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

A Phase 1/2a Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of NTS071 in Subjects With Advanced Solid Tumors Harboring a TP53 Y220C Mutation

This study is to evaluate the safety, tolerability, PK, and preliminary efficacy of NTS071 in adults with TP53 Y220C-mutated solid tumors.

Study Overview

• Status: Recruiting
• Conditions: Advanced Solid Tumors
• Intervention / Treatment: Drug: NTS071

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 Type: Interventional
• Enrollment (Estimated): 220
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Yan Xu; Phone Number: +86 13585878226; Email: yan.xu@allonutshell.com

Study Locations

• China
  • Shanghai, China, 200032
    • Recruiting
    • Shanghai
• United States
  • Texas
    • San Antonio, Texas, United States, 78201
      • Recruiting
      • Next Oncology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: NTS071; Single arm	Drug: NTS071; Oral administration

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 1: Number of dose-limiting toxicity (DLT)	Incidence of dose-limiting toxicity (DLT) events	The first 26 days of treatment (Cycle 1) per patient
Phase 1: incidence of adverse events (AE), serious adverse events (SAEs)	Adverse events will be assessed by investigator(s) according to NCI-CTCAE v5.0	up to 30 days after the last administration
Phase 2a: Overall Response Rate (ORR)	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)	Up to 3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 1/2a: area under the curve (AUC)	PK parameters to be evaluated for NST071 including area under the curve (AUC) will be determined when appropriate.	Up to 2 years
Phase 1/2a: maximum concentration (Cmax)	PK parameters to be evaluated for NTS071 including maximum concentration (Cmax) will be determined when appropriate.	Up to 2 years
Phase 1/2a: half-life (t1/2) of NTS071	PK parameters to be evaluated for NTS071 including half-life (t1/2) will be determined when appropriate.	Up to 2 years
Phase 1/2a: trough observed concentrations (Ctrough/Ctau)	Pharmacokinetic parameters will be determined by non-compartmental methods using pharmacokinetic profile of NTS071	Up to 2 years
Phase 1: Objective response rate (ORR)	To evaluate the preliminary antitumor activity of NTS071	Up to 3 years
Phase 1/2a: duration of response (DoR)	To evaluate the preliminary anti-tumor activity of NTS071	Up to 3 years
Phase 1/2a: disease control rate (DCR)	To evaluate the preliminary antitumor activity of NTS071	Up to 3 years
Phase 1/2a: progression-free survival (PFS)	To evaluate the preliminary antitumor activity of NTS071	Up to 3 years
Phase 1/2a: Overall survival (OS)	To evaluate the preliminary antitumor activity of NTS071	Up to 3 years

Collaborators and Investigators

• Sponsor: Nutshell Therapeutics (Shanghai) Co., LTD.

Study record dates

Study Major Dates

• Study Start (Actual): August 4, 2025
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2029

Study Registration Dates

• First Submitted: July 2, 2025
• First Submitted That Met QC Criteria: July 2, 2025
• First Posted (Actual): July 11, 2025

Study Record Updates

• Last Update Posted (Actual): June 17, 2026
• Last Update Submitted That Met QC Criteria: June 15, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Advanced Solid Tumors; TP53 Y220C
• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: NTS071-101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No