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Salivary Gland TumorPhase 1NCT04969835

A Study Evaluating the Safety, Pharmacokinetics and Early Efficacy of AVA6000 in Solid Tumours

A Phase 1 study testing AVA6000 in people with Salivary Gland Tumor and Urothelial Carcinoma, run by Avacta Life Sciences Ltd at 9 sites in 2 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

This is a first-in-human (FIH), Phase 1 open-label, multicentre dose escalation study investigating AVA6000 monotherapy administered intravenously in patients with locally advanced (unresectable) or metastatic solid tumours that are likely to be FAP positive. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
AVA6000
Could I receive a placebo?
No, everyone receives an active treatment
How many people
158 participants
Where
9 sitesin 2 countries
Study dates
16 Jul 2021to 6 Aug 2027
Phase
Phase 1
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • The patient has been fully informed about the study and has signed the Informed Consent Form.
  • Male or female patients, ≥ 18 years of age.
  • a) Phase 1a: patients with tumours reported to be FAP positive with histological or cytological confirmation of a locally advanced (unresectable) and/or metastatic:
  • salivary gland, urothelial, ovarian, or breast carcinoma, who have either relapsed or progressed on SoC treatment or are intolerant or nonamenable to SoC treatment; OR b. soft-tissue sarcoma who: i. is treatment naïve in the locally advanced (unresectable) or metastatic setting and anthracycline naïve (any setting) and would otherwise be a candidate for doxorubicin hydrochloride treatment; OR ii. has received a total doxorubicin dose of < 150mg/m2 (any setting (< 2 cycles of 75 mg/m2 Q21 days) and has discontinued due to intolerance or toxicity related to doxorubicin
  • Phase 1b: patients with histological or cytological confirmation of a locally advanced (unresectable) and/or metastatic tumour of one of the following types:
  • High grade soft tissue sarcoma: histologically proven locally advanced or metastatic, unresectable progressive or recurrent DDLS or UPS who have received 0 or 1 prior lines of therapy in the locally advanced or metastatic setting
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  • SGC: Locally advanced or metastatic salivary gland confirmed by histopathology that cannot be completely resected by surgery who have received 0 or 2 prior lines of therapy in the locally advanced or metastatic setting. In addition, patients with adenoid cystic carcinoma subtypes must not have received prior cytotoxic therapy for locally advanced or metastatic disease. Adenoid cystic carcinoma subtype may be capped at 15 patients (assuming cohort of approximately 30 patients)
  • TNBC: Locally advanced or metastatic triple negative breast cancer confirmed by histopathology who have received any prior therapy in the locally advanced or metastatic setting. Patients must be BRCA wild-type.
  • In Phase 1b, patients must meet the following additional criteria:
  • Patients must demonstrate (as documented, per the investigator's assessment), radiological disease progression over the 6 months (±2 months) prior to screening. However, this requirement does not apply if the patient is newly diagnosed, recurrent or newly metastatic.
  • Patients must have measurable disease per RECIST.
  • Patients with high grade soft tissue sarcoma or salivary gland cancer must not have previously received an anthracycline-based therapy.
  • Patients with TNBC may receive up to 250mg/m2 of prior doxorubicin (or an equivalent anthracycline). Prior anthracycline based therapy must have been completed at least 6 months before the planned Cycle 1 Day 1 AVA6000 infusion. Prior anthracycline use must have been in the adjuvant or neoadjuvant setting only.
  • Patients must provide at least 1 tissue sample collection, either archival or fresh tissue (approximately 10 slides) unless the biopsy is medically not able to be performed or the principal investigator deems it is not medically feasible.
  • Has a life expectancy of ≥12 weeks, in the opinion of the investigator.
  • Has an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1.
  • Has recovered from all acute toxic effects of any prior radiotherapy, chemotherapy, or surgical procedure (must have resolved to CTCAE grade ≤1 or returned to baseline, except alopecia and peripheral neuropathy, which can be up to CTCAE grade 2).
  • Has adequate haematological function (applies only to patients not receiving therapeutic anticoagulation; patients receiving therapeutic anticoagulation should be on a stable dose):
  • Absolute Neutrophil count (ANC) of ≥1.5 × 109 cells/L.
  • Haemoglobin ≥9.0 g/dL.
  • Platelet count of ≥75,000/µL.
  • International normalised ratio (INR) and activated partial thromboplastin time (aPTT) ≤1.5 times the upper limit of normal (ULN).
  • Has adequate liver function:
  • Total bilirubin below ULN (except for patients with Gilbert's Syndrome who must have a total bilirubin <3 × ULN).
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 × ULN (in patients with liver metastases, <5 × ULN is allowed).
  • Alkaline phosphatase (ALP) <5 × ULN in patients with documented liver or bone metastases, or ALP < 2 × ULN in patients without documented metastases.
  • Has adequate renal function (creatinine clearance ≥50 mL/min by Cockcroft-Gault formula) or patients with normal plasmatic creatinine despite creatinine clearance < 50 mL/min as per Cockcroft-Gault formula are eligible for the study.
  • Women of childbearing potential (WOCBP) and women who have ≤ 2 years amenorrhea after start of menopause: has a negative serum pregnancy test within 7 days prior to Cycle 1 Day 1.
  • Contraception requirements:
  • Female patients of childbearing potential must agree to remain abstinent (refrain from heterosexual intercourse) or use a highly effective contraceptive method (Pearl Index failure rate <1% per year) during the treatment period and for at least 6 months after the last dose of study drug.
  • Male patients with female partners of childbearing potential must agree to using 2 acceptable methods of contraception (Pearl Index failure rate <1% per year), including a barrier method (with or without spermicide) during the treatment period and for at least 6 months after the last dose of study drug.
  • Male patients must agree to refrain from sperm donation during the treatment period and for at least 6 months after the last dose of study drug.
  • All patients should have peripheral veins or central line that are, in the opinion of the Investigator or delegate, suitable for peripheral or central intravenous infusion of AVA6000.
  • The patient is willing and able to comply with the protocol, including any PK blood sampling requirements and agrees to return to hospital for follow-up visits and examinations.

