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

• Status: Not yet recruiting
• Trial end date: 2025-12-11
• Target enrollment: 0
• Participant gender: All

Summary

This is a Phase 1, non-randomized, open-label, dose-escalation and expansion study, evaluating the safety, tolerability, PK, pharmacodynamics, 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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Exelixis

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.

• Dose-Escalation Stage (Cohort A): Subjects with histologically documented diagnosis of B-cell or T-cell Non-Hodgkin's Lymphoma as defined by the WHO classification. Note: Refer to exclusion criteria for lymphoma subtypes which are excluded from study participation.

• Cohort-Expansion Stage Cohort B (DLBCL-ABC subtype): Subjects with histologically documented DLBCL of activated B-cell (ABC-DLBCL) subtype. Note: De novo or transformed 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 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 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.

Exclusion Criteria:

• Receipt of prior therapies as defined in the protocol

• The following lymphoma types/manifestations are not eligible for this study: Burkitt's lymphoma, Burkitt-like lymphoma, lymphoblastic lymphoma/leukemia, 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 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