Safety and Preliminary Efficacy of SA53-OS in Patients With Locally Advanced or Metastatic Solid Tumors

A Phase 1/2a, Open-Label Study of Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of SA53-OS, an MDM2 Inhibitor, in Patients With Locally Advanced or Metastatic p53 Wild-Type Solid Tumors

The objective of this study is to assess the safety, efficacy, and pharmacokinetics of SA53-OS in adult participants with refractory solid tumors.

The study is comprised of 2 parts: Part 1 called dose escalation, and Part 2a called dose expansion. This study starts with Part 1 where participants who are diagnosed with advanced or metastatic solid tumor cancers receive different doses of SA53-OS (starting with the lowest dose) to find the maximum tolerated dose (MTD) of SA53-OS. Once the MTD of SA53-OS is known, the study continues to Part 2a where participants who are diagnosed with dedifferentiated liposarcoma (DD LPS) or other solid tumor cancers will receive SA53-OS at the MTD.

The study drug, SA53-OS, will be administered for 3 consecutive days every 3 weeks as an oral solution for up to 2 years.

Study Overview

• Status: Recruiting
• Conditions: Solid Tumor
• Intervention / Treatment: Drug: SA53-OS (phase 1); Drug: SA53-OS (phase 2)

Detailed Description

This is a phase 1/2a, open-label, dose escalation study conducted in adult participants with p53 wild-type refractory solid tumors. The study will assess the safety, efficacy, and pharmacokinetics of SA53-OS a novel MDM2 inhibitor capable of selective activation of p53. This enables the p53 tumor suppressor protein to selectively facilitate tumor cell death and growth inhibition.

The study drug, SA53-OS, will be administered for 3 consecutive days every 3 weeks as an oral solution. Phase 1 will consist of a dose escalation study to establish a candidate recommended phase 2 dose (RP2D). Phase 2a will enroll 2 expansion cohorts to establish any preliminary efficacy of SA53-OS in participants with dedifferentiated liposarcoma (DD LPS) with MDM2 amplifications and other p53 wild-type solid tumors as a single agent.

Phase 1 dose escalation:

Escalating doses of SA53-OS will be provided to participants with p53 wild-type refractory solid tumors to determine the RP2D. The MTD is the highest dose of a drug or treatment that does not cause unacceptable side effects in the first cycle. The RP2D considers all available safety, pharmacokinetics, and efficacy data including, the frequency, severity, and manageability of toxicities occurring after Cycle 1.

Phase 1 of the study will start with dose escalation by 2-fold (i.e., 2x preceding dose level) in cohorts of a single participant until Grade 2 or greater toxicity is observed.

When a single Grade 2 or higher toxicity is observed, 3+3 multi-participant cohorts will be treated at the dose in which the Grade 2 or higher toxicity was observed by enrolling another 2 participants at this dose. The 3+3 multi-participant cohorts will follow the standard 3+3 paradigm based on occurrence of any DLT with 50% dose escalation until the MTD is identified.

Phase 2a dose expansion:

The purpose of Phase 2a of the study is to describe any preliminary evidence of efficacy from SA53-OS monotherapy in participants with DD LPS or other p53 wild-type or MDM2 amplified solid tumors. Phase 2a will also be used to confirm the safety and tolerability of the candidate RP2D of SA53-OS determined in Phase 1 of the study, to further describe the toxicity and pharmacokinetics profiles of SA53-OS, and to assess potential biomarkers of sensitivity resistance, and toxicity.

Participants will continue to receive study treatment until either: 1) disease progression; 2) occurrence of unacceptable treatment-related toxicity as per participant or Investigator discretion; 3) the maximum of 2 years of treatment has been reached; or 4) other reason(s) for study treatment discontinuation. In the case of complete response, treatment should be continued for at least 6 months if no other stopping criteria are met, and further treatment can be recommended at the investigator's discretion.

• Study Type: Interventional
• Enrollment (Estimated): 70
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Jill Palmenberg; Phone Number: 520-241-5944; Email: jill.palmenberg@lamassubio.com

Study Locations

• United States
  • Ohio
    • Canton, Ohio, United States, 44718
      • Recruiting
      • Gabrail Cancer Center
      • Contact: Carrie Smith, RN; Phone Number: 330-492-3345; Email: csmith@gabrailcancercenter.com
      • Principal Investigator: Nashat Gabrail, MD
    • Cleveland, Ohio, United States, 44195
      • Recruiting
      • Cleveland Clinic Taussig Cancer Institute
      • Principal Investigator: James Wooley
      • Contact: Cancer Answer Line; Phone Number: 866-223-8100; Email: canceranswer@ccf.org

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Tumor characteristics of participants in Phase 1

  1. Histologically and/or cytologically confirmed diagnosis of advanced or metastatic solid tumor and/or non-Hodgkin lymphoma excluding primary central nervous system malignancy for which no standard effective treatment exists or where that treatment was declined. Participants with non-Hodgkin lymphoma should have failed ≥ 2 prior lines of systemic therapy prior enrollment.
  2. Tumor p53 wild-type.