Who cannot join

  • Has received trastuzumab within 7 months of the planned Cycle 1 Day 1 AVA6000 infusion.
  • Has received a prior total cumulative anthracycline dose of ≥ 350 mg/m2 doxorubicin (or equivalent anthracycline dose).
  • Has clinically significant or untreated central nervous system (CNS) metastases or leptomeningeal disease requiring treatment, as determined by the Investigator.
  • Patients who have any history of an active (requiring treatment) other malignancy (except any in-situ carcinoma, non-melanoma skin carcinoma and early prostate cancer with a normal PSA) within 2 years of study entry.
  • Has a significant, uncontrolled, concomitant disease that could affect compliance with the protocol.
  • In the opinion of the investigator, has uncontrolled hypertension (systolic blood pressure >150 mm Hg and/or diastolic blood pressure >100 mm Hg), unstable angina, CHF (New York Heart Association (NYHA) Class >II), left ventricular ejection fraction (LVEF) <55% or the low limit of institutional normal limit (whichever is lower) by echocardiogram (ECHO), serious cardiac arrhythmia requiring treatment (exceptions include atrial fibrillation, paroxysmal supraventricular tachycardia), history of myocardial infarction within 6 months prior to Cycle 1 Day 1, or history of uncontrolled cardiovascular disease or high-sensitivity troponin above normal at baseline (T or I).
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  • Has a screening baseline mean corrected QTcF interval by Fridericia (QTcF) of >480 msec. Electrocardiograms (ECGs) will be evaluated locally at the investigator site. Has any clinically significant abnormalities in rhythm, conduction, or morphology of resting ECG (e.g., complete left bundle branch block, third degree heart block, second degree heart block, PR interval >250 msec). Has any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalaemia, congenital long QT syndrome, known family history of long QT syndrome or unexplained sudden death under 40 years of age in first degree relatives or any concomitant medication known to prolong the QT interval, a baseline resting bradycardia <45 beats/min or a baseline resting tachycardia of >100 beats/min.
  • HIV infection:
  • Patients with an AIDS-defining infection within 12 months of planned study Day 1.
  • Patients on anti-retroviral treatment who are not established on anti-retroviral treatment for ≥4 weeks and who have a viral load > 400 copies/mL prior to study Day 1.
  • Active hepatitis B (HBV) or hepatitis C (HCV) infection defined as:
  • Has a positive hepatitis B surface antigen (HBsAG) test at screening. Patients with a past or resolved HBV infection (defined as having a negative HBsAG test and a positive antibody to hepatitis B core antigen [antiHBc] antibody test) are eligible.
  • Patients positive for HCV antibody are eligible only if PCR is negative for HCV RNA.
  • Chronic HBV (HbSAg positive, undetectable or low HBV DNA and normal ALT).
  • Patients with active disease who have not on/initiated anti-retroviral treatment prior to study Day 1.
  • Patients with untreated HCV infection or have not completed treatment for HCV infection.
  • Patients with treated HCV infection but with a HCV viral load above the level of quantification.
  • Has a severe infection (requiring iv treatment) within 21 days prior to Cycle 1, Day 1 including, but not limited to, hospitalisation for complications of infection, bacteraemia, or severe pneumonia.
  • Has any other clinically significant active disease, metabolic dysfunction, physical examination finding, clinical laboratory finding, or reasonable suspicion of a disease or condition that would contraindicate the use of an investigational drug in the opinion of the investigator.

