ATr Inhibitor in Combination With Olaparib/Durvalumab (MEDI4736) in Gynaecological Cancers With ARId1A Loss or no Loss

Conditions

• Gynaecological Cancers

Eligibility Criteria

Sex

FEMALE

Age

18 Years - N/A

Healthy Volunteers

Not accepted

Interventions

• Ceralasertib — DRUG
  ATR inhibitor
• Olaparib — DRUG
  PARP inhibitor
• Durvalumab — DRUG
  Anti-PD-L1 immunotherapy

Study Details

ATARI trial tests the ATR inhibitor drug ceralasertib (AZD6738) alone and in combination with either a PARP inhibitor drug called olaparib, or an anti-PD-L1 immunotherapy called durvalumab (MEDI4736) in patients with relapsed gynaecological cancers to assess the response in groups of patients selected based on their cancer cell subtype and the presence of an abnormality in the ARID1A gene.

Key Dates

Start date

Nov 27, 2019

Status verified

Feb 2026

Primary completion

Aug 31, 2026

Completion

Aug 31, 2026

Study Design

Enrollment

174 participants (estimated)

Allocation

NON_RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Arms

• Experimental: 1A: ceralasertib (AZD6738)
  Women with relapsed ovarian (fallopian tube / primary peritoneal) and endometrial (uterus) clear cell carcinomas with loss of ARID1A expression treated with single agent AZD6738.
• Experimental: 1B: ceralasertib (AZD6738) + olaparib
  In second stage of trial, opening of this cohort depends on response rate in cohort 1A during first stage of trial. Women with relapsed ovarian (fallopian tube / primary peritoneal) and endometrial (uterus) clear cell carcinomas with loss of ARID1A expression treated with AZD6738 in combination with olaparib.
• Experimental: 2: ceralasertib (AZD6738) + olaparib
  Women with relapsed ovarian (fallopian tube / primary peritoneal) and endometrial (uterus) clear cell carcinomas with NO loss of ARID1A expression treated with AZD6738 in combination with olaparib.
• Experimental: 3: ceralasertib (AZD6738) + olaparib
  Women with other rare relapsed gynaecological cancers (endometrioid ovarian carcinoma, endometrioid endometrial carcinoma, cervical adenocarcinoma, cervical squamous, ovarian carcinosarcoma and endometrial carcinosarcoma) irrespective of ARID1A status, treated with AZD6738 in combination with olaparib.
• Experimental: 4: ceralasertib (AZD6738) + durvalumab
  Women with endometrial cancers (serous, clear cell, endometroid, carcinosarcoma) with ARID1A loss.
• Experimental: 5: ceralasertib (AZD6738) + durvalumab
  Women with endometrial cancers (serous, clear cell, endometroid, carcinosarcoma) with NO loss of ARID1A.

Primary Outcome Measure

Confirmed overall objective response rate (complete or partial response) as defined by RECIST version 1.1. [ Time Frame: From start of treatment until treatment discontinuation - minimum follow-up of 16 weeks (if not progressed earlier), up to max study period (estimated 36 months). ]