A Study of Safety, Tolerability and Preliminary Efficacy of NTS071 in Subjects With Advanced Solid Tumors Harboring a TP53 Y220C Mutation

Not Applicable

Not yet recruiting

• Conditions: Advanced Solid Tumors
• Interventions: Drug: NTS071

• Registration Number: NCT07060989
• Lead Sponsor: Nutshell Therapeutics (Shanghai) Co., LTD.

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.

Study Timeline

• Status Verified: 2025-07
• Study First Submitted: 2025-07-02
• Study First Submitted QC: 2025-07-02
• Last Update Submitted: 2025-07-02
• Study First Posted: 2025-07-11
• Last Update Posted: 2025-07-11
• Study Start: 2025-08-01
• Primary Completion: 2028-12
• Study Completion: 2029-12-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 220

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
NTS071	NTS071	Single arm

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
Phase 1/2a: disease control rate (DCR)	Up to 3 years	To evaluate the preliminary antitumor activity of NTS071
Phase 1/2a: area under the curve (AUC)	Up to 2 years	PK parameters to be evaluated for NST071 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: 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

Trial Locations

Locations (2)

Next Oncology; 🇺🇸 San Antonio, Texas, United States

Shanghai; 🇨🇳 Shanghai, China