Retifanlimab (1) – Zynyz®

• Clinical trials
  • To assess the extent of the additional benefit of Retifanlimab in the therapeutic indication ‘first-line treatment of adult patients with metastatic or recurrent, locally advanced Merkel cell carcinoma (MCC) that is not suitable for curative surgery or radiotherapy”, the pharmaceutical manufacturer submitted the results of the pivotal, single-arm, open-label Phase II trial POD1UM-201.

Adult patients with metastatic or recurrent, locally advanced Merkel cell carcinoma (MCC) that is not suitable for curative surgery or radiotherapy; first-line

• Hint for a non-quantifiable additional benefit, as the scientific data do not permit quantification.
• For the benefit assessment of retifanlimab for the first-line treatment of adult patients with metastatic or recurrent, locally advanced Merkel cell carcinoma (MCC) that is not suitable for curative surgery or radiotherapy, the pharmaceutical manufacturer submitted the results of the pivotal, single-arm, open-label Phase II study POD1UM-201.
• Due to the single-arm design of the POD1UM-201 trial, no conclusion can be drawn regarding the extent of the additional benefit on the basis of the trial results.
• Consequently, the GBA classifies the extent of the additional benefit as non-quantifiable, as the scientific evidence does not permit quantification.
• mortality
  • In the POD1UM-201 trial, overall survival was defined as the time from the first dose of the study medication until death from any cause.
  • At the time of the final data cut-off, a total of 39 patients (38.6 per cent) had died.
  • Median overall survival had not been reached at the time of the data cut-off, with a median follow-up period of just under 3 years from enrolment (35.7 months).
  • The estimated probability of survival was 79.0% at one year, 67.0% at two years and 63.0% at three years.
  • Due to the single-arm study design, a comparative assessment of overall survival is not possible.
• Morbidity – Progression-free survival (PFS)
  • PFS was assessed as a secondary endpoint in the POD1UM-201 study.
  • It was defined as the period from the first dose of the study treatment to the first documented disease progression according to RECIST v1.1 or death from any cause, based on the assessment by an independent review committee (ICR).
  • The PFS endpoint in question is a composite endpoint comprising endpoints from the ‘mortality’ and ‘morbidity’ categories.
  • Nevertheless, due to the single-arm study design, a comparative evaluation is not possible.
• Morbidity – Objective Response Rate (ORR)
  • In the POD1UM-201 study, the ORR was defined as all patients with a confirmed overall response of ‘Complete Response’ or ‘partial response’ from baseline until disease progression or the start of a new cancer treatment, assessed in accordance with RECIST v1.1 by an independent review committee (ICR).
  • 55 of the patients (54.5 per cent) showed an objective response.
  • The ORR was assessed by means of independent radiological review and was therefore not symptom-based, but primarily based on imaging procedures.
  • For this reason, this endpoint is classified as not patient-relevant.
  • Notwithstanding this, no conclusions regarding the extent of the additional benefit can be drawn from the results of the POD1UM-201 study for the ORR endpoint, as a comparative assessment is not possible due to the single-arm study design.
• health status
  • Patients’ health status was assessed in the POD1UM-201 study using the VAS component of the EQ-5D questionnaire.
  • Due to minor response rates (< 70 % from the first post-baseline assessment), no suitable results on health status are available.
  • Regardless of this, a comparative assessment is not possible due to the single-arm study design.
• quality of life
  • Health-related quality of life was assessed in the POD1UM-201 study using the FACT-M.
  • Due to minor response rates (< 70% from the first post-baseline survey), no suitable results on quality of life are available.
  • Nevertheless, a comparative assessment is not possible due to the single-arm study design.
• Side effects – Total adverse events (AEs)
  • Almost all patients experienced an adverse event (91.1 per cent).
• Side effects – serious adverse events (SAEs)
  • At least one serious adverse event occurred in 26 out of 101 patients (25.7%).
• Side effects – Severe adverse events (CTCAE grade ≥ 3)
  • At least one severe AE with a CTCAE grade of ≥ 3 occurred in 32 out of 101 patients (31.7%).
• Side effects – Therapy discontinuation due to adverse events
  • In 21 out of 101 patients (20.8%), an adverse event occurred that led to discontinuation of the study medication.
  • Due to the single-arm study design, a comparative assessment of side effects is not possible.
• Overall assessment
  • Due to the single-arm design of the POD1UM-201 study, no conclusion can be drawn regarding the extent of the additional benefit based on the study results.
  • Overall, the GBA classifies the extent of the additional benefit of retifanlimab in metastatic or recurrent, locally advanced Merkel cell carcinoma (MCC) that is not suitable for curative surgery or radiotherapy is non-quantifiable, because the scientific evidence does not permit quantification.

Courtesy translation only, please refer to the German original.