Mosunetuzumab (1) – Lunsumio®

• Clinical trials
  • The GO29781 trial investigated the safety, pharmacokinetics and biological and clinical activity of mosunetuzumab as monotherapy or in combination with atezolizumab in adults with relapsed or refractory haematological malignancies.
  • The sub-cohort of the GO29781 study relevant to the benefit assessment comprises adults with relapsed or refractory follicular lymphoma (FL) following at least two prior systemic treatments, who were treated with the authorised dose of mosunetuzumab monotherapy.

Adults with relapsed or refractory follicular lymphoma (FL) who have already received at least two prior systemic treatments

• Hint for a non-quantifiable additional benefit, as the scientific data do not permit quantification.
• As only single-arm data are available and a comparative assessment is not possible, the certainty of the evidence is rated as a hint.
• mortality
  • Overall survival is defined in the GO29781 study as the time from the first dose of mosunetuzumab until death from any cause.
  • As of the data cut-off date of 27 August 2021, a total of 8 people (8.9%) had died. The median overall survival had not yet been reached.
  • Due to the single-arm study design, a comparative assessment of the overall survival results is not possible.
• Morbidity – Complete remission (CR; presented for supplementary information)
  • The primary endpoint of the GO29781 study is complete remission (CR), which was assessed by an independent review committee (IRF).
  • Assessment was carried out in accordance with the criteria set out by Cheson et al. (2007), primarily using imaging procedures. In addition, patients were required to show a complete resolution of symptoms.
  • It is unclear how many of the patients included in the sub-cohort relevant for evaluation were symptomatic at the start of the study, or how symptoms were recorded and documented. There is no separate breakdown of the CR results by symptomatic and asymptomatic patients. The results regarding CR are therefore presented only as supplementary information.
  • As of the data cut-off date of 27 August 2021, 60% of patients had achieved CR.
  • Due to the single-arm study design, a comparative assessment of the CR results is not possible.
• Morbidity – Health status (EQ-5D VAS)
  • Health status was assessed in the GO29781 study using the EuroQol 5-Dimensional Visual Analogue Scale (EQ-5D-VAS).
  • This analysis therefore presents the mean changes from baseline to cycle 4.
  • Due to the single-arm study design, a comparative assessment of the results for the EQ-5D VAS is not possible.
• Morbidity – EORTC QLQ-C30 (symptom scales)
  • Disease symptoms were assessed in the GO29781 study using the symptom scales of the EORTC-QLQ-C30 questionnaire.
  • Consequently, the data presented on the symptom scales of the EORTC QLQ-C30 are, on the whole, not usable for the present benefit assessment.
  • Notwithstanding this, a comparative assessment of the data on the EORTC QLQ-C30 is not possible due to the single-arm study design.
• Quality of life – EORTC QLQ-C30 (functional scales)
  • In the dossier, the pharmaceutical manufacturer presents, as at the data cut-off date of 27 August 2021, responder analyses with a cut-off value of 10 points, as well as analyses of the mean change from baseline for the physical functioning scale. This selective analysis of just one functional scale of the EORTC QLQ-C30 is not usable for the present benefit assessment.
  • Consequently, the data submitted on the functional scales of the EORTC QLQ-C30 are, on the whole, not usable for the present benefit assessment.
  • Notwithstanding this, a comparative assessment of the data on the EORTC QLQ-C30 is not possible due to the single-arm study design.
• Quality of life – FACT-LymS
  • Disease-specific quality of life was assessed using the validated Functional Assessment of Cancer Therapy – Lymphoma (FACT-Lym) questionnaire.
  • This assessment therefore presents the mean changes from baseline to cycle 6.
  • Due to the single-arm study design, a comparative assessment of the results for the FACT-LymS is not possible.
• Side effects
  • Adverse events occurred in all patients in the sub-cohort relevant to the analysis.
  • Severe adverse events (AEs) of CTCAE grade ≥ 3 occurred in 70%. An incidence of ≥ 5 % was observed in the System Organ Classes (SOCs) Blood and Lymphatic System Disorders, Metabolic and Nutritional Disorders, Infections and Parasitic Diseases, and Investigations.
  • Serious AEs occurred in 46.7%. An incidence of ≥ 5% was observed in the SOCs ‘Immune system disorders’, ‘Metabolism and nutrition disorders’ and ‘Infections and infestations’.
  • Four patients discontinued the study medication due to AEs.
  • AE of particular interest included, amongst others, cytokine release syndrome (CRS; graded according to Lee et al. (2014)), flare reactions, hepatic events, infections, and disorders of the nervous system and psychiatric disorders. The most common adverse events, occurring in approximately 69% of patients, were nervous system disorders and psychiatric disorders, followed by infections (approx. 51%) and CRS (approx. 46%). CRS was classified as serious in approximately 23% of patients.
  • Due to the single-arm study design, a comparative assessment of the results for the ‘side effects’ endpoint category is not possible.
• Overall assessment
  • The data available for this benefit assessment are from the single-arm Phase I/II trial GO29781. The patient population relevant to the assessment comprises patients with relapsed or refractory FL who have received at least two prior systemic therapies and were treated with a dose of mosunetuzumab monotherapy in accordance with the marketing authorisation. Data are available on mortality, morbidity, health-related quality of life and side effects.
  • Median overall survival had not yet been reached at the data cut-off date of 27 August 2021.
  • The analyses presented for the EORTC QLQ-C30 regarding the endpoint categories of morbidity and quality of life are not interpretable.
  • Severe adverse events (AEs) of CTCAE grade ≥ 3 occurred in 70% of patients, and serious AEs occurred in 46.7% of patients.
  • Due to the single-arm study design, a comparative assessment across all endpoint categories is not possible.
  • Overall, the extent of the additional benefit is classified as non-quantifiable, as the scientific evidence base does not permit quantification.

Courtesy translation only, please refer to the German original.