Phase 2
N=226
Open-label, Uncontrolled Phase II Trial of Intravenous PI3K Inhibitor BAY80-6946 in Patients With Relapsed, Indolent or Aggressive Non-Hodgkin's Lymphomas
Lymphoma, Non-Hodgkin
Bottom Line
View on ClinicalTrials.gov: NCT01660451 ↗Enrolled (actual)
226
Serious AEs
56.6%
Results posted
Jan 2018
Primary outcome: Primary: Objective Response Rate (ORR) Based on Independent Review-Part A — 43.75; 27.08 percentage of participants — p=0.0001
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Copanlisib (Aliqopa, BAY80-6946) (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Bayer
- Primary completion
- Jun 2016
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Objective Response Rate (ORR) Based on Independent Review-Part A |
43.75; 27.08 | 0.0001 sig |
| PRIMARY ORR Based on Independent Review-Part B |
59.15 | <0.0001 sig |
| PRIMARY ORR Based on Investigator Assessment-Part A |
46.88; 31.25 | 0.0001 sig |
| PRIMARY ORR Based on Investigator Assessment-Part B |
51.41 | 0.0039 sig |
| SECONDARY Duration of Response (DOR) Based on Independent Review-Part A |
322; NA | — |
| SECONDARY DOR Based on Independent Review-Part B |
14.9 | — |
| SECONDARY DOR Based on Investigator Assessment-Part A |
189; 190 | — |
| SECONDARY DOR Based on Investigator Assessment-Part B |
11.5 | — |
| SECONDARY Progression Free Survival (PFS) Based on Independent Review-Part A |
223; 70 | — |
| SECONDARY PFS Based on Independent Review-Part B |
11.3 | — |
| SECONDARY PFS Based on Investigator Assessment-Part A |
224; 70 | — |
| SECONDARY PFS Based on Investigator Assessment-Part B |
10.8 | — |
| SECONDARY Overall Survival (OS)-Part A |
657; 211 | — |
| SECONDARY OS-Part B |
59.1 | — |
| SECONDARY Functional Assessment of Cancer Therapy - Lymphoma Lymphoma Subscale (FACT-Lym LymS) at Week 16 - Part B |
46.50; 49.00 | — |
| SECONDARY Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) Total Score at Week 16 - Part B |
127.50; 130.83 | — |
Summary
The objective of the study (part A) is to evaluate the efficacy and safety of BAY80-6946 in patients with indolent or aggressive Non-Hodgkin's Lymphoma, who have progressed after standard therapy. 30 patients will be enrolled to both indolent and aggressive disease group. The objective of the study part B (CHRONOS-1) is to evaluate the efficacy and safety of BAY80-6946 in patients with relapsed/refractory follicular lymphoma. 120 patients will be enrolled in the part B of the study. Further objectives are to evaluate the pharmacokinetics and biomarkers. Quality of life will be a further objective of part B of the study.
In a cohort of 20 patients (enrolled both in part A and B) an ECG substudy will be performed to assess the potential for cardiac toxicity and QT/QTc interval prolongation of BAY80-6946.
After an up to 28-day screening period, eligible patients will start treatment with BAY80-6946 at a dose of 0.8 mg/kg (Part A) and at a dose of 60 mg (Part B).
Treatment will be continued until disease has progressed or until another criterion is met for withdrawal from study. An end-of-treatment visit will be performed within 7 days after discontinuation of study treatment. Thirty to 35 days after last study drug administration, a safety followup visit will be performed for the collection of adverse events (AEs) and concomitant medication data. Patients will be contacted quarterly to determine overall survival status up to 4 years after last patient completed treatment. Patients who discontinue study drug for reasons other than disease progression will enter the Active Assessment Follow-up period. The end of study notification to Health Authorities will be based on the completion of the collection of survival data.
The efficacy is measured by the decrease in tumor size. Tumor assessments will be done at Screening, every 8 weeks during Year 1, every 12 weeks during Year 2, and every 6 months during Year 3. Blood samples will be collected for pharmacokinetic analysis. Archival tumor tissue and blood samples will be collected for biomarker analysis (mandatory) and for central pathology review (part B), fresh biopsy tissue will also be collected if available.
Eligibility Criteria
Inclusion Criteria
- Indolent NHL:
- Histologically confirmed diagnosis of follicular lymphoma (FL) grades 1, 2 or 3a, marginal zone lymphoma (including nodal or splenic marginal zone B-cell lymphoma and mucosa-associated lymphoid tissue [MALT] lymphoma), lymphoplasmacytic lymphoma/Waldenström macroglobulinemia, chronic lymphocytic leukemia (CLL).
- Relapsed after ≥ 2 prior chemotherapy- or immunotherapy-based regimens for indolent NHL, or refractory to 2 prior chemotherapy and/ or immunotherapy-based regimens.
- Aggressive NHL:
- Histologically confirmed diagnosis of grade 3b follicular lymphoma (FL), transformed indolent lymphoma, diffuse large B-cell lymphoma (DLBCL), mediastinal large B-cell lymphoma, mantle cell lymphoma (MCL), peripheral T-cell lymphoma unspecified, or anaplastic large cell lymphoma primary systemic type, or angioimmunoblastic T cell lymphoma.
- Relapsed after ≥ 2 prior chemotherapy regimens, including the following: First-line treatment with standard anthracycline-containing regimen (e.g., cyclophosphamide, doxorubicin, vincristine, and prednisone or equivalent). At least 1 additional combination chemotherapy regimen. Patients relapsed after or refractory to first prior chemotherapy- and/or immunotherapy-based regimen for aggressive NHL and not eligible for high-dose regimen followed by transplant. High-dose chemotherapy, or chemoradiotherapy with autologous stem cell transplantation is considered 1 regimen. Patients with CD20 expressing neoplastic cells must have received prior rituximab, if available.
- Patients with transformed indolent lymphoma must have received at least 2 prior chemotherapy- and/or immunotherapy-based regimens
- Consent to provide fresh tumor tissue during screening
- Indolent B-cell NHL lymphoma (study part B):
- Histologically confirmed diagnosis of indolent B-cell NHL, with histological subtype limited to the following:
- Follicular lymphoma (FL) grade 1-2-3a
- Small lymphocytic lymphoma (SLL) with absolute lymphocyte count 18 years of age
- ECOG performance status ≤ 2 (ECOG: Eastern Cooperative Oncology Group)
- Life expectancy of at least 3 months
- Adequate bone marrow, liver and renal function as assessed within 7 days before starting study treatment
- Left ventricular ejection fraction (LVEF) ≥ lower limit of normal (LLN) for the Institution
- Availability of archival tumor tissue
Exclusion Criteria
- Uncontrolled hypertension (blood pressure ≥ 150/90 mmHg despite optimal medical management)
- Patients with evidence or history of bleeding diathesis. Any hemorrhage or bleeding event ≥ CTCAE Grade 3 within 4 weeks of start of study medication (CTCAE: Common Terminology Criteria for Adverse Events).
- History or concurrent condition of interstitial lung disease
- Unresolved toxicity higher than CTCAE grade 1 (NCI-CTC version 4.0) attributed to any prior therapy/procedure excluding alopecia. (NCI: National Cancer Institute)
- Prior treatment with PI3K inhibitors
- Systemic corticosteroid therapy (ongoing)
- Hepatitis B or C. All subjects must be screened for hepatitis B and C up to 28 days prior to study drug start using the hepatitis virus panel laboratorial routine. Subjects positive for HBsAg or HBcAb will be eligible if they are negative for HBV-DNA; subjects positive for HCV IgG will be eligible if they are negative for HCV RNA.
- For Part B:
- Histologically confirmed diagnosis of follicular lymphoma grade 3b or transformed disease and chronic lymphocytic leukemia (CLL)
- History or concurrent condition of interstitial lung disease or severely impaired pulmonary function
- Excluded medical conditions:
- Previous or concurrent cancer that is distinct in primary site or histology from indolent B-cell NHL within 5 years prior to treatment start EXCEPT for curatively treated cervical cancer in situ, nonmelanoma skin cancer and superficial bladder tumors [Ta (non-invasive tumor), Tis (carcinoma in situ) and T1 (tumor invades lamina propria)].
- Hepatitis B or C. Al
Data sourced from ClinicalTrials.gov (NCT01660451). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.