Clinical trial NCT06959706: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Advanced Solid Tumors
Keywords: Antibody-drug conjugates
Carcinoma
TGW101
TGW101-ADC
TRG001
TAG-72
Cancer
Lead sponsor: Tagworks Pharmaceuticals BV
Sponsor class: INDUSTRY
First posted: 2025-05-06
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: 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 anti-tumor activity.


Eligibility criteria: Inclusion Criteria:

1. Written informed consent prior to any study procedures.
2. Males or females 18 years or older.
3. 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:

   1. Breast cancer (triple negative, estrogen receptor and/or progesterone receptor positive, and/or human epidermal growth factor receptor 2 positive).
   2. Castrate-resistant prostate cancer.
   3. Cervical cancer.
   4. Endometrial cancer.
   5. Esophageal, adenocarcinoma only.
   6. Gastric.
   7. Non-squamous cell carcinoma of the head and neck, e.g., salivary gland neoplasms.
   8. Non-small cell lung cancer, adenocarcinoma only.
   9. Ovarian.
4. 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.
5. At least 1 measurable lesion per RECIST v1.1 except for participants with bone-only metastatic disease.
6. Biopsy pretreatment; if not possible, archival tissue block (preferred) or unstained formalin-fixed paraffin-embedded slides required.
7. Eastern Cooperative Oncology Group Performance Status 0-1.
8. Life expectancy of \> 3 months in the opinion of the Investigator.
9. Adequate hepatic, hematologic, and renal function.

Exclusion Criteria:

1. 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.
2. Known symptomatic brain metastases.
3. Significant cardiovascular disease within 6 months prior to starting study drug.
4. Evidence of an active systemic bacterial, fungal, or viral infection requiring treatment.
5. Grade ≥ 2 peripheral neuropathy.
6. Major surgery within 4 weeks prior to starting study drug.
7. Prior solid organ or bone marrow progenitor cell transplantation.
8. Prior high-dose chemotherapy requiring stem cell rescue.
9. Anticancer therapy within 28 days or within 5 half-lives (whichever is shorter) prior to starting study drug.
10. Palliative radiation therapy within 14 days prior to starting study drug.
11. Live vaccine within 28 days prior to starting study drug.
12. Pregnant or a breastfeeding postpartum female.

Primary outcomes:
measure: Number of Participants Experiencing Adverse Events (AEs)
timeFrame: Up to approximately 10 months
measure: Number of Participants Experiencing Dose Limiting Toxicities (DLTs)
timeFrame: Up to Day 21
measure: Number of Participants Experiencing Cycle Delay
timeFrame: Up to approximately 10 months
measure: Number of Participants Experiencing Dose Reduction
timeFrame: Up to approximately 10 months
measure: RDE of TGW101
timeFrame: Up to approximately 10 months
Secondary outcomes:
measure: Area Under the Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUClast) of TGW101-ADC Related Analytes
timeFrame: Up to approximately 10 months
measure: Area Under the Concentration-time Curve From Time Zero to the end of the Dosing Interval (AUCtau) of TGW101-ADC Related Analytes
timeFrame: Up to approximately 10 months
measure: Area Under the Concentration-time Curve From Time Zero to Infinity (AUCinf) of TGW101-ADC Related Analytes
timeFrame: Up to approximately 10 months
measure: Maximum Concentration (Cmax) of TGW101-ADC Related Analytes
timeFrame: Up to approximately 10 months
measure: Trough Concentration (Ctrough) of TGW101-ADC Related Analytes
timeFrame: Up to approximately 10 months
measure: Time to Maximum Concentration (Tmax) of TGW101-ADC Related Analytes
timeFrame: Up to approximately 10 months
measure: Apparent Terminal Elimination Half-life (t1/2) of TGW101-ADC Related Analytes
timeFrame: Up to approximately 10 months
measure: Steady-state Volume of Distribution (Vss) of TGW101-ADC Related Analytes
timeFrame: Up to approximately 10 months
measure: Clearance (CL) of TGW101-ADC Related Analytes
timeFrame: Up to approximately 10 months
measure: Accumulation Index of TGW101-ADC Related Analytes
timeFrame: Up to approximately 10 months
measure: Overall Response Rate (ORR)
timeFrame: Up to approximately 10 months
measure: Duration of Response (DOR)
timeFrame: Up to approximately 10 months
measure: Progression-free Survival (PFS)
timeFrame: Up to approximately 10 months
measure: Overall Survival (OS)
timeFrame: Up to approximately 10 months
measure: Number of Participants Experiencing Antidrug Antibodies (ADAs) Against TGW101-ADC
timeFrame: Up to approximately 10 months
Other outcomes:
Locations:
city: Irving
country: United States
facility: NEXT Dallas
state: Texas
city: San Antonio
country: United States
facility: NEXT San Antonio
state: Texas
city: Fairfax
country: United States
facility: NEXT Virginia
state: Virginia
Study officials:
References: