ML-016 in Advanced Cancer With Lung and/or Liver Involvement

Phase 1/2 Study of ML-016 in Participants With Advanced Cancer With Lung and/or Liver Involvement

This is an open-label, multi-center, phase 1/2 dose-escalation and dose expansion study evaluating the safety, tolerability, pharmacokinetics (PK), and anti-tumor activity of ML-016 in participants with advanced solid tumors with lung and/or liver involvement (primary or metastatic disease).

Study Overview

• Status: Not yet recruiting
• Conditions: Advanced Solid Tumor With Lung and/or Liver Involvement
• Intervention / Treatment: Drug: ML-016

Detailed Description

ML-016 will be administered intravenously as a monotherapy to assess safety, tolerability, pharmacokinetics (PK), and anti-tumor activity in participants with advanced/metastatic solid tumors with lung and/or liver involvement. The involvement of the lung and/or liver can involve primary or metastatic disease.

Participants eligible for treatment include those whose disease is refractory to standard therapeutic options or for which no standard measures with curative intent or likelihood of disease control are available, or such measures are not acceptable to the participant.

Participants will be administered ML-016 on Day 1 of each 21-day cycle. Treatment may continue until the participant's disease worsens or another treatment discontinuation criterion is met.

Phase 1 will be a standard dose escalation design, and Phase 2 will be a dose expansion design evaluating two doses in disease-specific cohorts.

• Study Type: Interventional
• Enrollment (Estimated): 108
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Amanda Jubb, Clinical Project Manager, Southern Star Research; Phone Number: +61 (0)2 9011 6266; Email: ajubb@southernstarresearch.com
• Study Contact Backup: Name: Matt Wagener, VP Clinical Development Operations, BrYet; Email: matt.wagener@bryetpharma.com

Study Locations

• Australia
  • New South Wales
    • Miranda, New South Wales, Australia
      • Southside Cancer Care Centre
      • Principal Investigator: Paul de Souza
      • Contact: Kareena Young; Phone Number: +61 2 8556 9372; Email: kyoung@cancercarefoundation.org.au
    • Wollongong, New South Wales, Australia
      • Illawarra Cancer Care Center, Wollongong Hospital
      • Principal Investigator: Udit Nindra
      • Contact: Carly Leighton; Phone Number: +61 2 4253 4384; Email: carly.leighton@health.nsw.gov.au
  • Queensland
    • Buderim, Queensland, Australia
      • Sunshine Coast Haematology and Oncology Clinic
      • Contact: Elizabeth Gibson; Phone Number: +61 7 5479 0000; Email: egibson@cancercarefoundation.org.au
      • Principal Investigator: Brenton Seidl

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Age ≥18 years old on the day of signing the consent form
2. Histopathological or cytological confirmed diagnosis of advanced (locally advanced or metastatic) solid malignancy which is refractory to standard therapeutic options or for which no standard measures with curative intent or likelihood of disease control are available, or such measures are not acceptable to the participant.
3. Eastern Cooperative Oncology Group Performance Status ≤1

4. The participant has adequate baseline hematologic function, as demonstrated by the following:

   • Hemoglobin ≥8.0 g/dL ,
   • Neutrophil count ≥1.5 x 109/L,
   • Platelets ≥75 x 109/L

5. The participant has adequate baseline kidney function, as demonstrated by the following:

   • Serum creatinine ≤1.5 x ULN, and/or
   • Calculated creatinine clearance ≥60 ml/min using the Cockroft-Gault formula or per institutional standard method

6. The participant has adequate baseline liver function, as demonstrated by the following:

   • Total bilirubin <1.5 x ULN (except for participants with Gilbert syndrome), or
   • Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤3 x ULN, or for participants with liver involvement AST/ALT <5 x ULN
7. Measurable disease using RECIST v 1.1 for solid tumors
8. Evidence of tumor in the lung and/or liver based on imaging studies.
9. For participants with lung metastases, adequate pulmonary function: FEV1, FVC and DLCO ≥50% predicted (corrected for hemoglobin) and no oxygen dependency.
10. For participants with liver metastases, adequate liver function with less than 70% liver involvement as measured by imaging (i.e. CT, MRI, PET/CT, or ultrasound).

11. A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:

    • Documented to be surgically sterile or postmenopausal (amenorrhea 24 months and follicle-stimulating hormone [FSH] ≥30 mIU/mL), OR
    • Practicing true abstinence for at least 28 days prior to study treatment until 120 days after the last dose of study treatment and having a negative serum urine pregnancy test within 72 hours before initiating treatment, OR
    • Using 2 forms of highly effective contraception, including 1 physical barrier (condom or diaphragm) plus another method, such as adequate hormonal method (eg, contraceptive implants, injectables, oral contraceptives) or nonhormonal methods (eg, intrauterine device, spermicidals) from screening or at least 28 days prior to study treatment administration (whichever is earlier) until 120 days after the last dose of study treatment and having a negative serum urine pregnancy test within 72 hours before initiating treatment.

