A Study of LOXO-783 in Patients With Breast Cancer/Other Solid Tumors

Official title

A Study of LOXO-783 Administered as Monotherapy and in Combination With Anticancer Therapies for Patients With Advanced Breast Cancer and Other Solid Tumors With a PIK3CA H1047R Mutation

Overview

The main purpose of this study is to learn more about the safety, side effects, and effectiveness of LOXO-783. LOXO-783 may be used to treat breast cancer and other solid tumors that have a change in a particular gene (known as the PIK3CA gene). Participation could last up to 36 months (3 years) and possibly longer if the disease does not get worse.

Interventions

• Drug LOXO-783
  Oral
• Drug Fulvestrant
  Intramuscular
• Drug Imlunestrant
  Oral
• Drug Abemaciclib
  Oral
• Drug Anastrozole, Exemestane, or Letrozole
  Oral
• Drug Paclitaxel
  Intravenous

Primary outcome measures

• Phase 1 a: To determine the maximum tolerated dose/recommended phase 2 dose (MTD/RP2D) of LOXO-783: Number of patients with dose-limiting toxicities (DLTs) [Time frame: During the first 28-day cycle of LOXO-783 treatment]
• Phase 1 a: To determine the MTD/RP2D of LOXO-783: Number of patients with DLT-equivalent toxicities [Time frame: During the first 28-day cycle of LOXO-783 treatment]

Secondary outcome measures (10)

• To assess the pharmacokinetics (PK) of LOXO-783: Area under the concentration versus time curve (AUC) [Time frame: Up to 2 months]
• To assess the PK of LOXO-783: Maximum drug concentration (Cmax) [Time frame: Up to 2 months]
• To evaluate the preliminary antitumor activity of LOXO-783: Overall response rate (ORR) [Time frame: Up to approximately 36 months or 3 years]
• To evaluate the preliminary antitumor activity of LOXO-783: Best overall response (BOR) [Time frame: Up to approximately 36 months or 3 years]
• To evaluate the preliminary antitumor activity of LOXO-783: Duration of response (DOR) [Time frame: Up to approximately 36 months or 3 years]
• To evaluate the preliminary antitumor activity of LOXO-783: Disease control rate (DCR) [Time frame: Up to approximately 36 months or 3 years]
• To evaluate the preliminary antitumor activity of LOXO-783: Clinical benefit rate (CBR) [Time frame: Up to approximately 36 months or 3 years]
• To evaluate the preliminary antitumor activity of LOXO-783: Time to response (TTR) [Time frame: Up to approximately 36 months or 3 years]
• To evaluate the preliminary antitumor activity of LOXO-783: Progression free survival (PFS) [Time frame: Up to approximately 36 months or 3 years]
• To evaluate the preliminary antitumor activity of LOXO-783: Overall survival (OS) [Time frame: Up to approximately 36 months or 3 years]

Eligibility criteria

Inclusion criteria

• Have advanced breast cancer or another solid tumor with the presence of a phosphatidylinositol 3-kinase catalytic subunit alpha (PIK3CA) H1047R mutation (or other Sponsor and safety review committee (SRC)-approved, activating PIK3CA mutations other than H1047R mutation)
• Have adequate archival tumor tissue sample available or be approved by the Sponsor for enrollment if no tumor sample is available.
• Have stopped all cancer treatment and have recovered from the major side effects
• Have adequate organ function, as measured by blood tests
• Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) scale
• Patients must have

• Measurable disease

\--- Patients with non-breast tumor types must have at least 1 measurable lesion

• Non-measurable bone disease (at least 1 bone lesion in breast cancer patients only)
• For patients with an estrogen receptor (ER)+ breast cancer diagnosis:

• If female, must be postmenopausal
• If male, must agree to use hormone suppression
• Phase 1a:

\-- Dose escalation and backfill patients:

• Advanced solid tumor
• Patients may have had up to 5 prior regimens for advanced disease
• Phase 1b:

• Part A:

• ER+/human epidermal growth factor receptor 2 (HER2)- advanced breast cancer
• Patients may have had up to 5 prior regimens for advanced disease ---- Prior cyclin dependent kinase (CDK)4/6 inhibitor therapy required
• Part B:

• ER+/HER2- advanced breast cancer
• Patients may have had up to 2 prior regimens for advanced disease.
• Part C:

• ER+/HER2- advanced breast cancer
• Patients may have had up to 5 prior regimens for advanced disease.

\---- Prior CDK4/6 inhibitor therapy required.

• Have a diagnosis of diabetes mellitus Type 2
• Part D:

• Advanced breast cancer
• Patients may have had up to 5 prior regimens for advanced disease.
• Part E:

• Advanced solid tumor
• Patients may have had up to 3 prior regimens for advanced disease advanced disease
• Part F:

• ER+/HER2- advanced breast cancer
• Patients may have had up to 5 prior regimens for advanced disease

• Prior cyclin dependent kinase (CDK)4/6 inhibitor therapy required

Exclusion criteria

• Medical Conditions

• Colorectal cancer
• Endometrial cancers with specific concurrent oncogenic alterations
• A history of known active or suspected

• Diabetes mellitus Type 1 or
• Diabetes mellitus Type 2 requiring antidiabetic medication (Phase 1a and all parts of Phase 1b except Part C).
• Serious concomitant systemic disorder
• Known or suspected history of untreated or uncontrolled central nervous system (CNS) involvement.
• Active uncontrolled systemic bacterial, viral, fungal, or parasitic infection, or other clinically significant active disease process
• Prior exposure to phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) inhibitor(s), except in certain circumstances

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

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 17 centers

• Mayo Clinic of Scottsdale — Scottsdale
• UCLA Medical Center — Los Angeles
• UCSF Medical Center at Mission Bay — San Francisco
• Stanford University Hospital — Stanford
• Mayo Clinic — Jacksonville
• Winship Cancer Center Emory University — Atlanta
• Massachusetts General Hospital — Boston
• Dana-Farber Cancer Institute — Boston
• … and 9 more centers

Spain · 8 centers

• Hospital Universitario Quiron Dexeus — Barcelona
• Hospital Universitari Vall d'Hebron — Barcelona
• Hospital Clinic de Barcelona — Barcelona
• Hospital General Universitario Gregorio Maranon — Madrid
• Hospital Universitario 12 de Octubre — Madrid
• Hospital Quironsalud Madrid — Pozuelo de Alarcón
• Hospital Clinico Universitario de Valencia — Valencia
• Hospital Arnau de Vilanova Valencia — Valencia

France · 5 centers

• Centre Leon Berard — Lyon
• Institut Curie — Paris
• Institut de Cancérologie de l'Ouest — Saint-Herblain
• ICANS_Institut de Cancerologie Strasbourg Europe — Strasbourg
• Gustave Roussy — Villejuif

Japan · 4 centers

• National Cancer Center Hospital — Chūōku
• The Cancer Institute Hospital of JFCR — Kōtō City
• Kyoto University Hospital — Kyoto
• Aichi Cancer Center Hospital — Nagoya

Australia · 3 centers

• Cancer Research SA — Adelaide
• Peter Maccallum Cancer Institute Erb — East Melbourne
• St Vincent's Hospital — Sydney

China · 3 centers

• Beijing Cancer hospital — Beijing
• The Third Hospital of Nanchang — Nanchang
• Fudan University Shanghai Cancer Center — Shanghai

Belgium · 2 centers

• Institut Jules Bordet — Anderlecht
• Universitaire Ziekenhuizen Leuven - Campus Gasthuisberg — Leuven

Canada · 2 centers

• Princess Margaret Hospital (Hong Kong) — Toronto
• BC Cancer Vancouver — Vancouver

South Korea · 2 centers

• Samsung Medical Center — Seoul
• Asan Medical Center — Seoul

United Kingdom · 2 centers

• Royal Marsden NHS Trust — London
• Royal Marsden Hospital (Sutton) — Sutton

Germany · 1 center

• Universitätsklinikum Erlangen — Erlangen

Singapore · 1 center

• National Cancer Centre Singapore — Singapore

Identifiers

NCT: NCT05307705 · 18394 · 2022-000175-40 · J4C-OX-JZUA · LOXO-PIK-21001

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