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: 20.1 Level: LLT Classification code 10008976 Term: Chronic lymphocytic leukemia System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 20.0 Level: PT Classification code 10003908 Term: B-cell small lymphocytic lymphoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 20.0 Level: PT Classification code 10029547 Term: Non-Hodgkin's lymphoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2018-003340-24-FR
• Lead Sponsor: oxo Oncology, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2019-06-24
• Last Update Posted: 25 November 2019

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: Not specified
• Target Recruitment: 190

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. Vasec

Exclusion Criteria

Phase 1 and Phase 2
All Patients:
1. Transformation (e.g., Richter’s transformation, prolymphocytic leukemia, transformed NHL, blastoid lymphoma) prior to planned start of LOXO-305
2. Investigational agent or anticancer therapy within 2 weeks prior to planned start of LOXO-305. In addition, no concurrent investigational therapy is permitted.
a. Continuation of certain standard of care anticancer therapies, including hormonal therapy for localized breast and prostate cancer, is allowed, provided they are not on the list of prohibited concomitant medications. Refer to Protocol Section 6.3.2 for allowed and Section 6.3.3 for prohibited medications.
b. Therapeutic monoclonal antibody treatment must be discontinued a minimum of 4 weeks prior to the first dose of LOXO-305
c. LOXO-305 may be started sooner after prior investigational agent or anticancer therapy if considered by the Investigator to be safe and within the best interest of the patient (e.g., to avoid disease flare) and with documented Sponsor approval.
3. Major surgery within 4 weeks prior to planned start of LOXO-305
4. 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
5. Patients requiring therapeutic anticoagulation
6. Any unresolved toxicities from prior therapy greater than CTCAE (version 5.0) Grade 2 at the time of starting study treatment except for alopecia
7. History of allogeneic or autologous stem cell transplant (SCT) or CAR-T therapy within the last 100 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
8. Known central nervous system (CNS) involvement by 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
9. Active uncontrolled auto-immune cytopenia (e.g., autoimmune hemolytic anemia [AIHA], idiopathic thrombocytopenic purpura [ITP])
10. 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/(RR^0.33).
a. Correction of suspected drug-induced QTcF prolongation can be attempted at the Investigator’s discretion and only if clinically safe to do so.
11. Active uncontrolled systemic bacterial, viral, fungal or parasitic infection (

Study & Design

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