Conditions: Advanced Solid Tumors
Keywords: Avelumab M9241 NHS-IL12 Advanced Solid Tumors
Allocation: NON_RANDOMIZED | Intervention model: SEQUENTIAL
Enrollment: 52
Healthy volunteers: no

Brief summary:
The study consisted of 2 parts: Dose Escalation phase (Part A) and Expansion phase (Part B). The dose escalation phase evaluated the safety, tolerability, and PK of avelumab in combination with M9241 in subjects with locally advanced, unresectable, or metastatic solid tumors. Expansion phase assessed the safety and clinical activity of the combination regimen in selected tumor types. In Expansion phase subjects who had completed the combination treatment of avelumab at a given dose level of M9241, a safety review was performed by the Safety monitoring committee in order to make a decision on the next dose level. Successive cohorts of 3 to 6 subjects were treated with escalating doses of M9241 with avelumab intravenous (IV).

Detailed description:

Arms:
arm 1: Participants received M9241 at a dose of 4 micrograms per kilogram (mcg/kg) a subcutaneous (SC) injection at time (up to -20 minutes) relative to the start of Avelumab infusion (time 0), once every 4 weeks, on Day 1 in combination with Avelumab 10 milligrams per kilogram (mg/kg) intravenous (IV) infusion every 2 weeks on Day 1 and 15 during each cycle (Each cycle=28 days) until any criterion for treatment discontinuation were met. arm 2: Participants received M9241 at a dose of 8 mcg/kg SC injection at time (up to -20 minutes) relative to the start of avelumab infusion (time 0), once every 4 weeks, on Day 1 in combination with Avelumab 10 mg/kg IV infusion every 2 weeks on Day 1 and 15 of each cycle (Each cycle=28 days) until any criterion for treatment discontinuation were met. arm 3: Participants received M9241 at a dose of 12 mcg/kg SC injection at time (up to -20 minutes) relative to the start of avelumab infusion (time 0), once every 4 weeks, on Day 1 in combination with Avelumab 10 mg/kg IV infusion every 2 weeks on Day 1 and 15 of each cycle (Each cycle=28 days) until any criterion for treatment discontinuation were met. arm 4: Participants received M9241 at a dose of 16.8 mcg/kg SC injection at time (up to -20 minutes) relative to the start of avelumab infusion (time 0), once every 4 weeks, on Day 1 in combination with Avelumab 10 mg/kg IV infusion every 2 weeks on Day 1 and 15 of each cycle (Each cycle=28 days) until any criterion for treatment discontinuation were met. arm 5: Participants received M9241 at a dose of 16.8 mcg/kg SC injection at time (up to -20 minutes) relative to the start of avelumab infusion (time 0), once every 4 weeks, on Day 1 in combination with Avelumab 800 milligrams (mg) IV infusion once weekly for the first 12 weeks, then 800 mg once every 2 weeks of each cycle (Each cycle=28 days) until any criterion for treatment discontinuation were met. arm 6: Participants in the expansion cohorts received M9241 at dose of 16.8 mcg/kg SC injection at time (up to -20 minutes) relative to the start of avelumab infusion (time 0), once every 4 weeks on Day 1 in combination with Avelumab 800 mg IV infusion once weekly for the first 12 weeks, then 800 mg once every 2 weeks of each cycle (Each cycle=28 days) determined as the RP2D in the escalation part of the study.

Interventions: intervention 1: Avelumab intervention 2: M9241 intervention 3: Avelumab (Once weekly) intervention 4: M9241 (MTD) intervention 5: Avelumab (Expansion cohort)
Intervention descriptions: intervention 1: Participants received avelumab intravenous (IV) infusion once a week on Day 1 and Day 15 of each cycle. intervention 2: Participants received Subcutaneous (SC) injection of M9241 in escalating doses on Day 1 of each cycle. intervention 3: Participants received avelumab once weekly in combination with M9241 every 4 weeks at M9241 maximum tolerated dose (MTD) for first 12 weeks followed by avelumab once every 2 weeks plus M9241 once every 4 weeks at M9241 MTD until a criterion for treatment discontinuation has been met. intervention 4: Participants received M9241 at M9241 MTD once every 4 weeks until a criterion for treatment discontinuation has been met. intervention 5: Participants in the expansion cohorts received Induction Therapy (Avelumab once weekly + M9241 once every 4 weeks) through Cycle 3 (for 12 weeks) then starting at Cycle 4, Continuation Therapy (Avelumab once every 2 weeks + M9241 once every 4 weeks).

Protocol document:
Prot_000.pdf: 























































































































































































































































































































































































SAP_001.pdf: 




































































































































































ELECTRONIC SIGNATURES
Document: ctp-ms201781-0031-sap-main-body-v2-0
Signed By
Event Name
Meaning of Signature
Server Date
(dd-MMM-yyyy
HH:mm ‘GMT’Z)
Task Completed (Approval
eSign): Approved
Business Approval
22-Oct-2020 07:37
Task Completed (Approval
eSign): Approved
Technical Approval
22-Oct-2020 14:16
Document No. 
Object No. 
PPD
PPD
CCI
CCI


































































































































































ELECTRONIC SIGNATURES
Document: ctp-ms201781-0031-sap-expansion-v2-0
Signed By
Event Name
Meaning of Signature
Server Date
(dd-MMM-yyyy
HH:mm ‘GMT’Z)
Task Completed (Approval
eSign): Approved
Business Approval
22-Oct-2020 07:45
Task Completed (Approval
eSign): Approved
Technical Approval
22-Oct-2020 14:15
Document No. 
Object No. 
CCI
CCI
PPD
PPD