ASPEN-09-03: A Study of Evorpacept in Combination With Trastuzumab and Chemotherapy in Metastatic HER2-Positive Breast Cancer

Official title

Protocol ASPEN-09-03: A Single-arm Phase 2 Multicenter Study of Evorpacept in Combination With Trastuzumab and Chemotherapy in Participants With Metastatic HER2-Positive Breast Cancer, a Substudy Under Master Protocol ASPEN-09: A Phase 1b/2, Multicenter, Multi Arm Study of Evorpacept in Combination With Anti-cancer Therapies in Advanced / Metastatic Malignancies

Overview

The Substudy Protocol ASPEN-09-03 is a Phase 2, single-arm, multicenter study evaluating the efficacy, safety, and tolerability of evorpacept in combination with trastuzumab and chemotherapy in participants with HER2-positive metastatic breast cancer who have previously received trastuzumab-deruxtecan. This substudy is actively recruiting. ASPEN-09-03 is a substudy under Master Protocol ASPEN-09, and additional substudies are as follows: * Metastatic colorectal cancer (CRC) - dose escalation phase to evaluate evorpacept in combination with other drugs. This substudy is not open. * Recurrent/metastatic head and neck cancer (HNSCC) - dose escalation phase to evaluate evorpacept in combination with other drugs. This substudy is not open.

Detailed description

Participants will continue study treatment until disease progression, death, unacceptable toxicity, participant request to stop treatment, investigator decision or study termination by the sponsor.

As ASPEN-09-03 (MBC) is the only substudy open under ASPEN-09, the information reflected in the enrollment number, arms/interventions, outcome measures, and eligibility criteria currently includes only MBC.

Interventions

• Drug Evorpacept (ALX148)
  IV infusion
• Drug Trastuzumab
  IV infusion
• Drug Paclitaxel
  IV infusion
• Drug Capecitabine
  Oral administration
• Drug Eribulin
  IV infusion
• Drug Gemcitabine
  IV infusion
• Drug Vinorelbine
  IV infusion

Primary outcome measures

• Overall Response Rate (ORR) using RECIST v1.1 based on BICR assessment [Time frame: Approximately 6 months after the last participant is enrolled]

Secondary outcome measures (12)

• Overall Response Rate (ORR) based on Investigator assessment [Time frame: Approximately 6 months after the last participant is enrolled]
• Clinical Benefit Rate (CBR) using RECIST v1.1 based on BICR and Investigator assessment [Time frame: Approximately 6 months after the last participant is enrolled]
• Duration of Response (DoR) using RECIST v1.1 based on BICR and Investigator assessment [Time frame: Approximately 6 months after the last participant is enrolled]
• Progression-Free Survival (PFS) using RECIST v1.1 based on BICR and Investigator assessment [Time frame: Approximately 6 months after the last participant is enrolled]
• Overall Survival (OS) [Time frame: Approximately 6 months after the last participant is enrolled]
• Number of participants with adverse events (AEs) and with laboratory abnormalities [Time frame: Enrollment to 28 days after the last administration of the study drug]
• Maximum Concentration (Cmax) [Time frame: Approximately 6 months after the last participant is enrolled]
• Time at Maximum Concentration (Tmax) [Time frame: Approximately 6 months after the last participant is enrolled]
• Area under the Concentration-Time Curve (AUC) [Time frame: Approximately 6 months after the last participant is enrolled]
• Clearance (CL) [Time frame: Approximately 6 months after the last participant is enrolled]
• Terminal elimination half-life (t1/2) [Time frame: Approximately 6 months after the last participant is enrolled]
• Evaluate the immunogenicity of evorpacept [Time frame: Approximately 6 months after the last participant is enrolled]

Eligibility criteria

Inclusion criteria

• Histologically confirmed invasive HER2+ breast cancer.
• Received at least one prior line of therapy including T-DXd (ENHERTU) for locally advanced/metastatic HER2+ breast cancer. Prior neoadjuvant therapy which resulted in relapse within 6 months of completion of T-DXd will be considered a line of treatment for metastatic disease. Participants who discontinue T-DXd due to intolerance are considered eligible.
• Progressed on or following the most recent line of therapy.
• Eligible to receive one of the following chemotherapy options (capecitabine, eribulin, gemcitabine, paclitaxel or vinorelbine).
• Measurable disease as defined by RECIST v1.1.
• LVEF ≥50%.
• Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) must be 0 to 1.
• Life expectancy of at least 3 months.
• Adequate renal function (estimated creatinine clearance ≥30 mL/min as calculated using the Cockcroft-Gault equation or Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation.
• Adequate liver function:

