POL6326 (Balixafortide) Plus Nab-paclitaxel or Eribulin in Patients With HER2-negative Advanced Breast Cancer

NCT04826016 | Withdrawn Phase 1

• 2 other identifiers: MedOPP2382020-004203-13
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a multicenter Phase Ib/II, open-label, dose-escalation study to optimize POL6326 (balixafortide) in combination with nab-paclitaxel or eribulin in patients with HER2-negative advanced breast cancer.

Conditions

Advanced Breast Cancer

Outcome Measures

Primary Outcomes (2)

• PHASE Ib: Maximum tolerated dose (MTD) / Recommended phase II dose (RP2D) of POL6326 (balixafortide)

  MTD/RP2D, based on the incidence of Dose limiting toxicities (DLT) defined as the highest dose level explored at which up to one third of evaluable patients develop a DLT during the first treatment cycle.

  12 - 24 months

• PHASE 2: Progression free survival (PFS)

  To assess the efficacy of POL6326 (balixafortide) in combination with either eribulin or nab-paclitaxel in terms of PFS as per RECIST v. 1.1 in patients with HER2-negative ABC.

  from treatment initiation until objective tumor progression or death (at least 4.5 months)

Secondary Outcomes (23)

• PHASE Ib: PFS

  from treatment initiation until objective tumor progression or death (at least 4.5 months)

• PHASE Ib: Overall response rate (ORR)

  from baseline until end of study (will occur when all patients have discontinued treatment or 12 month after the last patient was enrolled on the study plus the safety follow up window of 28 days after last dose of study treatment in the last patient)

• PHASE Ib: clinical benefit rate (CBR)

  at least 6 months

• PHASE IB: duration of response (DoR)

  from the first occurrence of a documented objective response to disease progression or death, up to 12 months

• PHASE Ib: maximum tumor shrinkage (MTS)

  from baseline until end of study (will occur when all patients have discontinued treatment or 12 month after the last patient was enrolled on the study plus the safety follow up window of 28 days after last dose of study treatment in the last patient

Study Arms (4)

PHASE Ib - ARM A: POL6326 (balixafortide) + eribulin

EXPERIMENTAL

On day 1 and 8 of each 21-day cycle (+/- 1 day) fixed eribulin dose of 1.23 mg/m2 (equivalent to 1.4 mg/m2 eribulin mesylate) combined with increasing doses of POL6326 (balixafortide) starting at a dose of 11 mg/Kg will be administered both intravenously. POL6326 (balixafortide) will be administered following a biphasic regimen (0,5 mg/Kg of POL6326 (balixafortide) dose during the first 30 min of treatment, the remaining dose during the following 3 h and 30 min for a total of 4h. Eribulin will be administered within 45 min after the end of the POL6326 (balixafortide) infusion over 2 to 5 min. Up to 4 additional cohorts may be introduced

Drug: POL6326; Drug: Eribulin

PHASE Ib - ARM B: POL6326 (balixafortide) + nab-paclitaxel

EXPERIMENTAL

On day 1, 8 and 15 of each 28-day cycle (+/- 1 day) fixed nab-paclitaxel dose of 100 mg/m2 combined with increasing doses of POL6326 (balixafortide) starting at a dose of 5.5 mg/Kg will be administered both intravenously. POL6326 (balixafortide) will be administered following a biphasic regimen (0,5 mg/Kg of POL6326 (balixafortide) dose during the first 30 min of treatment, the remaining dose during the following 3 h and 30 min for a total of 4h. Nab-paclitaxel will be administered within 45 min after the end of the POL6326 (balixafortide) infusion over 30 min. Up to 5 additional cohorts may be introduced

Drug: POL6326; Drug: Nab paclitaxel

PHASE 2 - ARM A: POL6326 (balixafortide) + eribulin

EXPERIMENTAL

MTD/RDP2 POL6326 (balixafortide) (from arm A phase Ib) will be administered over 4h intravenous infusion (biphasic regimen as detailed above/ phase Ib) followed by 1.4 mg/m2 eribulin over 5 min Intravenous infusion on days 1 and 8 in 21-day cycles (+/- 1 day).

