Nordic Nanovector to amend PARADIGME trial protocol to expand eligible patient population

Nordic Nanovector ASA (OSE: NANO) announces that it will amend the trial protocol for its PARADIGME trial to broaden the inclusion criteria and expand the pool of eligible patients with the aim of increasing the present rate of enrolment. This decision has been made based on the company’s reviewed discussions with the US Food and Drug Administration (FDA).

PARADIGME is the company’s ongoing pivotal, global, randomised Phase 2b trial investigating Betalutin® (¹⁷⁷Lu-lilotomab satetraxetan) as a single administration in 3^rd-line relapsed/refractory follicular lymphoma (3L R/R FL) patients. The trial aims to enrol 130 patients into two arms to compare different dosing regimens; 51 patients were enrolled as of 25^th May 2020 - Q1 report.

One of the measures to improve the recruitment rate into PARADIGME is to allow for FL patients who have undergone stem cell transplant (SCT) to be included in the trial. In some countries, for example UK, Italy, Turkey, Israel and Spain, SCT is frequently used for treating R/R FL and patients who have had a SCT make up the majority of 3L FL patients. This and other ways to broaden the inclusion criteria will, when implemented, substantially expand the pool of patients eligible for recruitment into PARADIGME.

As soon as practicable, Nordic Nanovector will seek approvals for the protocol amendments from the regulators in each of the 25 countries in which PARADIGME is active. It is anticipated that it will take 2-3 months to gain approval for these protocol amendments in all countries. Until the amendments have been approved, the company will continue to enrol patients under the existing protocol.

A close collaboration with the company’s Clinical Research Organisation (CRO) will be prioritised to ensure smooth implementation of the new protocol and maximise enrolment once the new protocol is approved in each country.

The company expects that expanding the pool of eligible patients will significantly improve the present enrolment rate. During August, the company will provide updated timelines for PARADIGME based on more clarity on the impact of COVID-19 and after the completion of the interim analysis.

In the Phase 1/2 LYMRIT 37-01 study, a single administration of Betalutin® demonstrated encouraging anti-tumour activity, with a 65%, overall response rate (ORR) and 28% complete responses (CR) in the subset of FL patients (n=57). The median duration of response (mDoR) was over one year (13.6 months) for all responders and nearly three years (32.0 months) for complete responders. 

The LYMRIT 37-01 study also showed that Betalutin® was safe and well tolerated in these fragile patients with advanced stage disease, who have few remaining options available.

Jean Pierre Bizzari, MD, Chair of Nordic Nanovector’s Clinical Committee, said: “We are extremely encouraged by the preliminary data we are seeing both in terms of efficacy and safety profile. This novel ’one-time‘ treatment in this underserved resistant/refractory patient population is especially important in these frail elderly patients for whom other treatment options are too toxic. We are confident that the protocol amendments the company is implementing to expand the eligible pool of FL patients will significantly increase the rate of enrolment into PARADIGME.”

Dominic Smethurst, MD, interim Chief Medical Officer, commented: “We are very happy that we can now start to implement these important protocol amendments to PARADIGME. As soon as the amendments are made, we will implement a plan with our CRO to gain approval in all currently active countries as soon as possible. We intend to provide an updated timeline for PARADIGME once we have more clarity on the impact of the easing of the COVID-19 restrictions and the completion of the interim analysis.”

“We are also very pleased to have received Fast Track designation for Betalutin® in marginal zone lymphoma (MZL), another form of non-Hodgkin’s lymphoma for which new treatments are urgently needed and against which Betalutin® has already demonstrated encouraging data. We are evaluating this new opportunity within the context of PARADIGME and will provide an update when we have made a decision on our development plans in this indication.”