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Table 2 Study exclusion criteria

From: Precision medicine phase II study evaluating the efficacy of a double immunotherapy by durvalumab and tremelimumab combined with olaparib in patients with solid cancers and carriers of homologous recombination repair genes mutation in response or stable after olaparib treatment

Exclusion criteria
Step 1
  1 Patients involved in GUIDE2REPAIR study planning and/or conduct.
  2 Patients with EGFR, BRAF, ROS1 mutation or ALK rearrangement with lung small cell cancer and are not eligible.
  3 Patient eligible for another study of AstraZeneca Participation in another clinical study with an investigational product within 2 months prior to first olaparib administration.
  4 Administration of any anticancer therapy ≤21 days prior to the first dose of olaparib or 5 times its half-life, whichever smaller.
  5 Any unresolved toxicity NCI CTCAE Grade ≥ 2 from previous anticancer therapya.
  6 Any concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer treatmentb.
  7 Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation within 4 weeks of the first dose of study drugc.
  8 Major surgical procedure within 28 days prior to inclusion and patients must have recovered from any effects of any major surgery IP.
  9 Patients unable to swallow orally administered medication and patients with impairment of gastrointestinal (GI) function or GI disease that may significantly alter drug absorption of oral drugs.
  10 History of allogenic organ, bone marrow or double umbilical cord blood transplantationd.
  11 Active or prior documented autoimmune or inflammatory disorders.
  12 Uncontrolled intercurrent illness or patient considered at medical risk due to a serious, uncontrolled medical disorder or psychiatric illness/social situation that would limit study compliance, substantially increase risk of incurring AEs or compromise patient’s ability to give written informed consent.
  13 Currently taking medications with known risk of prolonging the QT interval or inducing “torsades de pointes”.
  14 Concomitant use of known strong or moderate CYP3A inducers.
  15 Resting ECG indicating uncontrolled, potentially reversible cardiac conditions, as judged by the investigator or patients with congenital long QT syndrome.
  16 Patients with myelodysplastic syndrome/acute myeloid leukemia or with features suggestive of MDS/AML.
  17 History of another primary malignancye.
  18 Patient with symptomatic central nervous system (CNS) metastases who are neurologically unstable or require increasing doses of corticosteroids or local CNS-directed therapy to control their CNS disease.
  19 History of active primary immunodeficiency and immunocompromised patients.
  20 Active infection.
  21 Current or prior use of immunosuppressive medication within 14 days before inclusion.
  22 Administration of live attenuated vaccine within 30 days prior to the first dose of IP.
  23 Female patients who are pregnant or breastfeeding or male or female patients of reproductive potential not willing to employ effective birth control.
  24 Known allergy or hypersensitivity to any of the study drugs or excipients.
  25 Prior treatment with any PARP inhibitor including olaparib or immunotherapy.
Step 2
  Patients should not enter the study if any of the exclusion criteria from STEP 1 and the following criteria for STEP 2 are fulfilled:
  26 Patient with progression observed on CT scan performed after 6 weeks of olaparib (STEP 1).
  1. a Except alopecia, ototoxicity, vitiligo, and laboratory values defined in inclusion criteria. Patients with Grade ≥ 2 neuropathy will be evaluated on a case-by-case basis after consultation with study physician. Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with olaparib or durvalumab or tremelimumab may be included only after consultation with study physician
  2. b Concurrent use of hormonal therapy for non–cancer-related conditions (e.g., hormone replacement therapy) is acceptable
  3. c Non-palliative radiotherapy within 21 days prior the first dose of study drug or within 6 weeks for therapeutic doses of MIBG or craniospinal irradiation. Palliative radiotherapy (which would be < 30% of the bone marrow) to non-target lesions is allowed
  4. d Patient with allogenic stem cell transplant within 3 months prior the first study dose of Olaparib are not eligible. Patient with myeloablative therapy with autologous hematopoietic stem cell rescue within 8 weeks of the first study drug dose are not eligible. Patients receiving any agent to treat or prevent graft-versus host disease ‘GVHD) post bone marrow transplant are not eligible for this trial
  5. e Except for: malignancy treated with curative intent and with no known active disease ≥5 years before the first dose of IP and of low potential risk for recurrence; adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease; adequately treated carcinoma in situ without evidence of disease and history of leptomeningeal carcinomatosis