First-in-Human Study of ATX-295, an Oral Inhibitor of KIF18A, as Monotherapy and in Combination With Anticancer Therapy in Patients With Advanced or Metastatic Solid Tumors, Including Ovarian Cancer

Accent Therapeutics

Status and phase: Enrolling; Phase 2; Phase 1

Conditions: sqNSCLC; Advanced Solid Tumors; High-grade Serous Ovarian Carcinoma; Squamous Non-small-cell Lung Cancer; Breast Cancer Recurrent; Triple Negative Breast Cancer; Ovarian Cancer

Treatments: Drug: ATX-295; Drug: ATX-295 and bevacizumab (or biosimilar)

Study type: Interventional

Funder types: Industry

Identifiers

NCT06799065

ATX-295-001

Details and patient eligibility

About

The goal of this study is to identify a safe and tolerated dose of the orally administered KIF18A inhibitor ATX-295. In addition, this study will evaluate the pharmacokinetics, pharmacodynamics and preliminary antitumor activity of ATX-295 as a monotherapy and in combination with bevacizumab (or a biosimilar) in patients with locally advanced or metastatic solid tumors, including ovarian cancer and lung cancer.

Full description

ATX-295 is an oral drug that inhibits a protein called KIF18A, an adenosine triphosphate (ATP)-dependent, plus end-directed mitotic kinesin. KIF18A facilitates chromosomal alignment and spindle microtubule dynamics during mitosis in certain advanced solid tumors. ATX-295 has been shown preclinically to induce robust anti-tumor activity of a variety of different solid tumors, including high-grade serious ovarian cancer, squamous non-small cell lung cancer, and triple negative breast cancer.

This is a first-in-human, Phase 1, open-label, single-arm, dose-escalation and Simon 2-Stage expansion study to evaluate the safety profile of ATX-295 and determine the recommended phase 2 dose (RP2D) as a monotherapy and in combination with bevacizumab (or a biosimilar). In addition, the study aims to characterize the PK, PD, and preliminary anti-tumor activity of orally administered ATX-295 as a monotherapy and in combination with bevacizumab (or a biosimilar). Exploratory objectives include examination of biomarker responses in relationship to ATX-295 exposure.

Patients with locally advanced or metastatic high-grade serious ovarian cancer and squamous non-small cell lung cancer will be enrolled to preliminarily assess the anti-tumor effect, and further examine the safety and PK of ATX-295 at the RP2D.

Enrollment: 218 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion Criteria:

• Patients with histologically confirmed solid tumors who have locally recurrent or metastatic disease, including HGSOC
• Refractory to or relapsed after all standard therapies with proven clinical benefit, unless as deemed by the Investigator, the subject is not a candidate for standard treatment, there is no standard treatment, or the subject refuses standard treatment after expressing an understanding of all available therapies with proven clinical benefit
• For the monotherapy expansion cohorts:
• Participants must have histological confirmation of HGSOC and be determined to be platinum-resistant, or platinum-intolerant
• Participants with sqNSCLC should have received prior treatment with a platinum, taxane, and checkpoint inhibitor
• For the combination with bevacizumab (or biosimilar): Participants must have histologically confirmed HGSOC or select solid tumors
• There is no limit to the number of prior treatment regimens
• Have measurable disease; evaluable disease is acceptable during dose escalation
• Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1

Key Exclusion Criteria:

• Clinically unstable central nervous system (CNS) tumors or brain metastasis
• Any other concurrent anti-cancer treatment, except for hormonal blockade
• Has undergone a major surgery within 3 weeks of starting study treatment
• Medical issue that limits oral ingestion or impairment of gastrointestinal function that is expected to significantly reduce the absorption of ATX-295, however participants with a functioning distal ileostomy or colostomy may be permitted on trial
• Clinically significant (ie, active) or uncontrolled cardiovascular disease
• Need to use proton pump inhibitors on study or H2-receptor antagonists for the dose escalation portion of the study.
• Unable to transition off strong or moderate CYP3A4 inhibitors or strong inducers
• Pregnancy or intent to breastfeed or conceive a child within the projected duration of treatment

Other inclusion and exclusion criteria as defined in the study protocol

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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218 participants in 4 patient groups

Dose Escalation

Experimental group

Description:

Subjects will be enrolled at various doses and/or schedules of ATX-295 to identify the expansion dose(s) and RP2D

Treatment:

Drug: ATX-295

Dose Expansion: Platinum-Resistant, or -Intolerant HGSOC

Experimental group

Treatment:

Drug: ATX-295

Dose Expansion: Previously treated sqNSCLC

Experimental group

Treatment:

Drug: ATX-295

Dose Expansion: Platinum-Resistant, or -Intolerant HGSOC and select tumors

Experimental group

Treatment:

Drug: ATX-295 and bevacizumab (or biosimilar)