and TRG001 [Time frame: Up to approximately 10 months]
• Maximum Concentration (Cmax) of TGW101-ADC and TRG001 [Time frame: Up to approximately 10 months]
• Trough Concentration (Ctrough) of TGW101-ADC and TRG001 [Time frame: Up to approximately 10 months]
• Time to Maximum Concentration (Tmax) of TGW101-ADC and TRG001 [Time frame: Up to approximately 10 months]
• Apparent Terminal Elimination Half-life (t1/2) of TGW101-ADC and TRG001 [Time frame: Up to approximately 10 months]
• Steady-state Volume of Distribution (Vss) of TGW101-ADC and TRG001 [Time frame: Up to approximately 10 months]
• Clearance (CL) of TGW101-ADC and TRG001 [Time frame: Up to approximately 10 months]
• Accumulation Index of TGW101-ADC and TRG001 [Time frame: Up to approximately 10 months]
• Overall Response Rate (ORR) [Time frame: Up to approximately 10 months]
• Duration of Response (DOR) [Time frame: Up to approximately 10 months]

Eligibility criteria

Inclusion criteria

• Written informed consent prior to any study procedures.
• Males or females 18 years or older.
• Histologically or cytologically confirmed diagnosis of a solid tumor malignancy listed below, with radiographic evidence of disease progression based on Response Evaluation Criteria in Solid Tumors (RECIST v1.1), or for castration resistant prostate cancer (CRPC), Prostate Cancer Clinical Trials Working Group 3, after most recent treatment and locally advanced or metastatic disease at Screening:

• Breast cancer (all subtypes).
• Castrate-resistant prostate cancer.
• Cervical cancer.
• Endometrial cancer.
• Esophageal, adenocarcinoma only.
• Gastric/gastroesophageal junction (GEJ).
• Non-squamous cell carcinoma of the head and neck, e.g., salivary gland neoplasms, with the exception of adenoid cystic carcinoma.
• Non-small cell lung cancer, adenocarcinoma only.
• Ovarian.
• Refractory disease, intolerance to, or documented refusal of available standard therapy(ies) known to provide clinical benefit for the participant's solid tumor malignancy per Investigator judgment.
• At least 1 measurable lesion per RECIST v1.1 except for participants with bone-only metastatic disease.
• Biopsy pretreatment; if not possible, archival tissue block (preferred) or unstained formalin-fixed paraffin-embedded slides required.
• Eastern Cooperative Oncology Group Performance Status 0-1.
• Life expectancy of > 3 months in the opinion of the Investigator.
• Adequate hepatic, hematologic, and renal function.

Exclusion criteria

• Active second malignancy or history of another malignancy within the last 2 years, with the exception of: treated non-melanoma skin cancers; treated carcinoma in situ (e.g., breast and cervix); controlled superficial carcinoma of the urinary bladder; T1a or b carcinoma of the prostate; papillary thyroid carcinoma Stage I treated surgically for cure.
• Known symptomatic brain metastases.
• Significant cardiovascular disease within 6 months prior to starting study drug.
• Evidence of an active systemic bacterial, fungal, or viral infection requiring treatment.
• Grade ≥ 2 peripheral neuropathy.
• Major surgery within 4 weeks prior to starting study drug.
• Prior solid organ or bone marrow progenitor cell transplantation.
• Prior high-dose chemotherapy requiring stem cell rescue.
• Anticancer therapy within 28 days or within 5 half-lives (whichever is shorter) prior to starting study drug.
• Palliative radiation therapy within 14 days prior to starting study drug.
• Live vaccine within 28 days prior to starting study drug.
• Pregnant or a breastfeeding postpartum female.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 7 centers

• Honor Health — Scottsdale
• Massachusetts General Hospital — Boston
• Fox Chase Cancer Center — Philadelphia
• University of Texas MD Anderson Cancer Center — Houston
• NEXT Dallas — Irving
• NEXT San Antonio — San Antonio
• NEXT Virginia — Fairfax

Identifiers

NCT: NCT06959706 · TGW101-101

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