A Randomised, Open-Label, Phase 2 Study of Ceralasertib Monotherapy and Ceralasertib plus Durvalumab in Patients with Unresectable or Advanced Melanoma and Primary or Secondary Resistance to PD-(L)1 Inhibition

Conditions

Unresectable or Advanced Melanoma

Brief summary

The primary measure is the estimate of ORR for each experimental treatment arm, and a secondary measure of interest is the odds ratio of the ORR comparing the 2 treatment arms., Biopsy Sub-study: CD8+ T cells tumour infiltration assessed in baseline, on-treatment and off-treatment tumour biopsies.

Detailed description

Median and landmark DoR estimates at 6, 9, 12, 15, and 18 months, Median TTR and proportion of patients with response at the first scheduled tumour assessment, Percentage change from baseline in TL tumour size at week 16 and best percentage change from baseline, Median and landmark PFS at 3, 6, 9, 12 months, and the hazard ratio comparing the 2 treatment arms, Median and landmark OS at 6, 9, 12, and 18 months, and the hazard ratio comparing the 2 treatment arms, Concentration of ceralasertib in plasma (peak and trough concentrations, as data allow; sparse sampling), Biopsy Sub-study: As described for the main study, using the investigator assessment of tumour response per RECIST 1.1, Biopsy Sub-study: Pre-treatment presence and/or on-treatment and/or off-treatment changes in PD-L1 and pRAD50, Biopsy Sub-study: Proliferation (using Ki67+ marker) of carcinoma and/or immune cells (including CD8+ T cells) will be assessed in baseline, on-treatment and off-treatment tumour biopsies

Related papers

No related papers found yet.

Interventions

DRUGMycophenolate Mofetil 250 mg Capsules

DRUGInflectra 100 mg powder for concentrate for solution for infusion

DRUGCeralasertib

DRUGIMFINZI 50 mg/mL concentrate for solution for infusion.

Eligibility

Sex/Gender

All

Age

18 Years to No maximum

Design outcomes

Primary

Measure	Time frame
The primary measure is the estimate of ORR for each experimental treatment arm, and a secondary measure of interest is the odds ratio of the ORR comparing the 2 treatment arms., Biopsy Sub-study: CD8+ T cells tumour infiltration assessed in baseline, on-treatment and off-treatment tumour biopsies.	—

Secondary

Measure	Time frame
Median and landmark DoR estimates at 6, 9, 12, 15, and 18 months, Median TTR and proportion of patients with response at the first scheduled tumour assessment, Percentage change from baseline in TL tumour size at week 16 and best percentage change from baseline, Median and landmark PFS at 3, 6, 9, 12 months, and the hazard ratio comparing the 2 treatment arms, Median and landmark OS at 6, 9, 12, and 18 months, and the hazard ratio comparing the 2 treatment arms, Concentration of ceralasertib in plasma (peak and trough concentrations, as data allow; sparse sampling), Biopsy Sub-study: As described for the main study, using the investigator assessment of tumour response per RECIST 1.1, Biopsy Sub-study: Pre-treatment presence and/or on-treatment and/or off-treatment changes in PD-L1 and pRAD50, Biopsy Sub-study: Proliferation (using Ki67+ marker) of carcinoma and/or immune cells (including CD8+ T cells) will be assessed in baseline, on-treatment and off-treatment tumour biopsies	—

Measure

Time frame

Median and landmark DoR estimates at 6, 9, 12, 15, and 18 months, Median TTR and proportion of patients with response at the first scheduled tumour assessment, Percentage change from baseline in TL tumour size at week 16 and best percentage change from baseline, Median and landmark PFS at 3, 6, 9, 12 months, and the hazard ratio comparing the 2 treatment arms, Median and landmark OS at 6, 9, 12, and 18 months, and the hazard ratio comparing the 2 treatment arms, Concentration of ceralasertib in plasma (peak and trough concentrations, as data allow; sparse sampling), Biopsy Sub-study: As described for the main study, using the investigator assessment of tumour response per RECIST 1.1, Biopsy Sub-study: Pre-treatment presence and/or on-treatment and/or off-treatment changes in PD-L1 and pRAD50, Biopsy Sub-study: Proliferation (using Ki67+ marker) of carcinoma and/or immune cells (including CD8+ T cells) will be assessed in baseline, on-treatment and off-treatment tumour biopsies

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Countries

Belgium, France, Germany, Italy, Poland, Spain

Outcome results

None listed