Clinical trial NCT05976334: An Absorption, Distribution, Metabolism, Excretion (ADME) Study of [14C]Subasumstat in Adults With Advanced or Metastatic Solid Tumors
Official title: A Phase 1 Study to Assess Mass Balance, Pharmacokinetics, and Metabolism of [14C]Subasumstat in Patients With Advanced or Metastatic Solid Tumors
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Solid Tumors
Keywords: Drug Therapy
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2023-08-04
Enrollment: 3
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The main aim of this study is to assess how the human body of adults with advanced or metastatic solid tumors absorbs, distributes, metabolizes and excretes subasumstat following a single 1 hour infusion of subasumstat.

The study consists of two parts. In Part A, participants will receive a single infusion of C14 radiolabeled subasumstat. In Part B, participants will receive subasumstat treatment for up to 1 year.

Detailed description: The drug being tested in this study is called \[14C\]subasumstat. \[14C\]Subasumstat is being tested to assess mass balance and absorption, distribution, metabolism, excretion (ADME) of people who have advanced or metastatic solid tumors.

The study will enroll approximately 10 patients. Participants will be enrolled to receive a single dose of \[14C\]subasumstat:

- \[14C\]Subasumstat 90 mg

Participants will be administered with a single dose of \[14C\]subasumstat 90 mg as a 1-hour intravenous (IV) infusion on Day 1 of Part A. All participants will be monitored for up to 14 days postdose. Participants will then have an option to enter Part B of the study to receive non-radiolabelled subasumstat 90 mg, IV infusion on Days 1, 4, 8, and 11 of a 21-day cycle for 3 cycles up to maximum treatment duration of 1 year.

This multi-center trial will be conducted in Hungary. The overall study duration is 12 months for Part A and 24 months for Part B.

Eligibility criteria: Key Inclusion Criteria:

1. Participants have histologically or cytologically confirmed advanced (locally regionally recurrent not amenable to curative therapy) or metastatic solid tumors with no standard therapeutic option with a proven clinical benefit, are intolerant or have refused them.
2. Participants have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group Performance Scale.
3. Participants demonstrate adequate organ function.
4. Participants have recovered to Grade 1 or baseline from all toxicity associated with previous therapy or have the toxicity established as sequela.

Key Exclusion Criteria:

1. Participants received treatment with radioisotopes within 5 half-lives before the first dose of the study drug.
2. Participants received radiolabelled substances, were exposed to radiation sources within 12 months of the first dose in this study, or is likely to receive radiation exposure or radioisotopes within 12 months of the first dose in this study such that participation in this study would increase their total exposure beyond the recommended safe levels.
3. Participants received extended field radiotherapy ≤4 weeks before the start of treatment.
4. Participants have uncontrolled brain metastasis. Participants with treated brain metastases are allowed provided they are radiologically stable, without evidence of progression for at least 4 weeks by repeat imaging, clinically stable, and without requirement of steroid treatment for at least 14 days before first dose of study treatment.
5. Participants had a second malignancy within the previous 3 years, except treated basal cell or localized squamous skin carcinomas, prostate cancer, cervical carcinoma in situ, resected colorectal adenomatous polyps, breast cancer in situ, or other malignancy for which the patient is not on active anticancer therapies.
6. Major surgery ≤14 days from the first dose of study drug and not recovered fully from any complications from surgery.
7. Baseline prolongation of the QT interval when corrected using Fridericia's formula (QTcF).
8. Receiving or requires the continued use of medications that are known to be strong or moderate inhibitors and inducers of cytochrome P450 (CYP) 3A4/5 and strong P-glycoprotein (Pgp) inhibitors.
9. Has active noninfectious pneumonitis or interstitial lung disease that required steroids.
10. History of allogeneic tissue or solid organ transplant.
11. Participants have active bacterial infection requiring systemic therapy \<14 days before the start of treatment.
12. Participants have an active HIV or any other relevant congenital or acquired immunodeficiency.
13. Active hepatitis B, or hepatitis C infection.
14. Any of the following uncontrolled heart diseases: congestive heart failure New York Heart Association Grade III or IV, unstable angina, myocardial infarction, unstable symptomatic ischemic heart disease, uncontrolled hypertension despite appropriate medical therapy, ongoing symptomatic cardiac arrhythmias \>Grade 2, pulmonary embolism or symptomatic cerebrovascular events, or any other serious cardiac condition (eg, pericardial effusion or restrictive cardiomyopathy). Chronic atrial fibrillation on stable anticoagulant therapy is allowed.

Primary outcomes:
measure: Cumulative Percentage of Urinary Recovery
timeFrame: Up to 14 days postdose
measure: Cumulative Percentage of Fecal Recovery
timeFrame: Up to 14 days postdose
measure: Cumulative Percentage of Combined Recovery
timeFrame: Up to 14 days postdose
measure: Percentage Of Recovered Total Radioactivity (TRA) In Urine And Feces
timeFrame: Up to 14 days postdose
Secondary outcomes:
measure: Cmax: Maximum Observed Plasma Concentration for Subasumstat and TRA in Plasma and Whole Blood
timeFrame: Predose on Day 1 and at multiple time points postdose up to Day 14
measure: Tmax: Time of First Occurrence of Cmax for Subasumstat and TRA in Plasma and Whole Blood
timeFrame: Predose on Day 1 and at multiple time points postdose up to Day 14
measure: AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Subasumstat and TRA in Plasma and Whole Blood
timeFrame: Predose on Day 1 and at multiple time points postdose up to Day 14
measure: Terminal Disposition Phase Half-life (T1/2z) for Subasumstat and TRA in Plasma and Whole Blood as Permitted by Data
timeFrame: Predose on Day 1 and at multiple time points postdose up to Day 14
measure: Clearance (CL) for Subasumstat and TRA in Plasma and Whole Blood as Permitted by Data
timeFrame: Predose on Day 1 and at multiple time postdose points up to Day 14
measure: Volume of Distribution at Steady-state (Vss) for Subasumstat and TRA in Plasma and Whole Blood as Permitted by Data
timeFrame: Predose on Day 1 and at multiple time points postdose up to Day 14
measure: AUC∞: Area Under the Plasma Concentration-time Curve from Time 0 to Infinity for Subasumstat and TRA in Plasma and Whole Blood as Permitted by Data
timeFrame: Predose on Day 1 and at multiple time points postdose up to Day 14
measure: Cumulative Amount of Unchanged Subasumstat and TRA Excreted into the Urine (Aeurine)
timeFrame: Predose on Day 1 and at multiple time points postdose up to Day 14
measure: Renal Clearance (CLR) for Subasumstat and TRA in Urine
timeFrame: Predose on Day 1 and at multiple time points postdose up to Day 14
measure: Number of Participants With One or More Adverse Events (AEs)
timeFrame: From the start of study drug administration through 30 days after the last dose of study drug (up to approximately 1 year)
measure: Number of Participants With One or More Serious Adverse Events (SAEs)
timeFrame: From the start of study drug administration through 30 days after the last dose of study drug (up to approximately 1 year)
measure: Number of Participants With Abnormal Electrocardiogram Findings
timeFrame: From the start of study drug administration through the last dose of study drug (up to approximately 1 year)
measure: Number of Participants With Abnormal Laboratory Values
timeFrame: From the start of study drug administration through the last dose of study drug (up to approximately 1 year)
measure: Relative Percentage of Circulatory Metabolites in Plasma
timeFrame: Predose on Day 1 and at multiple time points postdose up to Day 14
measure: Relative Percentage Excretory Metabolites in Urine
timeFrame: Predose on Day 1 and at multiple time points postdose up to Day 14
measure: Relative Percentage Excretory Metabolites in Feces
timeFrame: Predose on Day 1 and at multiple time points postdose up to Day 14
Other outcomes:
Locations:
city: Budapest
country: Hungary
facility: Central Hospital of Northern Pest - Military Hospital
city: Budapest
country: Hungary
facility: Pharmaceutical Research Associates Magyarorszag
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References: