Clinical Trials

Date: 2017-05-19

Type of information: update on patient enrollment

phase: 1-2

Announcement: update on patient enrollment

Company: Nordic Nanovector (Norway)

Product: Betalutin™ (177Lu-Dota-tetulomab)

Action mechanism: radiopharmaceutical/monoclonal antibody. Betalutin™ (¹⁷⁷Lu-Dota-tetulomab) is a pharmaceutical product candidate consisting of a radionuclide conjugated to a tumor seeking carrier/antibody, which can be used for irradiation of malignant metastasized tumors with minimal damage to nearby healthy normal tissue.

Disease: relapsed CD37 positive non-Hodgkin lymphoma

Therapeutic area: Cancer - Oncology

Country: Norway, Sweden

Trial details: The LYMRIT 37-01 study is an ongoing Phase 1/2 open label, single injection ascending dose study investigating in three dose levels of Betalutin® and different pre-dosing regimens in patients with relapsed NHL with the aim of identifying an optimal dose regimen to take into a pivotal Phase 2 PARADIGME trial. The Phase I part of the study is a dose escalating study to define the maximum tolerable dose of 177Lu-DOTA-HH1 (Betalutin), assess safety and toxicity, pharmacokinetics, biodistribution and efficacy. After completion of the phase I study, a dose will be selected for the phase II part of the study which is designed to investigate tumour response rate, progression free survival, confirmation of the selected dose as well as safety and toxicity. (NCT01796171)    

Latest news:

• • On May 19, 2017, Nordic Nanovector announced that the Safety Review Committee (SRC) for the ongoing LYMRIT 37-01 clinical trial of Betalutin® in non-Hodgkin’s Lymphoma (NHL) has reviewed safety data from the study and approved continued clinical evaluation of 20 MBq/kg Betalutin® administered after pre-dosing with 100 mg/m2 lilotomab. Following the SRC’s recommendation, new patients will be enrolled into a Phase 2 expansion cohort of Arm 4 in Betalutin’s Phase 1/2 study LYMRIT 37-01, to continue the collection of safety and efficacy data of 20 MBq/kg Betalutin® after pre-dosing with 100 mg/m2 lilotomab. This will enable the company to build a robust database of clinical data to confirm the optimal dosing regimen for the pivotal Phase 2 PARADIGME study, which is on track to start in the second half of 2017. Updated results from LYMRIT 37-01 have been accepted for presentation at the International Conference on Malignant Lymphoma (ICML), June 14-17 in Lugano, Switzerland. • On April 28, 2017, Nordic Nanovector announced that an abstract reporting updated results from the ongoing LYMRIT 37-01 Phase 1/2 clinical study of Betalutin® (177Lu-satetraxetan-lilotomab) in patients with relapsed/refractory non-Hodgkin’s lymphoma (NHL) has been accepted for presentation at the International Conference on Malignant Lymphoma (14-ICML, June 14-17, Lugano, Switzerland). The poster will be presented by Dr. Arne Kolstad, Senior Consultant in Medical Oncology and Radiation Therapy at the Oslo University Hospital, Norwegian Radium Hospital, and the study’s Principal Investigator.
• • On November 4, 2016, Nordic Nanovector announced that the independent Safety Review Committee (SRC) for the ongoing Lymrit 37-01 clinical trial of Betalutin® in relapsed/refractory NHL, has recommended escalating the dose of Betalutin® in Arm 4 from 15 MBq/kg to 20 MBq/kg following pre-dosing with 100 mg/m2 lilotomab. Recruitment of 3 patients into Arm 4 to receive this new higher dosing regimen is now underway. The SRC also concluded that Arm 3 should be discontinued. The decision follows a review by the SRC of the available safety and dosimetry data from the first cohorts of 3 patients each enrolled in Arms 3 and 4 to determine which arm should continue, if dose escalation is warranted and to what extent. Patients in Arm 3 were pre-dosed with standard rituximab immunotherapy prior to receiving 15 MBq/kg Betalutin®; patients in Arm 4 received 100 mg/m2 lilotomab prior to 15 MBq/kg Betalutin®.
• The SRC recommendation for advancing Arm 4 was based on safety data demonstrating that pre-dosing with 100 mg/m2 lilotomab prior to Betalutin® reduces bone marrow toxicity as a result of lower absorbed radiation dose to this tissue. In addition, available dosimetry data from Arm 4 showed that higher pre-dosing does not prevent therapeutically relevant amounts of Betalutin® being taken up into the tumours.
• The SRC has also agreed that the company can change the treatment regimen used in Arm 1/Phase 2 to match that used in Arm 4. The dose of Betalutin® specified in Phase 2 will be increased from 15 MBq/kg to 20 MBq/kg pending review of the safety data from the first 3 patients treated in Arm 4 with 20 MBq/kg.
• Escalation to the new higher dosing regimen in Arm 1/Phase 2 will also require the approval of a protocol amendment by the European regulators. The planned amendment will allow for additional patients to be enrolled into Arm 1/Phase 2, which is expected to contribute to building a more robust safety database, particularly with data from patients receiving the new higher dosing regimen. Updated results from this trial including those in Arms 3 and 4, will be presented at the 58th Annual American Society of Hematology (ASH) meeting on 3 December 2016.
• • On August 18, 2016, Nordic Nanovector announced that the first cohorts of both Arm 3 and 4 of the expanded Lymrit 37-01 clinical study with Betalutin® have been completed. Arm 3 is investigating the safety and efficacy of Betalutin® in relapsed FL patients pre-dosed with standard anti-CD20 immunotherapy (rituximab) on Day 0, a few hours prior to the administration of 15 MBq/kg Betalutin®.  Arm 4 is investigating the safety and efficacy of Betalutin® in relapsed FL patients pre-dosed with high-dose unconjugated “cold” lilotomab (previously referred to as HH1) anti-CD37 antibody on Day 0, a few hours prior to the administration of 15 MBq/kg Betalutin®.
• • On May 18, 2016, Nordic Nanovector announced that the first patient has been enrolled into the second of the two new arms, and the last cohort, of its expanded Lymrit 37-01 clinical study with Betalutin®. The final cohort (Arm 4) is designed to investigate the safety and efficacy of Betalutin® in up to 12 patients with relapsed FL pre-dosed with high-dose unconjugated “cold” HH1 anti-CD37 antibody on Day 0, a few hours prior to the injection of Betalutin®.
• • On October 15, 2015, Nordic Nanovector announces that it has taken the decision to revise its clinical development plan for Betalutin®, its lead product candidate in development for the treatment of major types of non-Hodgkin’s lymphoma (NHL), including Follicular Lymphoma. The revised clinical development plan sees the previous dose-finding element of the pivotal PARADIGME trial being expanded and integrated into the Phase 1/2 (Lymrit 37-01) trial that is currently underway. Previously, the dose-finding element was to be conducted in parallel as a ‘run-in’ phase to PARADIGME to potentially accelerate the time to approval. PARADIGME is now being planned as a single arm efficacy and safety trial. The revised Phase 1/2 trial is projected to read out around the end of Q1 2017 and will allow the selection of the optimal dosing regimen to be used for the amended PARADIGME trial, which is now expected to start in 1H 2017. As a result, the first regulatory submission for Betalutin® is expected in the 1H 2019. Based on the current plan, the Company expects that cash resources will be sufficient to reach the first regulatory submission despite the extended timelines. This is due to the overall reduction in patient numbers required for the PARADIGME study in the revised plan.
• • On June 17, 2015, Nordic Nanovector announced updated results of its ongoing Phase 1/2 study with Betalutin™ in relapsed CD37+ non-Hodgkin lymphoma (NHL) patients. Data and analysis are presented in a poster (abstract 287) at the 13th International Conference on Malignant Lymphoma (13-ICML, Lugano, Switzerland) by Dr. Arne Kolstad, Senior Consultant in Medical Oncology and Radiation Therapy at the Oslo University Hospital, Norwegian Radium Hospital, and the study’s Principal Investigator. This Phase 1/2 single dose, open label, dose-finding study is investigating three dose levels of Betalutin™ in 13 patients with relapsed CD37+ NHL, previously treated with a number of regimens ranging from 1 to 8. The updated data confirm the favourable safety profile of Betalutin™ and its promising efficacy. New data also highlight that clinical responses observed are sustained, with 5 out of 7 patients still in response, and a duration of response ranging from 6 to 21+ months. Other key findings are consistent with those presented at the American Society of Hematology (ASH) Conference in December 2014, and include:
• • Betalutin™ is well tolerated, with a predictable and manageable safety profile: most adverse events are haematological in nature, all transient and reversible;
• • 15 MBq/kg b.w. Betalutin™ with HH1 pre-dosing is currently recommended for part 2 of this Phase 1/2 study. This dose was endorsed by the Safety Review Committee;
• • Betalutin™ delivers a highly favourable response rate (best response) in this patient population (Overall Response Rate 64% and Complete Response 36%).
• Further updates will be presented at future conferences. A new study arm is currently open for enrolment to evaluate safety and efficacy of both 15 MBq/kg b.w. and 17.5 MBq/kg b.w. without HH1 pre-dosing. Cristina Oliva, Nordic Nanovector’s Chief Medical Officer, commented: “Based on these encouraging data, we are eager to continue the clinical development of Betalutin as a promising therapeutic option for the treatment of patients with relapsed non-Hodgkin lymphoma. We will continue the assessment of the safety and efficacy of Betalutin in this ongoing Phase 1/2 study and we are moving ahead with our pivotal Phase 2 study, PARADIGME, in relapsed/refractory CD37+ follicular lymphoma patients, which is expected to commence in the coming months.”
• • On March 27, 2014, Nordic Nanovector has announced that its lead product candidate Betalutin™ has achieved the two major objectives from the phase I portion of the ongoing phase I/II clinical trial. The ongoing trial has demonstrated that Betalutin™ is safe and well tolerated in patients suffering from non-Hodgkin lymphoma and that the product has a clinically relevant effect in this patient population.
• The positive results from Phase I has enabled the company to establish the dose interval for the Phase II part of the clinical trial , which will assess the efficacy of Betalutin™ in patients suffering from relapsed Non-Hodgkin Lymphoma.

Is general: Yes