Drug: POL6326; Drug: Eribulin

PHASE 2 - ARM B: POL6326 (balixafortide) + nab-paclitaxel

EXPERIMENTAL

MTD/RDP2 POL6326 (balixafortide) (from arm B phase Ib) will be administered over 4h intravenous infusion (biphasic regimen as detailed above/ phase Ib) followed by 100 mg/m2 nab-paclitaxel over 30 min Intravenous infusion on days 1, 8 and 15 in 28-day cycles (+/- 1 day).

Drug: POL6326; Drug: Nab paclitaxel

Interventions

POL6326 DRUG

POL6326 (balixafortide): starting dose at 5.5 mg/Kg. Intravenous administration on day 1 and 8 of each 21-day cycle (+/- 1 day) (Phase Ib ARM A and Phase II ARM A ) or on day 1, 8 and 15 of each 28-day cycle (Phase Ib ARM B and Phase 2 ARM B) (+/- 1 day).

Also known as: Balixafortide

PHASE 2 - ARM A: POL6326 (balixafortide) + eribulin; PHASE 2 - ARM B: POL6326 (balixafortide) + nab-paclitaxel; PHASE Ib - ARM A: POL6326 (balixafortide) + eribulin; PHASE Ib - ARM B: POL6326 (balixafortide) + nab-paclitaxel

Eribulin DRUG

Eribulin: 1.23 mg/m2 (equivalent to 1.4 mg/m2 eribulin mesylate). Intravenous administration on day 1 and 8 of each 21-day cycle (+/- 1 day) (Phase Ib ARM A and Phase II ARM A ) or on day 1, 8 and 15 of each 28-day cycle (Phase Ib ARM B and Phase 2 ARM B) (+/- 1 day).

Also known as: Halaven

PHASE 2 - ARM A: POL6326 (balixafortide) + eribulin; PHASE Ib - ARM A: POL6326 (balixafortide) + eribulin

Nab paclitaxel DRUG

Nab-paclitaxel: 100 mg/m2. Intravenous administration on day 1 and 8 of each 21-day cycle (+/- 1 day) (Phase Ib ARM A and Phase II ARM A) or on day 1, 8 and 15 of each 28-day cycle (Phase Ib ARM B and Phase 2 ARM B) (+/- 1 day).

Also known as: Abraxane

PHASE 2 - ARM B: POL6326 (balixafortide) + nab-paclitaxel; PHASE Ib - ARM B: POL6326 (balixafortide) + nab-paclitaxel

Eligibility Criteria

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

You may qualify if:

• Female patients ≥18 years of age with histologically confirmed invasive breast cancer.
• Able to understand and willing to sign an IRB/IEC approved written informed consent document.
• Locally advanced stages IIIB/C or metastatic stage IV disease by American Joint Committee on Cancer (AJCC) criteria (8th edition).
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Life expectancy greater than 12 weeks.
• At least one measurable lesion per RECIST v.1.1 criteria.
• Documented HER2-negative breast cancer in the advanced setting, with any ER and PgR status. HER2-negative (immunohistochemistry (IHC) 0, 1 or IHC 2+ and negative by in situ hybridization (ISH) test) status based on local testing on the most recent analyzed biopsy.
• Prior Therapies:
• For POL6326 (balixafortide)-eribulin combination
• phase Ib: At least 1 but no more than 3 prior chemotherapy-based lines of treatment for advanced or metastatic disease.
• phase 2: At least 1 but no more than 2 prior chemotherapy-based lines of treatment for advanced or metastatic disease.
• Prior therapy should have included an anthracycline and a taxane, unless contraindicated based on investigator's criteria. Chemotherapy line given as (neo)adjuvant treatment will be considered a prior line of therapy if disease progression occurred within 12-months after completion of prior (neo)adjuvant therapy.
• Note: for phase Ib and phase 2: Disease progression after last systemic therapy documented by computerized tomography (CT) scan or magnetic resonance imaging (MRI). Exclusive tumor marker elevation will not be considered sufficient for diagnosis of disease progression.
• For POL6326 (balixafortide)-nab-paclitaxel combination
• phase Ib: At least 1 but no more than 2 prior chemotherapy-based lines of treatment for advanced or metastatic disease.

