First-in-Human Study of STX-478 as Monotherapy and in Combination With Other Antineoplastic Agents in Participants With Advanced Solid Tumors (PIKALO-1)

Lilly

Status and phase: Enrolling; Phase 2; Phase 1

Conditions: Breast Cancer; Solid Tumors, Adult

Treatments: Drug: Exemestane; Drug: Letrozole; Drug: Fulvestrant; Drug: Ribociclib; Drug: Anastrozole; Drug: Palbociclib; Drug: STX-478

Study type: Interventional

Funder types: Industry

Identifiers

NCT05768139

27691

2023-000442-41 (EudraCT Number)

STX-478-101

2023-504807-94-00 (Other Identifier)

J6M-OX-JSGA (Other Identifier)

Details and patient eligibility

About

Study STX-478-101 (LY4064809) is a multipart, open-label, phase 1/2 study evaluating the safety, tolerability, pharmacokinetics (PK), and preliminary antitumor activity of STX-478 (LY4064809) in participants with advanced solid tumors with P13Ka mutations.

Part 1 will evaluate STX-478 as monotherapy in participants with advanced solid tumors. Part 2 will evaluate STX-478 therapy as combination therapy with fulvestrant in participants with hormone receptor positive (HR+) breast cancer. Part 3 will evaluate STX-478 as combination therapy with endocrine therapy (aromatase inhibitors, fulvestrant or imlunestrant) and a CDK4/6 Inhibitor (either Ribociclib, Palbociclib or Abemaciclib) in participants with HR+ breast cancer.

Each study part will include a 28-day screening period, followed by treatment with STX-478 monotherapy or combination therapy.

Enrollment: 720 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion Criteria:

• Has an advanced or refractory solid tumor malignancy that is metastatic or locally advanced and unresectable (as specified by Cohort)
• Has a new or recent tumor biopsy (collected at screening, if feasible) or will provide an adequate tissue sample prior to screening
• Has a tumor that harbors a documented PI3Kα mutation (cohort specific criterion for cohort-specific mutation types)
• Is ≥18 years of age at the time of signing the ICF
• Has an ECOG performance status score of 0 or 1 at screening
• Has adequate organ function as defined per protocol

Key Exclusion Criteria:

• Has history (within ≤2 years before screening) of a solid tumor or hematological malignancy that is histologically distinct from the cancers being studied
• Has symptomatic brain or spinal metastases
• Has an established diagnosis of uncontrolled diabetes mellitus (defined as HbA1c ≥8% and/or FBG ≥140 mg/dL [7.7 mmol/L] and/or requiring or required insulin).
• Has had prior treatment with PI3K/AKT/mTOR inhibitor(s), except in certain circumstances
• Has had treatment with any local or systemic antineoplastic therapy or investigational anticancer agent within 14 days or 4 half-lives, whichever is longer, prior to the initiation of study treatment up to a maximum washout period of 28 days. Endocrine therapy does not require a washout period if the patient is enrolling in a cohort with the same combination endocrine therapy.
• Has toxicities from previous anticancer therapies that have not resolved to baseline levels or CTCAE grade ≤1, with the exception of alopecia and peripheral neuropathy.
• Has had radiotherapy within 14 days before the initiation of study treatment

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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720 participants in 4 patient groups

Dose Escalation (Advanced Solid Tumors)

Experimental group

Description:

* Cohort A0: Advanced Solid tumors expressing PI3Kα mutations * Cohort A1: HR+ breast cancer expressing PI3Kα mutations

Treatment:

Drug: STX-478

Dose Expansion

Experimental group

Description:

* Cohort A1: HR+/HER2- breast cancer expressing PI3Ka mutations * Cohort A2: Gynecologic cancers * Cohort A3: Head and Neck Squamous Cell Carcinoma * Cohorts A4/A5: Other solid tumors not included in Cohorts A1, A2, or A3 expressing PI3Kα mutations * Cohort A6: Endometrial cancer

Treatment:

Drug: STX-478

Dose Selection/Expansion: Combination STX-478 + fulvestrant

Experimental group

Description:

Cohort B: HR+/HER2- or HR+/HER2low breast cancer expressing PI3Kα mutations

Treatment:

Drug: STX-478

Drug: Fulvestrant

Dose Selection/Expansion Combination

Experimental group

Description:

STX-478 + Endocrine therapy + CDK4/6 inhibitor Cohort C/D/E: HR+/HER2- or HR+/HER2low breast cancer expressing PI3Ka mutations

Treatment:

Drug: STX-478

Drug: Palbociclib

Drug: Anastrozole

Drug: Ribociclib

Drug: Letrozole

Drug: Fulvestrant

Drug: Exemestane