Vimseltinib (1) – Romvimza®

• Clinical trials
  • To assess the extent of the additional benefit of vimseltinib in the therapeutic indication for tenosynovial giant cell tumours (TGCT), the pharmaceutical manufacturer submitted data from the multicentre, randomised, placebo-controlled, multi-part Phase III MOTION trial, which has been underway since October 2021 at 30 study centres in North America, Europe and Asia.
  • The ongoing MOTION trial compares vimseltinib (+ best supportive care, BSC) with placebo (+ BSC) in adults with symptomatic TGCT [...]

Adults with symptomatic tenosynovial giant cell tumours (Tenosynovial Giant Cell Tumours, TGCT), which are associated with a clinically relevant deterioration in physical functioning and for whom surgical options have been exhausted or would result in unacceptable morbidity or disability

• Indication of considerable additional benefit
• Overall, the G-BA concludes that there is an indication of the established additional benefit based on the strength of the evidence.
• Consequently, a considerable additional benefit of vimseltinib + BSC compared with placebo + BSC can be concluded overall in adults with symptomatic tenosynovial giant cell tumours (Tenosynovial Giant Cell Tumours, TGCT) associated with a clinically relevant deterioration in physical functioning, and in whom surgical options have been exhausted or would lead to unacceptable morbidity or disability.
• mortality
  • In the Motion study, deaths were recorded as AEs leading to death as part of the safety monitoring. No deaths occurred.
• morbidity
  • In the MOTION study, tumour response or the ‘objective response rate’ (ORR) is defined as the proportion of study participants with a complete response (CR) or partial response (PR) at week 25, where CR and PR are defined as follows:
  • CR: Disappearance of all target lesions. All pathological lymph nodes must be less than 10 mm in the short axis. Non-nodular target lesions must have disappeared.
  • PR: At least a 30% reduction in the sum of the diameters of the target lesions, with the sum of the baseline diameters serving as the reference.
  • Tumour response was assessed by independent radiological review (IRR) in accordance with the Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1 criteria and was therefore not symptom-based but determined primarily on the basis of imaging procedures. For this reason, this endpoint is classified as not patient-relevant.
  • Physical function was assessed in the MOTION study using 15 questions from the standardised item bank of the ‘Patient-Reported Outcomes Measurement Information System Physical Function’ (PROMIS PF), as well as via the self-reported PGIC-PF and PGIS-PF questionnaires.
  • The results show a statistically significant and clinically relevant difference in favour of vimseltinib for the physical function endpoint as measured by PROMIS PF at week 25. A statistically significant improvement was also observed for vimseltinib in both the PGIC-PF and PGIS-PF.
  • With regard to the available results for the PGIC/PGIS-PF, there is a potential for double-counting concerning the ‘physical function’ endpoint. Overall, the results for the PGIC/PGIS-PF are therefore interpreted as confirming the results of the PROMIS PF.
  • For the endpoint ‘stiffness’ as measured by the NRS, a statistically significant advantage of vimseltinib was observed at week 25. A statistically significant improvement was also observed for vimseltinib on the PGIC-ROM.
  • With regard to the available results for the PGIC-ROM, there is also a potential for double counting with respect to the endpoint ‘restrictions in range of motion’. Overall, the results for the PGIC-ROM are therefore interpreted as confirming the results for NRS stiffness.
  • At week 25, a statistically significant advantage in favour of vimseltinib compared with baseline was observed.
  • Active range of motion is not considered to be of direct relevance to patients and is presented only as supplementary information.
  • For both the ‘pain’ and ‘average pain’ scales, a statistically significant and clinically relevant advantage of vimseltinib is observed at week 25.
  • For the health status endpoint, as measured by the EQ-5D VAS, a statistically significant advantage in favour of vimseltinib was observed at week 25.
  • For the PGIC disease symptoms measure, a statistically significant improvement was observed for vimseltinib.
  • In the overall analysis of the morbidity endpoint category, consistent and clear advantages for vimseltinib were observed across almost all endpoints.
• quality of life
  • No data on health-related quality of life were collected in the MOTION study.
• Side effects
  • In the MOTION study, adverse events (AEs) occurred in almost all patients in both treatment arms. The results are presented here for supplementary information only.
  • For the endpoints of SAEs and therapy discontinuations due to AEs, there was no statistically significant difference between the treatment arms in either case.
  • For the endpoint of severe AEs, there was a statistically significant disadvantage of vimseltinib + BSC compared with placebo + BSC.
  • In summary, the side effects associated with vimseltinib show disadvantages due to the increase in severe adverse events.
• Overall assessment
  • No deaths occurred in the MOTION trial.
  • For the morbidity endpoint category, treatment with vimseltinib showed the following results when considering the endpoints ‘Physical Functioning’ (as measured by PROMIS PF and PGIC/PGIS-PF), ‘worst pain’ and ‘average pain’ (both measured using the BPI-SF), ‘Restrictions in range of motion’ (using NRS stiffness and PGIC-ROM), ‘Health status’ using EQ-5D VAS, and the PGIC disease symptoms, vimseltinib showed a clear overall advantage.
  • No data were collected on the endpoint category of health-related quality of life in the MOTION study.
  • In the endpoint category of side effects, vimseltinib showed a disadvantage due to a significant increase in severe AEs; no differences were observed in the endpoints of serious AEs or therapy discontinuations due to AEs.
  • Overall, the consistently positive effects on morbidity (physical functioning, pain, limitations in range of motion and health status) are offset by a negative effect in the ‘side effects’ endpoint category (severe AEs). The negative effect is assessed as not calling into question the extent of the additional benefit resulting from the marked improvement in morbidity.
• Overall view
  • Overall, there are consistently positive effects across almost all endpoints in the morbidity category. In contrast, there is a disadvantage in terms of side effects due to the increase in severe AEs, which, however, does not call into question the consistent advantages in terms of morbidity.
  • Overall, a considerable additional benefit of vimseltinib is observed.

Courtesy translation only, please refer to the German original.