Patients should be study treatment after an by the RMP evaluator to treated with Keytruda initial disease more clearly define until disease assessment of disease progression, and progression or progression until a to consider the unacceptable toxicity. second disease acceptability of the Atypical responses (that assessment at least 4 underlined statement in is, an initial transient weeks later was the proposed form. increase in tumour size performed. If disease It is recommended to the or small new lesions progression is Delegate that additional within the first few confirmed, then patients wording, as it is included months followed by should discontinue in the US prescribing tumour shrinkage) have Keytruda; if disease information, be included been observed. Clinical progression is not in the Australian PI. This stable patients with confirmed, then patients will provide a clearer initial evidence of may continue Keytruda. description as to how disease progression In the U.S. prescribing disease progression was should remain on information, the above determined during the treatment until disease language was included clinical development progression is in the initial labelling program, and will confirmed. The RMP information proposed to provide guidance to evaluator raises the FDA. After FDA review, physicians as to how following issues: A.) It language on patient disease progression may be appropriate for management in P001 should be defined in the the sponsor to provide was relocated to the context of treatment further clarification clinical studies section, with pembrolizumab. about how disease and reworded as progression should be follows: defined, in order to were justify cessation of ‘Patients randomised to receive 2 treatment with mg/kg (n = 89) or Keytruda, B.) The 10 mg/kg (n = 84) of underlined writing is not Keytruda Q3W until included in the US unacceptable toxicity or monograph, where the disease progression that product is registered was symptomatic, was since September 2014. rapidly progressive, required urgent intervention, occurred with a decline in performance status, or was confirmed at 4 to 6 weeks with repeat imaging.’ Amendments to the PI The amended PI is A.) The sponsor has and CMI as follows: In provided. added a statement as regard to the proposed recommended. routine risk Pending the Delegate’s minimisation activities, approval, this is it is recommended to the considered acceptable. Delegate that the PI B.) The sponsor has not be revised as follows: included a statement as
Patients should be treated with Keytruda until disease progression or unacceptable toxicity. Atypical responses (that is, an initial transient increase in tumour size or small new lesions within the first few months followed by tumour shrinkage) have been observed. Clinical stable patients with initial evidence of disease progression should remain on treatment until disease progression is confirmed. The RMP evaluator raises the following issues: A.) It may be appropriate for the sponsor to provide further clarification about how disease progression should be defined, in order to justify cessation of treatment with Keytruda, B.) The underlined writing is not included in the US monograph, where the product is registered since September 2014. study treatment after an initial disease assessment of progression until a second disease assessment at least 4 weeks later was performed. If disease progression is confirmed, then patients should discontinue Keytruda; if disease progression is not confirmed, then patients may continue Keytruda. In the U.S. prescribing information, the above language was included in the initial labelling information proposed to FDA. After FDA review, language on patient management in P001 was relocated to the clinical studies section, and reworded as follows: ‘Patients were randomised to receive 2 mg/kg (n = 89) or 10 mg/kg (n = 84) of Keytruda Q3W until unacceptable toxicity or disease progression that was symptomatic, was rapidly progressive, required urgent intervention, occurred with a decline in performance status, or was confirmed at 4 to 6 weeks with repeat imaging.’ by the RMP evaluator to more clearly define disease progression, and to consider the acceptability of the underlined statement in the proposed form. It is recommended to the Delegate that additional wording, as it is included in the US prescribing information, be included in the Australian PI. This will provide a clearer description as to how disease progression was determined during the clinical development program, and will provide guidance to physicians as to how disease progression should be defined in the context of treatment with pembrolizumab. Amendments to the PI and CMI as follows: In regard to the proposed routine risk minimisation activities, it is recommended to the Delegate that the PI be revised as follows: The amended PI is provided. A.) The sponsor has added a statement as recommended. Pending the Delegate’s approval, this is considered acceptable. B.) The sponsor has not included a statement as