You may not qualify if:

• Patients will be excluded from the study if they meet ANY of the following criteria:
• Eribulin-based combination: patients have previously received eribulin.
• Peripheral neuropathy \> Grade 1.
• Prior radiotherapy to only site of disease.
• Patients under concurrent local radiotherapy for pain control or life-threatening situations (e.g., spinal cord compression).
• Known active uncontrolled or symptomatic CNS metastases as indicated by clinical symptoms, cerebral edema, and/or progressive growth. Patients with a history of CNS metastases are eligible if they have been definitively treated (e.g., radiotherapy, stereotactic surgery), and are clinically stable at least 4 weeks after completion of radiation therapy and/or surgery. Stable is defined as absence of new neurological symptoms, absence of need for dexamethasone or anticonvulsants, and radiographic confirmation of stable disease (SD). Radiographic confirmation of SD 4 weeks after completion of radiation therapy is not required unless indicated by neurological exam.
• Presence of carcinomatous meningitis or leptomeningeal disease.
• Therapeutic radiation therapy within 14 days (seven days for limited-field palliative radiotherapy) prior to study enrollment, or patients who have not recovered from radiotherapy-related toxicities to grade ≤ 1.
• History of allergic reactions or known hypersensitivity attributed to compounds of similar chemical or biologic composition to POL6326 (balixafortide), eribulin or nab-paclitaxel, or to recombinant proteins, or any excipient contained in the drug formulation for POL6326 (balixafortide), eribulin or nab-paclitaxel.
• Breastfeeding or pregnancy as determined by a serum pregnancy test (β-HCG) at screening, prior to the administration of POL6326 (balixafortide) and/or eribulin and/or nab-paclitaxel. Since β-HCG over expression can be also elevated in some tumor types, a positive result should be confirmed with a validated alternative test (e.g., ultrasound).
• Note: Postmenopausal women must have been amenorrhoeic for ≥ 12 months in order to be considered "of non-childbearing potential". This should be documented appropriately in the patient's medical history. More frequent assessments may be performed if medically indicated as determined by the study site Investigator, and these evaluations should be recorded in the CRF (Case Report Form).
• Known HIV positivity on combination antiretroviral therapy.
• Congenital long QT syndrome (LQTS) with corrected QT interval using the Fridericia formula (QTcF) ≥ 480 ms on baseline EKG.
• Patients under treatment with drugs known to potentially prolong the QT interval, including class Ia and III anti-arrhythmic drugs will be either monitored for corrected QT (QTc) prolongation or excluded from participation in the trial, at the discretion of the treating physician.
• Aany other concurrent severe and/or uncontrolled medical condition that would, in the Investigator's judgment contraindicate patient participation in the clinical study.

Sponsors & Collaborators

• MedSIR: lead

MeSH Terms

Interventions

balixafortide; eribulin; Taxes; Albumin-Bound Paclitaxel

Intervention Hierarchy (Ancestors)

Economics; Health Care Economics and Organizations; Paclitaxel; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Albumins; Proteins; Amino Acids, Peptides, and Proteins

Study Officials

• Javier Cortés, MD,PhD

  International Breast Cancer Center (IBCC), Quiron Group, Barcelona (Spain)

  PRINCIPAL INVESTIGATOR

• Peter Kaufman, MD

  University of Vermont Medical Center, Burlington (Vermont, USA)

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: March 25, 2021
• First Posted: April 1, 2021
• Study Start: March 16, 2022
• Primary Completion: March 16, 2022
• Study Completion: March 16, 2022
• Last Updated: March 20, 2023

Record last verified: 2023-03