Safety, Pharmacodynamics, Pharmacokinetics, and Efficacy of GS-9901 in Adults With Relapsed or Refractory Follicular Lymphoma, Marginal Zone Lymphoma, Chronic Lymphocytic Leukemia, or Small Lymphocytic Lymphoma

Gilead Sciences

Status and phase: Terminated; Phase 1

Conditions: Marginal Zone Lymphoma; Small Lymphocytic Lymphoma; Follicular Lymphoma; Chronic Lymphocytic Leukemia

Treatments: Drug: GS-9901

Study type: Interventional

Funder types: Industry

Identifiers

NCT02258555

2014-005441-53 (EudraCT Number)

GS-US-325-1348

Details and patient eligibility

About

This study will evaluate the safety and tolerability of GS-9901 monotherapy in adults with follicular lymphoma (FL), marginal zone lymphoma (MZL), chronic lymphocytic leukemia (CLL), or small lymphocytic lymphoma (SLL). The study will also characterize the pharmacokinetic (PK) profile of GS-9901, determine the appropriate dosing regimen of GS-9901 for use in future clinical trials, and to evaluate the efficacy of GS-9901 monotherapy in adults with FL, MZL, CLL, or SLL.

Enrollment: 7 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Diagnosis of FL, MZL, SLL, or CLL (meeting International Workshop on CLL [IWCLL] Criteria, 2008) as documented by medical records and with histology based on criteria established by the World Health Organization

  • FL Grades 1, 2, or 3a
  • SLL with absolute lymphocyte count of < 5 x 10^9/L at initial diagnosis
  • MZL (splenic, nodal, or extra-nodal)

• Prior treatment for FL or CLL/SLL with ≥ 1 prior chemotherapy-based or immunotherapy-based regimen with no approved therapies available

• Presence of radiographically measurable lymphadenopathy or extra nodal lymphoid malignancy

• All acute toxic effects of any prior antitumor therapy resolved to Grade ≤1 before the start of study therapy (with the exception of alopecia [Grade 1 or 2 permitted], or bone marrow parameters [any of Grade 1, 2, or 3 permitted)

• Eastern Cooperative Oncology Group (ECOG) ≤ 2

• Able to provide written informed consent

Exclusion criteria

• History of lymphoid malignancy other than FL, MZL, SLL, or CLL
• History of myelodysplastic syndrome
• History of a non-lymphoid malignancy except for the following: adequately treated local basal cell or squamous cell carcinoma of the skin, cervical carcinoma in situ, superficial bladder cancer, asymptomatic prostate cancer without known metastatic disease and with no requirement for therapy or requiring only hormonal therapy and with normal prostate-specific antigen for ≥ 1 year prior to start of study therapy, or any other cancer that has been in complete remission for ≥ 5 years
• Evidence of ongoing systemic bacterial, fungal, or viral infection at the time of start of study therapy
• Ongoing drug-induced pneumonitis
• Ongoing inflammatory bowel disease
• History of prior allogeneic bone marrow progenitor cell or solid organ transplantation
• History of prior therapy with any inhibitor of serine/threonine kinase (AKT), Bruton tyrosine kinase (BTK), Janus kinase (JAK), mammalian target of rapamycin (mTOR), phosphatidylinositol 3-kinase (PI3K), or spleen tyrosine kinase (SYK)
• Ongoing immunosuppressive therapy, including systemic corticosteroids for treatment of lymphoid malignancy

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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7 participants in 1 patient group

GS-9901

Experimental group

Description:

Participants will receive one of 6 escalating doses of GS-9901 once daily until unacceptable toxicity, substantial noncompliance, disease progression, pregnancy, initiation of another anti-cancer or experimental therapy, or other protocol-specified reasons for GS-9901 discontinuation.

Treatment:

Drug: GS-9901