Advanced Solid Tumors
Conditions
Keywords
Advanced Solid Tumors, TP53 Y220C
Brief summary
This study is to evaluate the safety, tolerability, PK, and preliminary efficacy of NTS071 in adults with TP53 Y220C-mutated solid tumors.
Detailed description
This is a Phase 1/2a, first-in-human, open-label, multi-center study with the aim of exploring the safety, tolerability, PK, and preliminary efficacy of NTS071 in subjects with unresectable locally advanced or metastatic solid tumors containing a TP53 Y220C mutation. This study includes two parts: Phases 1 and 2a. The Phase 1 part consists of the dose escalation and backfill part; The Phase 2a part consists of the cohort expansion part.
Interventions
DRUGNTS071
Oral administration
Sponsors
Nutshell Therapeutics (Shanghai) Co., LTD.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Male or female subjects, ≥ 18 years 2. Advanced solid tumors with TP53 Y220C mutation 3. Previously treated with one or more lines of anticancer therapy and progressive disease 4. At least one measurable lesion according to RECIST version 1.1 criteria 5. Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1 6. Adequate organ and bone marrow function
Exclusion criteria
1. Known CNS primary tumor and active or untreated CNS metastases 2. History of another primary malignancy that has been diagnosed or required therapy within the past 2 years 3. Toxicities of prior therapy have not been resolved to ≤ Grade 1 or to baseline 4. Significant cardiovascular disease, including congestive heart failure 5. Known hepatitis B, hepatitis C, or human immunodeficiency virus infection that is active 6. Have a known psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with the requirements of the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1: Number of dose-limiting toxicity (DLT) | The first 26 days of treatment (Cycle 1) per patient | Incidence of dose-limiting toxicity (DLT) events |
| Phase 1: incidence of adverse events (AE), serious adverse events (SAEs) | up to 30 days after the last administration | Adverse events will be assessed by investigator(s) according to NCI-CTCAE v5.0 |
| Phase 2a: Overall Response Rate (ORR) | Up to 3 years | ORR is defined as the percentage of participants with confirmed complete response (CR) or partial response (PR) by Response Evaluations Criteria in Solid Tumors Version 1.1 (RECIST v1.1) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1/2a: area under the curve (AUC) | Up to 2 years | PK parameters to be evaluated for NTS071 including area under the curve (AUC) will be determined when appropriate. |
| Phase 1/2a: maximum concentration (Cmax) | Up to 2 years | PK parameters to be evaluated for NTS071 including maximum concentration (Cmax) will be determined when appropriate. |
| Phase 1/2a: half-life (t1/2) of NTS071 | Up to 2 years | PK parameters to be evaluated for NTS071 including half-life (t1/2) will be determined when appropriate. |
| Phase 1/2a: trough observed concentrations (Ctrough/Ctau) | Up to 2 years | Pharmacokinetic parameters will be determined by non-compartmental methods using pharmacokinetic profile of NTS071 |
| Phase 1: Objective response rate (ORR) | Up to 3 years | To evaluate the preliminary antitumor activity of NTS071 |
| Phase 1/2a: duration of response (DoR) | Up to 3 years | To evaluate the preliminary anti-tumor activity of NTS071 |
| Phase 1/2a: disease control rate (DCR) | Up to 3 years | To evaluate the preliminary antitumor activity of NTS071 |
| Phase 1/2a: progression-free survival (PFS) | Up to 3 years | To evaluate the preliminary antitumor activity of NTS071 |
| Phase 1/2a: Overall survival (OS) | Up to 3 years | To evaluate the preliminary antitumor activity of NTS071 |
Countries
China, United States
Contacts
CONTACTYan Xu
Outcome results
None listed