Study of XL114 in Subjects With Non-Hodgkin's Lymphoma

NCT ID: NCT05144347

Last Updated: 2023-07-11

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 2 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-04-12
• Study Completion Date: 2022-11-01

Brief Summary

This is a Phase 1, non-randomized, open-label, dose-escalation and expansion study, evaluating the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary clinical antitumor activity of XL114 administered alone orally to subjects with Non-Hodgkin's Lymphoma (NHL). The objectives of the study also include determining the recommended dose (RD) and/or maximum tolerated dose (MTD) of XL114.

Conditions

Non-Hodgkin's Lymphoma (NHL); Activated B-Cell Type Diffuse Large B-Cell Lymphoma (ABC-DLBCL); Mantle Cell Lymphoma (MCL); Chronic Lymphocytic Leukemia (CLL); Small Lymphocytic Lymphoma (SLL)

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

XL114 Dose-Escalation Cohorts

Subjects (Cohort A1-An) will accrue in cohorts of 3-12 subjects in a i3+3 design.

Group Type: EXPERIMENTAL

XL114

Intervention Type: DRUG

Tablets of XL114

XL114 Expansion Cohorts

The recommended dose from the Dose-Escalation stage, will be used in subjects with activated B-cell-like diffuse large B-cell lymphoma \[ABC-DLBCL\] (Cohort B), mantle cell lymphoma \[MCL\] (Cohort C), chronic lymphocytic leukemia \[CLL\]/small lymphocytic lymphoma \[SLL\] (Cohort D). Subjects will also be enrolled in a Biomarker cohort (Cohort E).

Group Type: EXPERIMENTAL

XL114

Intervention Type: DRUG

Tablets of XL114

Interventions

XL114

Tablets of XL114

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Dose-Escalation Stage (Cohort A) and Cohort-Expansion Stage (B-E): The subject has received standard life-prolonging therapies or are not qualified to receive such therapies.

Exclusion Criteria

• Cohort-Expansion Stage Cohort B (ABC-DLBCL subtype): Subjects with histologically documented activated B-cell diffuse large B-cell lymphoma (ABC-DLBCL) subtype. Note: De novo or transformed diffuse large B-cell lymphoma (DLBCL) from previously diagnosed indolent lymphoma (eg, follicular lymphoma) is allowed.
• Cohort-Expansion Stage Cohort C (MCL): Subjects with histologically documented MCL with monoclonal B-cells that show a chromosome translocation t(11;14)(q13;q32) and/or overexpression of cyclin D1.
• Cohort-Expansion Stage Cohort D (CLL/SLL): Subjects with histologically documented CLL/SLL per the International Workshop on Chronic Lymphocytic Leukemia (iwCLL) guidelines.
• Cohort-Expansion Stage Cohort E, Biomarker Cohort (ABC-DLBCL, MCL, and SLL): Subjects with ABC-DLBCL, MCL, and SLL that fulfill the subject disease characteristics criteria as described for Cohorts B, C, or D.
• Cohort-Expansion Stage: Subjects with ABC-DLBCL, MCL, and SLL must have measurable disease by revised criteria for response assessment of lymphoma.
• Cohort-Expansion Stages: Must have archival tumor tissue available, which was collected up to 2 years prior to consent for this study. If archival tumor tissue is not available, a fresh tumor biopsy may be obtained (if safe to acquire) up to 60 days prior to first dose.
• Biomarker Cohort: Subjects must provide a fresh tumor biopsy up to 60 days prior to first dose, at week 2, day 1 (W2D1) after initiation of XL114, and at disease progression. Note: The tumor tissue requirement in the Expansion and Biomarker cohorts doesn't apply for subjects with CLL.
• Recovery to baseline or ≤ Grade 1 severity (Common Terminology Criteria for Adverse Events version 5 [CTCAE v5]) from AEs, unless AEs are clinically nonsignificant or stable.
• Left ventricular ejection fraction (LVEF) > 50% as determined by echocardiogram (ECHO) or multigated acquisition (MUGA) scan per local standard.
• Age 18 years or older on the day of consent.
• Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0-1
• Adequate organ and marrow function
• Sexually active fertile subjects and their partners must agree to highly effective methods of contraception.
• Female subjects of childbearing potential must not be pregnant at screening.

• Receipt of prior therapies as defined in the protocol
• The following lymphoma types/manifestations are not eligible for this study: Burkitt's lymphoma (BL), Burkitt-like lymphoma (BLL), lymphoblastic lymphoma/leukemia (LBL), post-transplant lymphoproliferative disease (PTLD), primary mediastinal (thymic) large B-cell lymphoma (PMBL), lymphomas involving the central nervous system (CNS) or meninges
• History of autoimmune hemolytic anemia (AIHA) or idiopathic thrombocytopenic purpura (ITP).
• History of solid organ or allogeneic hematopoietic stem cell transplantation.
• Concomitant anticoagulation with the oral anticoagulants apixaban, betrixaban, rivaroxaban, and dabigatran.
• Use of a strong inhibitor or inducer of cytochrome P450 3A4 (CYP3A4) within 5 half-lives or 4 weeks prior to first dose of study treatment, whichever is shorter.
• Uncontrolled, significant intercurrent or recent illness
• Major surgery (eg, GI surgery) within 3 weeks before first dose of study treatment.
• Corrected QT interval calculated by the Fridericia formula (QTcF) > 470 ms per electrocardiogram (ECG).
• Pregnant or lactating females.
• Inability to swallow XL114 tablets.
• Diagnosis of another malignancy within 2 years before first dose of study treatment, except for superficial skin cancers, or localized, low-grade tumors deemed cured and not treated with systemic therapy

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Exelixis

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Exelixis Clinical Site #3

Tucson, Arizona, United States

Exelixis Clinical Site #1

Indianapolis, Indiana, United States

Exelixis Clinical #4

Pittsburgh, Pennsylvania, United States

Exelixis Clinical Site #2

Spokane, Washington, United States

Countries

United States

Other Identifiers

XL114-101

Identifier Type: -

Identifier Source: org_study_id