A Study of LOXO-783 in Patients With Breast Cancer/Other Solid Tumors (PIKASSO-01)

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ClinicalTrials.gov Identifier: NCT05307705

Recruitment Status : Recruiting

First Posted : April 1, 2022

Last Update Posted : March 20, 2024

See Contacts and Locations

View this study on the modernized ClinicalTrials.gov

Sponsor:

Collaborator:

Loxo Oncology, Inc.

Information provided by (Responsible Party):

Eli Lilly and Company

Tracking Information

First Submitted Date ^ICMJE

March 25, 2022

First Posted Date ^ICMJE

April 1, 2022

Last Update Posted Date

March 20, 2024

Actual Study Start Date ^ICMJE

May 11, 2022

Estimated Primary Completion Date

May 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures ^ICMJE

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 ]
Number of patients with DLTs
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 ]
Number of patients with DLT-equivalent toxicities

Original Primary Outcome Measures ^ICMJE

Phase 1 a: To determine the 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 ]
Number of patients with DLTs
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 ]
Number of patients with DLT-equivalent toxicities

Change History

Current Secondary Outcome Measures ^ICMJE

To assess the pharmacokinetics (PK) of LOXO-783: Area under the concentration versus time curve (AUC) [ Time Frame: Up to 2 months ]
PK of LOXO-783: AUC
To assess the PK of LOXO-783: Maximum drug concentration (Cmax) [ Time Frame: Up to 2 months ]
PK of LOXO-783: Cmax
To evaluate the preliminary antitumor activity of LOXO-783: Overall response rate (ORR) [ Time Frame: Up to approximately 36 months or 3 years ]
ORR per investigator assessed Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1)
To evaluate the preliminary antitumor activity of LOXO-783: Best overall response (BOR) [ Time Frame: Up to approximately 36 months or 3 years ]
BOR per investigator assessed RECIST 1.1
To evaluate the preliminary antitumor activity of LOXO-783: Duration of response (DOR) [ Time Frame: Up to approximately 36 months or 3 years ]
DOR per investigator assessed RECIST 1.1
To evaluate the preliminary antitumor activity of LOXO-783: Disease control rate (DCR) [ Time Frame: Up to approximately 36 months or 3 years ]
DCR per investigator assessed RECIST 1.1
To evaluate the preliminary antitumor activity of LOXO-783: Clinical benefit rate (CBR) [ Time Frame: Up to approximately 36 months or 3 years ]
CBR per investigator assessed RECIST 1.1
To evaluate the preliminary antitumor activity of LOXO-783: Time to response (TTR) [ Time Frame: Up to approximately 36 months or 3 years ]
TTR per investigator assessed RECIST 1.1
To evaluate the preliminary antitumor activity of LOXO-783: Progression free survival (PFS) [ Time Frame: Up to approximately 36 months or 3 years ]
PFS per investigator assessed RECIST 1.1
To evaluate the preliminary antitumor activity of LOXO-783: Overall survival (OS) [ Time Frame: Up to approximately 36 months or 3 years ]
OS per investigator assessed RECIST 1.1

Original Secondary Outcome Measures ^ICMJE

To assess the pharmacokinetics (PK) of LOXO-783: Area under the concentration versus time curve (AUC) [ Time Frame: Up to 2 months ]
PK of LOXO-783: AUC
To assess the PK of LOXO-783: Maximum drug concentration (Cmax) [ Time Frame: Up to 2 months ]
PK of LOXO-783: Cmax
To evaluate the preliminary antitumor activity of LOXO-783: Overall response rate (ORR) [ Time Frame: Up to approximately 36 months or 3 years ]
ORR per investigator assessed RECIST 1.1
To evaluate the preliminary antitumor activity of LOXO-783: Best overall response (BOR) [ Time Frame: Up to approximately 36 months or 3 years ]
BOR per investigator assessed RECIST 1.1
To evaluate the preliminary antitumor activity of LOXO-783: Duration of response (DOR) [ Time Frame: Up to approximately 36 months or 3 years ]
DOR per investigator assessed RECIST 1.1
To evaluate the preliminary antitumor activity of LOXO-783: Disease control rate (DCR) [ Time Frame: Up to approximately 36 months or 3 years ]
DCR per investigator assessed RECIST 1.1
To evaluate the preliminary antitumor activity of LOXO-783: Clinical benefit rate (CBR) [ Time Frame: Up to approximately 36 months or 3 years ]
CBR per investigator assessed RECIST 1.1
To evaluate the preliminary antitumor activity of LOXO-783: Time to response (TTR) [ Time Frame: Up to approximately 36 months or 3 years ]
TTR per investigator assessed RECIST 1.1
To evaluate the preliminary antitumor activity of LOXO-783: Progression free survival (PFS) [ Time Frame: Up to approximately 36 months or 3 years ]
PFS per investigator assessed RECIST 1.1
To evaluate the preliminary antitumor activity of LOXO-783: Overall survival (OS) [ Time Frame: Up to approximately 36 months or 3 years ]
OS per investigator assessed RECIST 1.1

Current Other Pre-specified Outcome Measures

Not Provided

Original Other Pre-specified Outcome Measures

Not Provided

Descriptive Information

Brief Title ^ICMJE

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

Official Title ^ICMJE

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

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.

Detailed Description

Not Provided

Study Type ^ICMJE

Interventional

Study Phase ^ICMJE

Phase 1

Study Design ^ICMJE

Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment

Condition ^ICMJE

Breast Cancer

Intervention ^ICMJE

Drug: LOXO-783
Oral

Other Name: LY3849524
Drug: Fulvestrant
Intramuscular
Drug: Imlunestrant
Oral

Other Name: LY3484356
Drug: Abemaciclib
Oral

Other Name: LY2835219
Drug: Anastrozole, Exemestane, or Letrozole
Oral
Drug: Paclitaxel
Intravenous

Study Arms ^ICMJE

Experimental: Phase 1A: LOXO-783 Monotherapy Dose Escalation
LOXO-783 administered orally

Intervention: Drug: LOXO-783
Experimental: Phase 1B: Part A
LOXO-783 administered orally in combination with fulvestrant intramuscularly, imlunestrant orally, or an aromatase inhibitor orally
Interventions:
- Drug: LOXO-783
- Drug: Fulvestrant
- Drug: Imlunestrant
- Drug: Anastrozole, Exemestane, or Letrozole
Experimental: Phase 1B: Part B
LOXO-783 orally in combination with abemaciclib and either physician's choice aromatase inhibitor orally, fulvestrant intramuscularly, or imlunestrant orally
Interventions:
- Drug: LOXO-783
- Drug: Fulvestrant
- Drug: Imlunestrant
- Drug: Abemaciclib
- Drug: Anastrozole, Exemestane, or Letrozole
Experimental: Phase 1B: Part C
LOXO-783 orally in combination with fulvestrant intramuscularly
Interventions:
- Drug: LOXO-783
- Drug: Fulvestrant
Experimental: Phase 1B: Part D
LOXO-783 orally in combination with paclitaxel intravenously
Interventions:
- Drug: LOXO-783
- Drug: Paclitaxel
Experimental: Phase 1B: Part E
LOXO-783 orally

Intervention: Drug: LOXO-783
Experimental: Phase 1B: Part F
Multiple randomized dose levels of LOXO-783 orally with fulvestrant intramuscularly
Interventions:
- Drug: LOXO-783
- Drug: Fulvestrant

Publications *

Not Provided

* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.

Recruitment Information

Recruitment Status ^ICMJE

Recruiting

Estimated Enrollment ^ICMJE

400

Original Estimated Enrollment ^ICMJE

260

Estimated Study Completion Date ^ICMJE

May 2025

Estimated Primary Completion Date

May 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria ^ICMJE

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

Sex/Gender ^ICMJE

Sexes Eligible for Study:

All

Ages ^ICMJE

18 Years and older (Adult, Older Adult)

Accepts Healthy Volunteers ^ICMJE

Contacts ^ICMJE

Contact: Patient Advocacy

855-569-6305

clinicaltrials@loxooncology.com;

Listed Location Countries ^ICMJE

Australia, Belgium, Canada, China, France, Germany, Italy, Japan, Korea, Republic of, Singapore, Spain, United Kingdom, United States

Removed Location Countries

Administrative Information

NCT Number ^ICMJE

NCT05307705

Other Study ID Numbers ^ICMJE

LOXO-PIK-21001
J4C-OX-JZUA ( Other Identifier: Eli Lilly and Company )
2022-000175-40 ( EudraCT Number )

Has Data Monitoring Committee

U.S. FDA-regulated Product

Studies a U.S. FDA-regulated Drug Product:	Yes
Studies a U.S. FDA-regulated Device Product:	No

IPD Sharing Statement ^ICMJE

Plan to Share IPD:

Current Responsible Party

Eli Lilly and Company

Original Responsible Party

Same as current

Current Study Sponsor ^ICMJE

Eli Lilly and Company

Original Study Sponsor ^ICMJE

Same as current

Collaborators ^ICMJE

Loxo Oncology, Inc.

Investigators ^ICMJE

Study Director:

Vincent Chau, MD; PhD

Loxo Oncology, Inc.

PRS Account

Eli Lilly and Company

Verification Date

March 2024

^ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

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