Glofitamab (1) – Columvi®

• Clinical trials
  • The NP30179 trial is a single-arm, ongoing Phase I/II dose-escalation and dose-expansion trial in people with relapsed or refractory (R/R) B-cell non-Hodgkin’s lymphoma.

Adults with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) following two or more lines of systemic treatment

• In summary, the additional benefit of glofitamab is assessed as follows: a hint of a non-quantifiable additional benefit, as the scientific evidence does not permit quantification.
• Overall, the extent of the additional benefit is classified as non-quantifiable, as the scientific evidence does not permit quantification.
• Overall, with regard to the strength of the evidence, there is a hint of a non-quantifiable additional benefit.
• mortality
  • For the benefit assessment, the analysis of overall survival for the ITT population of the pooled cohorts D2 [Sub.2] and D3 of study NP30179 was used for the benefit assessment, as many individuals in cohort D5 had already been censored before month 12.
  • Of the 115 participants in the ITT population, 65 (56.5%) had died by the analysis date of 15 June 2022.
  • It is not possible to interpret or evaluate the mortality data due to the lack of a control group. Consequently, no conclusions regarding the extent of the additional benefit can be drawn for the mortality category.
• Morbidity – Progression-free survival (PFS)
  • In the NP30179 study, PFS was assessed as a secondary endpoint. PFS was defined as the time from the first dose of the study medication to disease progression (PD) or death from any cause, whichever occurred first. PFS was assessed by an independent review committee (IRC) in accordance with the 2014 Lugano criteria.
  • The PFS endpoint is a composite endpoint comprising endpoints from the categories of mortality and morbidity. In this study, the ‘mortality’ component of the endpoint was recorded as a separate endpoint via the ‘overall survival’ endpoint. In accordance with the operationalisation, the morbidity component was assessed not on the basis of symptoms, but exclusively by means of imaging procedures.
  • Taking the above aspects into account, there are differing views within the G-BA regarding the clinical relevance of the PFS endpoint. The overall conclusion regarding the extent of the additional benefit remains unaffected by this, as there is no control group and no conclusion regarding the extent of the additional benefit can be drawn. The PFS endpoint is presented for supplementary information.
  • Notwithstanding this, no conclusion regarding the extent of the additional benefit can be drawn from the results of the NP30179 study on the tumour response endpoint, as there is no control group.
• Health-related quality of life
  • Data on quality of life were collected in the NP30179 study using the EORTC QLQ-C30. The same criticisms apply as those described under the ‘Morbidity’ category, in the ‘Symptoms’ section, regarding the EORTC QLQ-C30.
  • Due to the aforementioned inconsistencies between the study documents and the dossier documents, as well as the discrepancies addressed regarding the different reference population, the response rates incorrectly calculated by the pU, and the submitted responder analysis, we have decided not to present the quality of life results using the EORTC QLQ-C30.
  • Nevertheless, no conclusions regarding the extent of the additional benefit can be drawn from the results of the NP30179 study on quality of life, as there is no control group.
• Side effects
  • The analyses regarding side effects relate to adverse events (AEs) that occurred in the safety population (N = 154) from the time of administration of the study medication up to 90 days after the last dose.
  • Total adverse events (AEs)
  • An adverse event occurred in almost all adults in the ITT population (152 out of 154 patients (98.7 %)). These are presented here for information only.
  • Serious adverse events (SAEs)
  • At least one serious adverse event occurred in 75 of the 154 patients (48.7 %).
  • Severe adverse events (CTCAE grade ≥ 3)
  • At least one severe AE with a CTCAE grade of ≥ 3 occurred in 99 out of 154 patients in the ITT population (64.3%).
  • Therapy discontinuation due to adverse events
  • In 14 patients (9.1%), an adverse event occurred that led to discontinuation of the study medication.
  • Specific AEs
  • Serious adverse events with an incidence of ≥ 5 % of patients by system organ class (SOC) included disorders of the immune system (22.1 %), infections and parasitic diseases (18.2 %), blood and lymphatic system disorders (6.5 per cent) and benign, malignant and unspecified neoplasms (including cysts and polyps) (5.2 per cent).
  • Severe adverse events of CTCAE grade ≥ 3 with an incidence of ≥ 5% of patients, by system organ class (SOC), were disorders of the blood and lymphatic system (35.1%), infections and parasitic diseases (16.9 per cent), investigations (11.7 per cent) and metabolic and nutritional disorders (11.0 per cent).
  • In summary, no conclusions can be drawn regarding the extent of the additional benefit for the ‘side effects’ category, as there is no control group.
• Overall assessment / Conclusion
  • The data available for the benefit assessment come from the single-arm study NP30179, which formed the basis for marketing authorisation. No further data are available, nor is there any indirect comparison.
  • As no comparative data are available, no conclusion can be drawn regarding the extent of the additional benefit on the basis of these results.
  • In summary, the available results are classified as non-quantifiable in their overall assessment, as the scientific evidence does not permit quantification.
• Overall assessment / Conclusion
  • The data available for the benefit assessment are from the single-arm study NP30179, on which the marketing authorisation is based. No further data are available, nor is there any indirect comparison.
  • As no comparative data are available, no conclusion can be drawn regarding the extent of the additional benefit on the basis of these results.
  • In summary, the available results are, when viewed as a whole, classified as non-quantifiable in terms of their extent, as the scientific data do not permit quantification.

Courtesy translation only, please refer to the German original.