Trial locations and contacts

9 sites in 2 countries.

9 sites in 2 countries

United Kingdom6 sites

  • The Beatson West of Scotland Cancer Centre, NHS Greater Glasgow & Clyde

    Glasgow, G12 0YN

  • St James's University Hospital, The Leeds Teaching Hospitals NHS Trust

    Leeds, LS9 7TF

  • The Royal Marsden, NHS Foundation Trust

    London, SM2 5PT

  • The Christie NHS Foundation Trust

    Manchester, M20 4BX

  • The Freeman Hospital, Newcastle-upon-Tyne NHS Foundation Trust

    Newcastle upon Tyne, NE7 7DN

  • Weston Park Cancer Centre, Sheffield Teaching Hospitals NHS Foundation Trust

    Sheffield, S10 2SJ

Other trials in United Kingdom

United States3 sites

  • University of Texas MD Anderson Cancer Center

    Houston, Texas, 77030

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

  • Fred Hutchinson Cancer Center

    Seattle, Washington, 98109

Other trials in United States

About this study

Official title: A Phase 1, Open Label, Dose-Escalation and Expansion Study to Evaluate the Safety, Pharmacokinetics and Initial Therapeutic Activity of AVA6000, a Novel FAP-activated Doxorubicin Administered Intravenously in Patients With Locally Advanced or Metastatic Selected Solid Tumours

This is a first-in-human (FIH), Phase 1 open-label, multicentre dose escalation study investigating AVA6000 monotherapy administered intravenously in patients with locally advanced (unresectable) or metastatic solid tumours that are likely to be FAP positive. The study consists of an initial Phase 1a dose escalation portion and a subsequent Phase 1b dose expansion portion upon completion of the dose escalation portion.

Read the detailed description

Phase 1a (Dose Escalation): The dose-escalation portion is designed to evaluate the safety, tolerability and MTD and/or RP2D of AVA6000, administered as monotherapy in two schedules: Day 1 of a 21-day cycle (Q3W schedule) and Day 1 of a 14-day cycle (Q2W schedule).

Phase 1b (Dose Expansion): The dose-expansion arm is based on review of data in the dose escalation phase, with AVA6000 administered at the recommended dose for expansion.

Being tested
AVA6000
Medical subject headings
Salivary Gland Neoplasms, Carcinoma, Transitional Cell, Ovarian Neoplasms, Breast Neoplasms, Sarcoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AVA6000Drug

    AVA6000 is a FAP-activated doxorubicin.

Study groups in NCT04969835
Study groupRoleWhat they receive
AVA6000 Phase 1a Dose Escalation Q3WExperimentalPatients in this arm will receive escalating doses of AVA6000 following a 3+3 design, Q3W until disease progression, unacceptable toxicities, withdrawal from treatment for other reasons, reaching maximum lifetime cumulative exposure to doxorubicin (or other anthracyclines), or death, whichever occurs first.
Receives: Drug: AVA6000
AVA6000 Phase 1a Dose Escalation Q2WExperimentalPatients in this arm will receive escalating doses of AVA6000 following a 3+3 design, Q2W until disease progression, unacceptable toxicities, withdrawal from treatment for other reasons, reaching maximum lifetime cumulative exposure to doxorubicin (or other anthracyclines), or death, whichever occurs first.
Receives: Drug: AVA6000
AVA6000 Phase 1b Dose ExpansionExperimentalPatients in this arm will receive AVA6000 at the recommended dose for expansion, until disease progression, unacceptable toxicities, withdrawal from treatment for other reasons, or death, whichever occurs first.
Receives: Drug: AVA6000
AVA6000 Phase 1b Dose Expansion (dose identification)ExperimentalDosing on this arm will occur at RDE -1 to identify the optimal biologic dose of AVA6000. Patients on this arm will receive AVA6000 until disease progression, unacceptable toxicities, withdrawal from treatment for other reasons, or death, whichever occurs first.
Receives: Drug: AVA6000

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Dose-limiting toxicities (DLTs)

    Incidence and nature of DLTs

    Measured: Up to 28 days after the first dose of study therapy

  2. Adverse events (AEs)

    Incidence and severity of treatment-emergent (TE) and treatment-related adverse events (TRAEs) and Seious Adverse Events (SAEs).

