Clinical trial NCT05307705: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Breast Cancer
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2022-04-01
Enrollment: 193
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: 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.


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

Primary outcomes:
measure: 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)
timeFrame: During the first 28-day cycle of LOXO-783 treatment
measure: Phase 1 a: To determine the MTD/RP2D of LOXO-783: Number of patients with DLT-equivalent toxicities
timeFrame: During the first 28-day cycle of LOXO-783 treatment
Secondary outcomes:
measure: To assess the pharmacokinetics (PK) of LOXO-783: Area under the concentration versus time curve (AUC)
timeFrame: Up to 2 months
measure: To assess the PK of LOXO-783: Maximum drug concentration (Cmax)
timeFrame: Up to 2 months
measure: To evaluate the preliminary antitumor activity of LOXO-783: Overall response rate (ORR)
timeFrame: Up to approximately 36 months or 3 years
measure: To evaluate the preliminary antitumor activity of LOXO-783: Best overall response (BOR)
timeFrame: Up to approximately 36 months or 3 years
measure: To evaluate the preliminary antitumor activity of LOXO-783: Duration of response (DOR)
timeFrame: Up to approximately 36 months or 3 years
measure: To evaluate the preliminary antitumor activity of LOXO-783: Disease control rate (DCR)
timeFrame: Up to approximately 36 months or 3 years
measure: To evaluate the preliminary antitumor activity of LOXO-783: Clinical benefit rate (CBR)
timeFrame: Up to approximately 36 months or 3 years
measure: To evaluate the preliminary antitumor activity of LOXO-783: Time to response (TTR)
timeFrame: Up to approximately 36 months or 3 years
measure: To evaluate the preliminary antitumor activity of LOXO-783: Progression free survival (PFS)
timeFrame: Up to approximately 36 months or 3 years
measure: To evaluate the preliminary antitumor activity of LOXO-783: Overall survival (OS)
timeFrame: Up to approximately 36 months or 3 years
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Mayo Clinic of Scottsdale
state: Arizona
city: Los Angeles
country: United States
facility: UCLA Medical Center
state: California
city: San Francisco
country: United States
facility: UCSF Medical Center at Mission Bay
state: California
city: Stanford
country: United States
facility: Stanford University Hospital
state: California
city: Jacksonville
country: United States
facility: Mayo Clinic
state: Florida
city: Atlanta
country: United States
facility: Winship Cancer Center Emory University
state: Georgia
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University Medical School
state: Missouri
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Rochester
country: United States
facility: Wilmot Cancer Institute
state: New York
city: Nashville
country: United States
facility: Tennessee Oncology PLLC
state: Tennessee
city: Dallas
country: United States
facility: Texas Oncology-Baylor Charles A. Sammons Cancer Center
state: Texas
city: Dallas
country: United States
facility: UT Southwestern Medical Center
state: Texas
city: Houston
country: United States
facility: University of Texas MD Anderson Cancer Center
state: Texas
city: San Antonio
country: United States
facility: South Texas Accelerated Research Therapeutics (START)
state: Texas
city: Sydney
country: Australia
facility: St Vincent's Hospital
state: New South Wales
city: East Melbourne
country: Australia
facility: Peter Maccallum Cancer Institute Erb
state: Victoria
city: Adelaide
country: Australia
facility: Cancer Research SA
city: Anderlecht
country: Belgium
facility: Institut Jules Bordet
state: Bruxelles-Capitale, Région De
city: Leuven
country: Belgium
facility: Universitaire Ziekenhuizen Leuven - Campus Gasthuisberg
city: Vancouver
country: Canada
facility: BC Cancer Vancouver
state: British Columbia
city: Toronto
country: Canada
facility: Princess Margaret Hospital (Hong Kong)
state: Ontario
city: Beijing
country: China
facility: Beijing Cancer hospital
state: Beijing
city: Nanchang
country: China
facility: The Third Hospital of Nanchang
state: Jiangxi
city: Changsha
country: China
facility: Hunan Cancer Hospital
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
city: Lyon CEDEX 08
country: France
facility: Centre Leon Berard
state: Alpes
city: Saint Herblain
country: France
facility: Institut de Cancérologie de l'Ouest
state: Loire-Atlantique
city: Caen Cedex 5
country: France
facility: Centre François Baclesse
city: Paris
country: France
facility: Institut Curie
city: Strasbourg
country: France
facility: ICANS_Institut de Cancerologie Strasbourg Europe
city: Villejuif
country: France
facility: Gustave Roussy
city: Erlangen
country: Germany
facility: Universitätsklinikum Erlangen
state: Bayern
city: Frankfurt am Main
country: Germany
facility: Klinikum der Johann Wolfgang Goethe-Universität Frankfurt
state: Hessen
city: Tübingen
country: Germany
facility: Universitaetsklinikum Tuebingen
state: Württemberg
city: Milano
country: Italy
facility: Istituto Europeo di Oncologia IRCCS
city: Nagoya
country: Japan
facility: Aichi Cancer Center Hospital
state: Aichi
city: Chuo-ku
country: Japan
facility: National Cancer Center Hospital
state: Tokyo
city: Koto City
country: Japan
facility: The Cancer Institute Hospital of JFCR
state: Tokyo
city: Kyoto
country: Japan
facility: Kyoto University Hospital
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
state: Korea
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
state: Teukbyeolsi [Seoul]
city: Singapore
country: Singapore
facility: National Cancer Centre Singapore
state: Central Singapore
city: Pozuelo de Alarcon
country: Spain
facility: Hospital Quironsalud Madrid
state: Madrid, Comunidad De
city: València
country: Spain
facility: Hospital Clinico Universitario de Valencia
state: Valenciana, Comunitat
city: Barcelona
country: Spain
facility: Hospital Universitario Quiron Dexeus
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Maranon
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Valencia
country: Spain
facility: Hospital Arnau de Vilanova Valencia
city: London
country: United Kingdom
facility: Royal Marsden NHS Trust
state: Greater London
city: Sutton
country: United Kingdom
facility: Royal Marsden Hospital (Sutton)
state: Surrey
Study officials:
affiliation: Eli Lilly and Company
name: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)
role: STUDY_DIRECTOR
References: