New Medicines

AliqopaRelapsed/refractory follicular B-cell non-Hodgkin lymphoma (NHL)


New molecular entity
Bayer Healthcare
Bayer Healthcare

Development and Regulatory status

Phase III Clinical Trials
Filing withdrawn
Jan 22Bayer withdraw EU filing after CHMP raised concerns about the design of the monotherapy study and robustness of the study results because of the lack of a comparator. At the time of the withdrawal, the EMA felt it was not able to draw conclusions on the effectiveness of copanlisib in treating MZL and its opinion was that the benefits in the monotherapy setting did not outweigh its risks [16].
Jan 22At present, Bayer has no plans to seek a licence for this product in the UK [15].
Jul 21Filed in EU via centralised procedure [14].
Sep 17Launched in US Q4 17 [8].
Sep 17The US approved indication is treatment of adult patients with relapsed follicular lymphoma (FL) who have received at least two prior systemic therapies, and is based on data from the CHRONOS-1 trial of copanlisib monotherapy [12].
Sep 17The US granted accelerated approval based on overall response rate. Continued approval may be contingent upon verification and description of clinical benefit in a confirmatory trial [7].
Sep 17Approved in US [6]
May 17Awarded priority review in US [5]
Jun 15PIII [3].
Apr 15Bayer Healthcare announced expansion of its global clinical development program for copanlisib (BAY 80-6946), which now includes two new Phase III studies in indolent non-Hodgkin´s lymphomas (NHL). Three new studies will open for enrolment by mid-2015 to investigate the efficacy and safety of copanlisib in pts with recurrent indolent NHL [1].


Pan-class I phosphatidylinositol-3-kinase (PI3K) inhibitor. The PI3K pathway is a frequently altered pathway in cancer and PI3K isoforms trigger cellular functions such as growth control, metabolism and transcription initiation.
The UK incidence of NHL is about 18 per 100,000 people and 40-50% have indolent (low-grade) disease, usually advanced at presentation.
Relapsed/refractory follicular B-cell non-Hodgkin lymphoma (NHL)

Trial or other data

Apr 21PIII trial CHRONOS-3 trial found improved progression-free survival (PFS) with combination of copanlisib and rituximab compared to rituximab with placebo in relapsed indolent non-Hodgkin’s Lymphoma. After a median follow-up of 19.2 months, the combination had a median PFS of 21.5 months (95% CI 17.9, 33.0) versus 13.8 months in patients treated with rituximab alone (95% CI 10.2, 17.5), (HR=0.52, p=0.000002) [13].
Dec 20PIII CHRONOS-2 trial is now due to complete collection of primary outcome data in Nov 21 [11].
Aug 20PIII CHRONOS-3 trial completes collection of primary outcome data [11].
Dec 19PIII CHRONOS-3 trial (NCT02367040) is still recruiting patients; timescales unchanged [10].
Nov 18PIII CHRONOS-3 trial (NCT02367040) is still recruiting patients; collection of primary outcome data is due to complete May 20 [9].
Nov 18PIII CHRONOS-2 trial (NCT02369016) has finished recruiting patients; collection of primary outcome data is due to complete this month [9].
Nov 16PIII CHRONOS-3 is still recruiting - collection of primary outcome data is now due to complete Jun 20 [4].
Nov 16PIII CHRONOS-2 is still recruiting - collection of primary outcome data is due to complete Mar 19 [4].
Apr 15Phase III randomized, double-blind study (CHRONOS-3) starts, evaluating the efficacy and safety of copanlisib in combination with rituximab versus rituximab monotherapy in pts with relapsed iNHL who have received one or more lines of treatment, including rituximab and alkylating agents. (NCT02367040). In CHRONOS 3, approximately 567 pts will be randomly assigned to receive either copanlisib or placebo plus rituximab administered on days 1, 8 and 15 of each 28-day cycle. The rituximab dose will be administered weekly during cycle 1 on Days 1, 8, 15 and 22, and then on Day 1 of Cycles 3, 5, 7 and 9, up to a maximum of 8 times. PFS at 51 months is the defined primary endpoint and the estimated primary completed date is October 2019 [1,2].
Apr 15CHRONOS-2: A Phase III randomized, double-blind, placebo-controlled study of copanlisib monotherapy in rituximab-refractory indolent non-Hodgkin´s lymphoma (NCT02369016) started. In CHRONOS-2, approximately 189 pts will be randomised to receive 60 mg of Copanlisib in solution or placebo administered intravenously on days 1, 8 and 15 of each 28-day treatment cycle. The primary outcome measure will be Progression Free Survival (PFS) at time points up to 29 months. It is estimated that the primary completion date will be August 2017 [1,2].
Oct 12Bayer commenced open-label, uncontrolled phase IIa trial to assess efficacy and safety of copanlisib by IV infusion in 180 pts with relapsed, indolent or aggressive non-Hodgkin´s lymphoma, who have progressed after standard therapy (CHRONOS-1; NCT01660451). Interim data from CHRONOS-1 showed that rates of overall and complete response were 40% and 20% for follicular lymphoma, 67% and 0% for chronic lymphocytic leukaemia, 83% and 17% for mantle cell lymphoma, and 50% and 0% for peripheral T-cell lymphoma, respectively. Copanlisib appeared to be generally well tolerated and 49% and 15% of pts given copanlisib and placebo experienced a grade 3 and 4 adverse event, respectively. All grade 4 adverse events were neutropenia and grade 3 hypertension and diarrhoea occurred in 31% and 5% of pts, respectively [2].

Evidence based evaluations