    Measured: From Day 1 until up to 30 days after last dose of study drug.

  3. Laboratory abnormalities

    Incidence of clinically significant laboratory abnormalities and changes in laboratory values (haematology, coagulation, serum chemistry and urinalysis).

    Measured: From Day 1 until up to 30 days after last dose of study drug.

  4. Vital signs

    Clinically significant changes in vital signs, physical examination findings, and ECG findings.

    Measured: From Day 1 until up to 30 days after last dose of study drug.

  5. Cardiac safety

    Clinically significant reduction in LVEF (fallen by > 10% to below the lower level of institutional normal (as assessed by ECHO).

    Measured: From Day 1 until up to 30 days after last dose of study drug.

Secondary outcomes (8)

  1. Maximum drug concentration (Cmax) of AVA6000 & Doxorubicin

    Cmax (maximum plasma concentration) of AVA6000 and Doxorubicin after administration after Cycle 1 and 2 for 72 hours post-dose.

    Measured: Cycle 1 and Cycle 2, 0-72 hours post dose (Dose Escalation)

  2. Area under the curve (AUC) of AVA6000 & Doxorubicin

    AUC (Area under the curve) of AVA6000 and Doxorubicin after administration after Cycle 1 and 2 for 72 hours post-dose.

    Measured: Cycle 1 and Cycle 2, 0-72 hours post dose (Dose Escalation)

  3. Elimination half-life (t1/2) of AVA6000 & Doxorubicin

    t1/2 (Elimination half-life) of AVA6000 and Doxorubicin after administration after Cycle 1 and 2 for 72 hours post-dose.

    Measured: Cycle 1 and Cycle 2, 0-72 hours post dose (Dose Escalation)

  4. Renal clearance (CLr) of AVA6000 & Doxorubicin

    CLr (Renal clearance) of AVA6000 and Doxorubicin after administration after Cycle 1 and 2 for 72 hours post-dose.

    Measured: Cycle 1 and Cycle 2, 0-72 hours post dose (Dose Escalation)

  5. Objective response rate (ORR)

    ORR is defined as the proportion of patients achieving a best overall response of confirmed partial responses (PR) or complete response (CR), per Response Evaluation Criteria in Solid Tumors (RECIST 1.1).

    Measured: Up to one year

  6. Duration of Response (DoR)

    DoR is defined as the duration of time from date of first response to date of disease progression, as per RECIST v1.1

    Measured: Up to one year

  7. Progression-free-survival (PFS)

    PFS is defined as the time from the date of the first dose to the date of the first documentation of confirmed disease progression or death, whichever occurs first, as per RECIST v1.1

    Measured: Up to one year

  8. Overall survival (OS)

    Overall survival (OS), defined as the date of first dose) to the occurrence of death from any cause

    Measured: Up to one year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 Jul 2021
  2. Study start16 Jul 2021
  3. Primary completion7 Aug 2026
  4. Study completion6 Aug 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Model description
This study will follow a standard 3+3 dose escalation design in Phase 1a to evaluate the safety, tolerability, and MTD of two AVA6000 administration schedules (Q3W and Q2W). The Phase 1b dose expansion regimen was selected based upon completion of the Phase 1a portion. A cohort at RDE -1 was added to select the optimal biologic dose. Cardiac safety will be assessed at cumulative exposure above the standard lifetime maximum exposure of doxorubicin.
Masking
None (open label)
Enrolment
158 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04969835
Sponsor's protocol ID
ALS-6000-101
Status last verified
Sep 2026
First submitted
22 Jun 2021
Last updated
2 Oct 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No: Qualified researchers may request access to individual patient-level data through clincialtrials@avacta.com

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing AVA6000 in people with Salivary Gland Tumor and Urothelial Carcinoma, run by Avacta Life Sciences Ltd at 9 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 34 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 2 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 9 sites in United Kingdom, United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Dose-limiting toxicities (DLTs) (time frame: Up to 28 days after the first dose of study therapy). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04969835.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Oct 2026.

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