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

Lilly

Status and phase: Active, not recruiting; Phase 1

Conditions: Breast Cancer

Treatments: Drug: Anastrozole, Exemestane, or Letrozole; Drug: Paclitaxel; Drug: Fulvestrant; Drug: LOXO-783; Drug: Abemaciclib; Drug: Imlunestrant

Study type: Interventional

Funder types: Industry

Identifiers

NCT05307705

LOXO-PIK-21001

18394

2022-000175-40 (EudraCT Number)

J4C-OX-JZUA (Other Identifier)

Details and patient eligibility

About

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.

Enrollment: 193 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

---

193 participants in 7 patient groups

Phase 1A: LOXO-783 Monotherapy Dose Escalation

Experimental group

Description:

LOXO-783 administered orally

Treatment:

Drug: LOXO-783

Phase 1B: Part A

Experimental group

Description:

LOXO-783 administered orally in combination with fulvestrant intramuscularly, imlunestrant orally, or an aromatase inhibitor orally

Treatment:

Drug: Imlunestrant

Drug: LOXO-783

Drug: Fulvestrant

Drug: Anastrozole, Exemestane, or Letrozole

Phase 1B: Part B

Experimental group

Description:

LOXO-783 orally in combination with abemaciclib and either physician's choice aromatase inhibitor orally, fulvestrant intramuscularly, or imlunestrant orally

Treatment:

Drug: Imlunestrant

Drug: Abemaciclib

Drug: LOXO-783

Drug: Fulvestrant

Drug: Anastrozole, Exemestane, or Letrozole

Phase 1B: Part C

Experimental group

Description:

LOXO-783 orally in combination with fulvestrant intramuscularly

Treatment:

Drug: LOXO-783

Drug: Fulvestrant

Phase 1B: Part D

Experimental group

Description:

LOXO-783 orally in combination with paclitaxel intravenously

Treatment:

Drug: LOXO-783

Drug: Paclitaxel

Phase 1B: Part E

Experimental group

Description:

LOXO-783 orally

Treatment:

Drug: LOXO-783

Phase 1B: Part F

Experimental group

Description:

Multiple randomized dose levels of LOXO-783 orally with fulvestrant intramuscularly

Treatment:

Drug: LOXO-783

Drug: Fulvestrant