12. Male participants with female partners of childbearing potential may be enrolled if they are:

    • Documented to be surgically sterile (vasectomy), OR
    • Practicing true abstinence until 28 days after the last dose of study treatment, OR
    • Using 2 effective methods of contraception including one barrier method (e.g., condom with spermicide and contraception by female partner) for the duration of time on the study and for 120 days after administration of the last dose of study treatment, unless their partners are infertile or surgically sterile.
13. Minimum life expectancy of 3 months.
14. Ability to read and understand the informed consent form and willingness and ability to give informed consent and demonstrate comprehension of the trial before undergoing any trial assessments.
15. The participant can adhere to the study visit schedule and other protocol requirements, including follow-up for survival assessment.
16. The participant allows tissue biopsy to be available (archive or fresh tissue) unless approved by the Sponsor.

Exclusion Criteria:

1. Participants must not receive prior anticancer therapy or prior investigational therapy within 3 weeks or 5 half-lives, whatever is shorter, or radiation therapy within 3 weeks, and must not undergo major surgery within 4 weeks prior to initiation of treatment on protocol. Palliative radiation therapy is allowed (no palliative radiation may be given to RECIST lesions).
2. The participant must have recovered from all AEs due to previous therapies to Grade ≤1 or baseline. Participants with Grade ≤2 alopecia and/or neuropathy may be eligible. Participants with endocrine-related AEs Grade ≤2 requiring treatment or hormone replacement may be eligible. Prior toxicities that resulted in laboratory abnormalities should have resolved to Grade ≤1 unless a higher-grade abnormality is allowed by the inclusion criteria. If medical therapy is required for the treatment of a laboratory abnormality, the dose and laboratory value(s) should be stable.
3. Symptomatic brain metastasis or leptomeningeal disease requiring treatment. Participants with treated brain metastasis must have stable disease for at least 4 weeks, as evidenced by brain imaging, and the participant must have been asymptomatic off steroids for at least 2 weeks.
4. Cardiac conditions: hypertension (BP > 160/100) despite optimal therapy, ventricular arrhythmias, significantly impaired cardiac function such as unstable angina pectoris, congestive heart failure with New York Heart Association (NYHA) class III or IV, myocardial infarction within the 6 months prior to trial entry; signs of pericardial effusion, serious arrhythmia (including QTc prolongation of >470 ms and/or pacemaker), or prior diagnosis of congenital long QT syndrome
5. Left ventricular ejection fraction <50% or below the lower limit of institutional normal (whichever is higher) on screening echocardiogram.
6. History of anthracycline induced cardiotoxicity
7. History of another primary malignancy (other than basal cell or squamous cell carcinoma, or in situ carcinoma) within 2 years prior to consent.
8. Pregnancy or current breastfeeding or planning to breastfeed.
9. Previous treatment with total cumulative doses of doxorubicin, daunorubicin, idarubicin, and/or other anthracyclines and anthracenediones (≥450 mg/m2).
10. Hypersensitivity to doxorubicin, any of its excipients, or other anthracyclines or anthracenediones or compounds of similar chemical or biologic composition as the study drug.
11. The participant has a history of (non-infectious) pneumonitis or interstitial pulmonary disease that required corticosteroids within the past 3 months or has current pneumonitis or interstitial pulmonary disease.
12. The participant has uncontrolled, clinically significant pulmonary disease (e.g., chronic obstructive pulmonary disease, pulmonary hypertension) that in the opinion of the Investigator would put the participant at significant risk for pulmonary complications during the study.
13. The participant has an active autoimmune disease that required systemic treatment in the past. Participants who have not required systemic treatment for at least two years may be enrolled if permission is provided after discussion with the Medical Monitor (replacement therapy, e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, is not considered a form of systemic treatment, and is allowed).
14. Concurrent severe and/or uncontrolled medical disease that could compromise participation in the study (i.e., uncontrolled diabetes, severe infection requiring intravenous antibiotics, severe malnutrition, chronic severe liver or renal disease).
15. The participant has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating Investigator.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ML-016 Monotherapy; ML-016 participants will be assigned to dose levels upon entry	Drug: ML-016; a pH-sensitive polymeric doxorubicin formulated in a nanoporous silicon microparticle; Other Names: iNPG-pDox

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of dose-limiting toxicities (DLTs) during the DLT assessment period	The incidence of dose-limiting toxicities (DLTs) graded per the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5.0 during the DLT assessment period	Days 1-21 of the first cycle of study treatment (DLT assessment period)
Frequency and severity of adverse events (AEs) and serious AEs (SAEs)	The frequency and severity of adverse events (AEs) and serious AEs (SAEs), treatment discontinuations due to toxicity, and clinical laboratory abnormalities	From first dose of study drug through 30 days following the last dose of study drug
Maximum tolerated dose (MTD) and doses recommended for expansion	Identify the MTD or maximum tested dose and doses recommended for expansion	Days 1-21 of the first cycle of study treatment (DLT assessment period)
Vital Signs: Blood Pressure	Incidence and severity of changes in blood pressure from baseline	Baseline and every cycle of study drug (each cycle is 21 days) through 30 days following the last dose of study drug
Vital Signs: Heart Rate	Incidence and severity of changes in heart rate from baseline	Baseline and every cycle of study drug (each cycle is 21 days) through 30 days following the last dose of study drug
Electrocardiograms (ECGs): QT Interval	Incidence and severity of changes in ECG QT Interval from baseline	Baseline and every cycle of study drug (each cycle is 21 days) through 30 days following the last dose of study drug
Echocardiograms (ECHO): LVEF	Incidence and severity of changes in LVEF from baseline	Baseline and every cycle of study drug (each cycle is 21 days) through 30 days following the last dose of study drug

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease control rate (DCR)	Disease control rate (DCR) is defined as the percentage of patients who have achieved complete response (CR), partial response (PR), or stable disease (SD) per RECIST 1.1.	At least 42 days after the first dose of investigational product
Overall response rate (ORR)	Overall response rate (ORR) is defined as the percentage of patients who have achieved CR or PR per RECIST 1.1.	From first dose of study drug through 12 months following first dose
Duration of response (DOR)	Duration of response (DOR) is defined as the time from the date measurement criteria are first met for patients who achieve PR or CR, to the date measurement criteria are first met for PD.	Time from the date measurement criteria are first met for patients who achieve PR or CR, to the date measurement criteria are first met for PD, assessed up to 12 months.
Progression-free survival (PFS)	Progression-free survival (PFS) is defined as the time from the date of initiation of study treatment to the date measurement criteria are first met for PD or death from any cause, whichever occurs first.	Time from the date of initiation of study treatment to the date measurement criteria are first met for PD or death from any cause, whichever occurs first, assessed up to 12 months.
Time to Progression (TTP)	Time to Progression (TTP) is defined as the time from the date of initiation of study treatment to the date that the measurement criteria are first met for PD.	Time from the date of initiation of study treatment to the date that the measurement criteria are first met for PD, assessed up to 12 months.
Overall Survival (OS)	Overall Survival (OS) is defined as the time from the date of initiation of study treatment to the date of death from any cause.	Time from the date of initiation of study treatment to the date of death from any cause, assessed up to 12 months.
Pharmacokinetic Profile: Cmax	Cmax: Maximum peak plasma concentration	From first dose of study drug through 21 days following the first dose of study treatment (1 cycle)
Pharmacokinetic Profile: AUClast	AUClast: Area under the concentration-time curve from Hour 0 through the last quantifiable concentration time (LQCT), where LQCT is the time at which the last sample with a quantifiable concentration was drawn	From first dose of study drug through 21 days following the first dose of study treatment (1 cycle)
Pharmacokinetic Profile: T½	T½: Half-life	From first dose of study drug through 21 days following the first dose of study treatment (1 cycle)

Collaborators and Investigators

• Sponsor: BrYet US, Inc.
• Collaborators: Southern Star Research
• Investigators: Principal Investigator: Brenton Seidl, MBBS, BSc, FRACP, Cancer Care Foundation Ltd, Sunshine Coast Haematology and Oncology Clinic; Study Director: Apostolia Tsimberidou, MD, PhD, FASCO, FAAAS, BrYet US, Inc.

Study record dates

Study Major Dates

• Study Start (Estimated): August 1, 2026
• Primary Completion (Estimated): August 1, 2027
• Study Completion (Estimated): August 1, 2030

Study Registration Dates

• First Submitted: April 28, 2026
• First Submitted That Met QC Criteria: July 21, 2026
• First Posted (Actual): July 23, 2026

Study Record Updates

• Last Update Posted (Actual): July 23, 2026
• Last Update Submitted That Met QC Criteria: July 21, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Keywords: Neoplasms; Relapsed; Refractory; Metastatic; Solid Tumors; Liver metastasis; Lung metastasis
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Neoplastic Processes; Pathological Conditions, Signs and Symptoms; Neoplasms; Recurrence; Neoplasm Metastasis
• Other Study ID Numbers: BP-ML-016-01

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: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No