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

NCT04969835 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: ALS-6000-101
• Study Type: interventional
• Target: 158
• Locations: 2 countries
• Sites: 9

Brief 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. 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.

Conditions

Salivary Gland Tumor; Urothelial Carcinoma; Ovarian Carcinoma; Breast Cancer; Soft Tissue Sarcoma

Outcome Measures

Primary Outcomes (5)

• Dose-limiting toxicities (DLTs)

  Incidence and nature of DLTs

  Up to 28 days after the first dose of study therapy

• Adverse events (AEs)

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

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

• Laboratory abnormalities

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

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

• Vital signs

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

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

• Cardiac safety

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

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

Secondary Outcomes (8)

• Maximum drug concentration (Cmax) of AVA6000 & Doxorubicin

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

• Area under the curve (AUC) of AVA6000 & Doxorubicin

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

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

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

• Renal clearance (CLr) of AVA6000 & Doxorubicin

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

• Objective response rate (ORR)

  Up to one year

Study Arms (4)

AVA6000 Phase 1a Dose Escalation Q3W

EXPERIMENTAL

Patients 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.

Drug: AVA6000

AVA6000 Phase 1a Dose Escalation Q2W

EXPERIMENTAL

Patients 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.

Drug: AVA6000

AVA6000 Phase 1b Dose Expansion

EXPERIMENTAL

Patients 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.

Drug: AVA6000

AVA6000 Phase 1b Dose Expansion (dose identification)

EXPERIMENTAL

Dosing 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.

Drug: AVA6000

Interventions

AVA6000 DRUG

AVA6000 is a FAP-activated doxorubicin.

AVA6000 Phase 1a Dose Escalation Q2W; AVA6000 Phase 1a Dose Escalation Q3W; AVA6000 Phase 1b Dose Expansion; AVA6000 Phase 1b Dose Expansion (dose identification)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• a. 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
• b) 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
• 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.

You may not qualify if:

• 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).
• 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.

Sponsors & Collaborators

• Avacta Life Sciences Ltd: lead

Study Sites (9)

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

RECRUITING

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Fred Hutchinson Cancer Center

Seattle, Washington, 98109, United States

RECRUITING

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

Glasgow, G12 0YN, United Kingdom

RECRUITING

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

Leeds, LS9 7TF, United Kingdom

RECRUITING

The Royal Marsden, NHS Foundation Trust

London, SM2 5PT, United Kingdom

RECRUITING

The Christie NHS Foundation Trust

Manchester, M20 4BX, United Kingdom

RECRUITING

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

Newcastle upon Tyne, NE7 7DN, United Kingdom

RECRUITING

Weston Park Cancer Centre, Sheffield Teaching Hospitals NHS Foundation Trust

Sheffield, S10 2SJ, United Kingdom

NOT YET RECRUITING

MeSH Terms

Conditions

Salivary Gland Neoplasms; Carcinoma, Transitional Cell; Ovarian Neoplasms; Breast Neoplasms; Sarcoma

Condition Hierarchy (Ancestors)

Mouth Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Neoplasms; Mouth Diseases; Stomatognathic Diseases; Salivary Gland Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Endocrine Gland Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Neoplasms, Connective and Soft Tissue

Study Officials

• Chris Twelves, MD

  St James's University Hospital, Leeds, UK

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Avacta Life Sciences

CONTACT

+44 (0)20 3911 0353; clinicaltrials@avacta.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: June 22, 2021
• First Posted: July 21, 2021
• Study Start: July 16, 2021
• Primary Completion: March 15, 2026
• Study Completion (Estimated): August 15, 2026
• Last Updated: February 4, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

GB (6); US (3)