• Total bilirubin ≤1.5 x upper limit of normal (ULN) (≤3.0 x ULN if the participant has documented Gilbert syndrome);
• Aspartate and alanine transaminase (AST and ALT) ≤3 x ULN (≤5.0 x ULN if liver involved by metastatic disease).
• Participants must have recovered from all AEs due to previous therapies, procedures, and surgeries to baseline severity or ≤Grade 1 per NCI CTCAE v5.0 except for AEs not deemed reversible and which do not constitute a safety risk by Investigator judgment.

Exclusion criteria

• Participants with known CNS metastases unless treated and stable prior to enrollment.
• Prior exposure to any anti-CD47 or anti-SIRPα agent.
• Any condition that would be contraindicated to receiving trastuzumab
• Has a diagnosis of complete dihydropyrimidine dehydrogenase (DPD) deficiency or significant toxicity with prior flurouracil (5FU) based regimen
• Following anti-cancer therapy with insufficient washout before start of treatment:

• chemotherapy, hormonal therapy, radiation therapy or small molecule anti-cancer therapy within 14 days or 5 half-lives (whichever is shorter) of start of treatment.
• Immune therapy or other biologic therapy (e.g., monoclonal antibodies, antibody-drug conjugates) for the treatment of cancer for: 28 days or 5 half-lives (whichever is shorter) of start of treatment).
• History of autoimmune hemolytic anemia, autoimmune thrombocytopenia, or hemolytic transfusion reaction.
• Had an allogeneic tissue/solid organ transplant.
• Any active, unstable cardiovascular disease.
• Intolerance to or who have had a severe allergic or anaphylactic reaction to antibodies or infused therapeutic proteins or participants who have had a severe allergic or anaphylactic reaction to any of the substances included in the study drug (including excipients).
• Has an active autoimmune disease that has required systemic treatment in past 2 years.
• Other primary malignancy within 2 years.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 21 centers

• The University of Arizona Cancer Center - North Campus — Tucson
• City of Hope — Duarte
• UC San Diego Moores Cancer Center — La Jolla
• UC Irvine Health - Chao Family Comprehensive Cancer Center — Orange
• Saint Joseph Hospital - Cancer Centers of Colorado — Denver
• Lutheran Hospital - Cancer Centers of Colorado — Golden
• Saint Mary's Regional Hospital - Cancer Centers of Colorado — Grand Junction
• The George Washington Medical facility Associates — Washington D.C.
• … and 13 more centers

South Korea · 6 centers

• Inha University Hospital — Incheon
• Seoul National University Hospital — Seoul
• Severance Hospital, Yonsei University Health System — Seoul
• Asan Medical Center — Seoul
• Samsung Medical Center — Seoul
• Korea University Guro Hospital — Seoul

Spain · 5 centers

• Hospital Universitario Virgen de la Victoria — Málaga
• Hospital Universitario Virgen Macarena — Seville
• Hospital Universitari Arnau de Villanova — Lleida
• Hospital de la Santa Creu i Sant Pau — Barcelona
• Hospital Beata Maria Ana — Madrid

France · 4 centers

• Hopital de l'Institut Curie — Paris
• Hopital Europeen Georges Pompidou (HEGP) — Paris
• Centre Hospitalier Universitaire (CHU) de Poitiers — Poitiers
• Centre Eugene Marquis — Rennes

Italy · 3 centers

• Azienda Ospedaliero Universitaria delle Marche — Torrette
• IRCCS Azienda Ospedaliera Metropolitana — Genova
• Azienda Ospedaliero- Universitaria Maggiore della CaritÃ, SCDU Oncologia — Novara

Singapore · 2 centers

• National Cancer Centre Singapore — Singapore
• Curie Oncology - Farrer — Singapore

United Kingdom · 2 centers

• Barts Health NHS Trust - St Bartholomew's Hospital — London
• Velindre Cancer Centre, Velindre University NHS Trust — Cardiff

Canada · 1 center

• University Health Network, Princess Margaret Cancer Centre — Toronto

Identifiers

NCT: NCT07007559 · AT148009

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