This Study is a Phase II Study of AZD6738 in Combination With Durvalumab in Patients With Solid Tumor (Cohort A (N=30): GC Who Have Failed Secondary Chemotherapy Treatments Regimen; Cohort B (B=30): Melanoma Patients Who Have Failed to IO)

Malignant Melanoma Clinical Trial

Official title: Phase II Study of AZD6738 in Combination With Durvalumab (MEDI4736), in Patients With Metastatic Solid Tumor as Salvage Treatment

Status Active, not recruiting

Clinical Trial Summary

This study is a phase II study of AZD6738 in combination with durvalumab in patients with solid tumor (cohort A (N=30): GC who have failed secondary chemotherapy treatments regimen; cohort B (B=30): melanoma patients who have failed to IO). Patients will receive AZD6738 plus durvalumab combination regimen.

AZD6738 will be administered at 240 mg twice daily on days 1 to 7 in Cycle 0 (lead-in period) and therafter at 240 mg BD on days 22 to 28 in a 28-day cycle. Durvalumab will be administered at 1500 mg every 4 weeks from cycle 1 day 1.

Tumour evaluation using modified RECIST 1.1 will be conducted at screening (within 28 days prior to first dose) and every 8 weeks relative to the date of first dose, up to week 40, then every 12 weeks until objective disease progression (within a window of +/- 7 days of the scheduled date).

Patients will continue to receive treatment with AZD6738 and durvalumab provided that the treatment is tolerable and there is evidence of clinical benefit (as judged by the investigator) and secure supply of medication. Upon confirmation of objective disease progression, or treatment disconiutation criteria are met, both durvalumab and AZD6738 must be discontinued. Patients may continue with AZD6738/durvalumab beyond objective disease progression (determined by modified RECIST 1.1) at the discretion of the investigator if they are clinically benefiting from the treatment and they do not meet any other discontinuation criteria.

If either durvalumab and/or AZD6738 are deemed intolerable (as judged by the investigator) so that discontinuation of either agent is deemed in the patient's best interest despite dose interruptions, dose modification and initiation of supportive treatments, both durvalumab and AZD6738 must be discontinued and the patient withdrawn from the study. Patients are not permitted to continue either AZD6738 or durvalumab as monotherapy. There is no maximum duration of treatment with AZD6738 and durvalumab.

The imaging modalities used for modified RECIST 1.1 assessment will be CT or MRI scans of chest,abdomen and pelvis. modified RECIST 1.1 scans will be analysed by the investigator on site.

Patients will also be requested to provide tumour samples from the primary or metastatic tumours pre-study and on progression. Sample provision is mandatory, subject to aspecific consent, and will aid understanding of resistance mechanisms. However, if biopsy site is not feasible, the protocol will allow waiving the rebiopsy procedure.

Clinical Trial Description

Target subject population

There will be two cohorts for this study:

Cohort A: Patients with refractory gastric cancer who have failed secondary chemotherapy treatments for advanced disease will be enrolled. Patients must have imaging confirmed progression on previous chemotherapy for gastric cancer treatment with at least one measurable lesion per modified RECIST 1.1. GC patients must not have received previous therapy with immune checkpoint inhibitors. Prior exposure to AZD6738 is not allowed.

Cohort B: Patients with metastatic melanoma patients who have failed prior anti-PD(L)1 will be enrolled. Anti-PD(L)1 therapy should be the immediate prior regimen before study entry.

Duration of treatment Patients will continue to receive treatment with AZD6738 and durvalumab provided that the treatment is tolerable and there is evidence of clinical benefit (as judged by the investigator) and secure supply of medication. Upon confirmation of objective disease progression, or treatment disconiutation criteria are met, both durvalumab and AZD6738 must be discontinued. Patients may continue with AZD6738/durvalumab beyond objective disease progression (determined by RECIST 1.1) at the discretion of the investigator if they are clinically benefiting from the treatment and they do not meet any other discontinuation criteria.

If either durvalumab and/or AZD6738 are deemed intolerable (as judged by the investigator) so that discontinuation of either agent is deemed in the patient's best interest despite dose interruptions, dose modification and initiation of supportive treatments, both durvalumab and AZD6738 must be discontinued and the patient withdrawn from the study. Pateints are not permitted to continue either AZD6738 or durvalumab as monotherapy. There is no maximum duration of treatment with AZD6738 and durvalumab. ;

Related Conditions & MeSH terms

• Gastric Adenocarcinoma
• Malignant Melanoma
• Melanoma

• NCT number: NCT03780608
• Study type: Interventional
• Source: Samsung Medical Center
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: July 30, 2019
• Completion date: December 1, 2023