• Tumor characteristics of participants in Phase 2a

  1. Cohort A: Tumor p53 wild-type with histologically confirmed diagnosis of advanced or metastatic DD LPS (and MDM2 amplification); OR Cohort B: Tumor p53 wild-type in other solid tumor.
  2. Measurable disease by RECIST 1.1.
• 18 years old or older.
• Resolution of clinically relevant toxicity-related to prior anticancer therapies prior to receipt of study treatment to Grade 1 or less.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Participants of childbearing/reproductive potential must agree to use adequate birth control measures during the course of the trial and for at least 3 months after discontinuing study treatment.

Exclusion Criteria:

• Anticipated need for major surgery and/or localized palliative radiation within the next 6 weeks
• Active, untreated central nervous system metastases. Participants with brain metastases identified at Screening may be rescreened after the lesion(s) have been appropriately treated; participants with treated brain metastases should be neurologically stable for 4 weeks post-treatment and prior to study enrollment, and off corticosteroids for at least 2 weeks before start of study treatment, and treated lesions should demonstrate no new growth on the re-screening scan.
• Known HIV infection or active hepatitis B or C infection.
• Thrombotic event requiring active and ongoing anticoagulation within the last 6 months prior to study treatment.
• Myocardial infarction within the last 6 months prior to study treatment.
• Significant cardiovascular disease including unstable angina pectoris, uncontrolled hypertension or arrhythmia, congestive heart failure New York Heart Association (NYHA) Class III or IV related to primary cardiac disease, uncontrolled ischemic or severe vascular heart disease.
• A history of additional risk factors for Torsades de Pointes (TdP) (e.g., heart failure, hypokalemia, family history of Long QT Syndrome)
• Known bleeding disorder (e.g., hemophilia, von Willebrand disease).
• Conditions that may predispose to major bleeding (e.g., active GI ulcers, upper or lower GI bleedings in the last 6 months, significant hemoptysis in the last 6 months, tumor invasion of major vessels, etc.). Conditions that have been treated may be allowed if resolution of the risk is documented.
• Use or indication for full dose anticoagulation or anti-platelet therapy including low dose aspirin.
• Women who are pregnant or lactating.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase 1; Dose escalation phase	Drug: SA53-OS (phase 1); Dose escalation phase in which participants receive SA53-OS on 3 consecutive days every 3 weeks for a maximum of 2 years. Single participant cohorts will be enrolled until a Grade 2 or greater toxicity is observed and then 3+3 multi-participant cohorts will be enrolled until the MTD is identified.
Experimental: Phase 2; Cohort A: DDLPS (MDM2 amplified and p53 wild-type) Cohort B: other p53 wild-type solid tumors	Drug: SA53-OS (phase 2); Dose expansion phase in which participants receive SA53-OS on 3 consecutive days every 3 weeks for a maximum of 2 years at the MTD identified in phase 1.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 1: Incidence of DLT	Incidence of DLT in Cycle 1 (Day 1 to 21)	21 days
Phase 1 and 2: Adverse events	Frequency of adverse events	Approximately 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 1: Peak plasma concentration	Determine the pharmacokinetic profile of SA53-OS (Cmax)	Day 4
Phase 1: Area under the plasma concentration versus time curve between 0 and 24 hours	Determine the pharmacokinetic profile of SA53-OS (AUC0-24)	Day 4
Phase 1: Half-life	Determine the pharmacokinetic profile of SA53-OS (T1/2)	Day 4
Phase 2: Objective response rate (ORR)	Participants achieving ORR defined as complete response (CR) rate plus partial response (PR) rate. CR: Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.	Approximately 2 years
Phase 2: Progression free survival (PFS)	Participants not meeting the definition for progressive disease	Approximately 2 years
Phase 2: Overall survival	To evaluate overall survival	Approximately 2 years
Phase 2: Duration of response	Duration of response will be evaluated in responders	Approximately 2 years
Phase 2: Complete response rate	Participants achieving CR defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm.	Approximately 2 years
Phase 2: Stable disease rate	Participants achieving stable disease defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease.	Approximately 2 years
Phase 2: Disease control rate	Participants achieving CR + PR + stable disease	Approximately 2 years

Collaborators and Investigators

• Sponsor: Lamassu Bio Inc
• Investigators: Study Director: Gabi Hanna, MD, Lamassu Bio

Study record dates

Study Major Dates

• Study Start (Actual): March 10, 2025
• Primary Completion (Estimated): March 1, 2026
• Study Completion (Estimated): December 1, 2028

Study Registration Dates

• First Submitted: August 15, 2024
• First Submitted That Met QC Criteria: August 27, 2024
• First Posted (Actual): August 29, 2024

Study Record Updates

• Last Update Posted (Estimated): June 5, 2025
• Last Update Submitted That Met QC Criteria: June 3, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Keywords: solid tumors; p53; liposarcoma; Advanced or metastatic solid tumors; p53 wild-type tumor; MDM2 inhibitor; dedifferentiated liposarcoma (DD LPS)
• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: LB-SA53-101

Drug and device information, study documents

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