An Early Phase Study with the Drug LOXO-305 in Patients with Previously Treated Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) or Non-Hodgkin Lymphoma (NHL)

Phase 1

• Conditions: Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) and Non-Hodgkin Lymphoma (NHL); MedDRA version: 21.0Level: LLTClassification code 10008976Term: Chronic lymphocytic leukemiaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 21.1Level: PTClassification code 10003908Term: B-cell small lymphocytic lymphomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 22.0Level: PTClassification code 10029547Term: Non-Hodgkin's lymphomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2018-003340-24-IT
• Lead Sponsor: OXO ONCOLOGY INCORPORATED

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-01-28
• Last Update Posted: 5 April 2021

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 295

Inclusion Criteria

Phase 1
1. Phase 1 dose escalation prior to PK trigger: Able to tolerate potentially subtherapeutic doses of LOXO-305 for the 28-day DLT window in the opinion of Investigator and with documented Sponsor approval
All Patients:
2. Histologically confirmed CLL/SLL or NHL failed or intolerant to standard of care therapies
3. = 2 prior lines of therapy
4. Eastern Cooperative Oncology Group (ECOG) 0-2
5. At least 18 years of age
6. Confirmation of availability of tumor sample obtained after most recent treatment as described in Protocol Section 7.4
7. Adequate hematologic status, defined as the following on C1D1 prior to treatment:
a. Absolute neutrophil count (ANC) = 0.75× 10^9/L and not requiring growth factors; if there is documented bone marrow involvement, growth factors (pegfilgastrim preferred) may be used at any time prior to C1D1 to achieve this ANC threshold
b. Platelet count = 50 × 10^9/L not requiring transfusion support; if there is documented bone marrow involvement, platelet transfusions or growth factors may be used prior to 7 days before C1D1 to achieve this platelet threshold
c. Hemoglobin (Hb) = 8 mg/dL not requiring transfusion support or growth factors; if there is documented bone marrow involvement, growth factors (e.g., epoetin alpha) may be used at any time prior to C1D1 to achieve this Hb threshold
d. Adequate coagulation, defined as activated partial thromboplastin time (aPTT) and prothrombin time (PT) (international normalized ratio [INR]) not greater than 1.5 × upper limit of normal (ULN)
8. Adequate hepatic function, defined as:
a. ALT or AST = 2.5 × the ULN or = 5 × ULN with documented liver metastases
b. Total bilirubin = 1.5 × ULN or = 3 × ULN with documented liver metastases and/or Gilbert's Disease
9. Adequate renal function defined as creatinine clearance = 30 mL/minute using Cockcroft/Gault Formula: (140 – age) × body weight (kg) × 0.85 (if female) / serum creatinine (mg/dL) × 72
10. Ability to swallow tablets and comply with outpatient treatment, laboratory monitoring, and required clinic visits for the duration of study participation
11. Willingness of men and women of reproductive potential to observe conventional and effective birth control for the duration of treatment and for 3 months following the last dose of study treatment; this may include barrier methods such as condom or diaphragm with spermicidal gel. For male subjects with a non-pregnant female partner of child-bearing potential and a woman of child-bearing potential one of the following highly effective birth control methods with a failure rate of less than 1% per year when used consistently and correctly are recommended:
a. Combined estrogen and progestin containing hormonal contraception associated with inhibition of ovulation given orally, intravaginally, or transdermally
b. Progestin-only hormonal contraception associated with inhibition of ovulation given orally, by injection, or by implant
c. Intrauterine device (IUD)
d. Intrauterine hormone-releasing system (IUS)
e. Bilateral tubal occlusion
f. Vasectomized partner
g. Sexual abstinence: considered a highly effective method only if defined as refraining from heterosexual intercourse during an entire period of risk associated with the study treatment. The reliability of sexual abstinence will be evaluated in relation to the duration of the study and to the usual lifestyle of the subject (CTFG 2014).
Birth control methods unacceptable for this clinical trial are:
a. Period

Exclusion Criteria

Phase 1 and Phase 2
All Patients:
1.Investigational agent or anticancer therapy within 5 half-lives prior to planned start of LOXO 305 except therapeutic monoclonal antibody treatment must be discontinued a minimum of 4 weeks prior to the first dose of LOXO-305. In addition, no concurrent investigational therapy is permitted.
a.Continuation of certain standard of care anticancer therapies, including hormonal therapy for breast and prostate cancer, is allowed, provided they are not on the list of prohibited concomitant medications. Refer to Section 6.3.2 for allowed and Section 6.3.3 for prohibited medications.
2.Major surgery within 4 weeks prior to planned start of LOXO 305.
3.Radiotherapy with a limited field of radiation for palliation within 7 days of the first dose of study treatment, except for patients receiving radiation to more than 30% of the bone marrow or receiving whole brain radiotherapy, which must be completed at least 4 weeks prior to the first dose of study treatment.
4.Patients requiring therapeutic anticoagulation with warfarin.
5.Any unresolved toxicities from prior therapy greater than CTCAE (version 5.0) Grade 2 at the time of starting study treatment except for alopecia.
6.History of allogeneic or autologous stem cell transplant (SCT) or chimeric antigen receptor-modified T cell (CAR-T) therapy within the past 60 days (180 days before the PK trigger) or with any of the following:
a.active graft versus host disease (GVHD);
b.cytopenias from incomplete blood cell count recovery post-transplant;
c.need for anti-cytokine therapy for toxicity from CAR-T therapy; residual symptoms of neurotoxicity > Grade 1 from CAR-T therapy;
d.ongoing immunosuppressive therapy.
7.Known central nervous system (CNS) involvement by systemic lymphoma. Patients with previous treatment for CNS involvement who are neurologically stable and without evidence of disease may be
eligible if a compelling clinical rationale is provided by the Investigator and with documented Sponsor approval
8.Active uncontrolled auto-immune cytopenia (e.g., autoimmune hemolytic anemia [AIHA], idiopathic thrombocytopenic purpura [ITP]) where new therapy introduced or concomitant therapy escalated within the 4 weeks prior to study enrollment is required to maintain adequate blood counts
9.Clinically significant, uncontrolled cardiac, cardiovascular disease or history of myocardial infarction within 6 months prior to planned start of LOXO-305, or prolongation of the QT interval corrected for heart rate (QTcF) > 470 msec on at least 2/3 consecutive electrocardiograms (ECGs), and mean QTcF > 470 msec on all 3 ECGs, during Screening. QTcF is calculated using Fridericia’s Formula (QTcF): QTcF=QT/(RR0.33).
a.Correction of suspected drug-induced QTcF prolongation can be attempted at the Investigator’s discretion and only if clinically safe to do so with either discontinuation of the offending drug or switch to another drug not known to be associated with QTcF prolongation.
10.Active uncontrolled systemic bacterial, viral, fungal or parasitic infection (except for fungal nail infection), or other clinically significant active disease process which in the opinion of the Investigator and the Sponsor makes it undesirable for the patient to participate in the trial. Screening for chronic conditions is not required.
11.Tested positive for Human Immunodeficiency Virus (HIV) is excluded (due to potential drug-drug interactions between anti-retroviral medica

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified