General step 1
1 Patients > 18 years at time of inclusion capable of giving signed informed consent.
2 Performance status ECOG of 0 or 1.
3 Life expectancy ≥6 months.
4 Body weight > 30 kg.
5 Patients diagnosed with a solid malignancy, histologically confirmed (see cohort specific inclusion criteria below).
6 Presence of mutation in homologous repair gene (BRCA1, BRCA2, PALB2, ATM, FANCA, FANCB, FANCC, FANCE, FANCF, CHEK2, RAD51, BARD1, MRE11, RAD50, NBS1, HDAC2), LKB1/STK11, INPP4B, STAG2, ERG, CHEK1, BLM, LIG4, ATR, ATRX, CDK12). Homozygote or heterozygote mutations and loss of heterozygosity of the second allele accepteda.
7 At least one lesion measurable as defined by standard imaging criteria for the patient’s tumor type (RECIST v1.1) that can be accurately assessed at baseline and suitable for repeated assessment.
8 Patients must have normal organ and bone marrow function.
9 Female and male with adequate contraception method.
10 For all oral medications patients must be able to comfortably swallow capsules.
11 Patients affiliated to a social security regimen or beneficiary of the same according to local requirements.
General step 2
12 CT Scan evaluation after 6 weeks of olaparib should present response or stable disease as defined by RECIST v1.1 criteria.
- 2nd line and after
- Non-small cell lung cancer.
- Must have progressed after at least a first line with platinum based therapy.
Head and neck cancerbd
- Must have progressed after at least a 1st line with platinum based therapy.
Metastatic endometrial cancerbd
- Progression after one prior systemic, platinum-based chemotherapy.
Clear cell renal cancerbd
- Must have progressed after at least a line with anti-angiogenic agent.
- Must have progressed after at least a line with FOLFIRINOX regimen and/or Gemcitabine based chemotherapy.
- Must have received at least one and no more than two lines of prior platinum-containing therapy and progressed after the most recent platinum therapy in a platinum-sensitive timeframe (more than 6 months from the last dose of platinum before randomization).
- -2nd line and after.
- Documented evidence of metastatic castration resistant prostate cancer (mCRPC).
- Ongoing therapy with LHRH analog or bilateral orchiectomy.
Must have progressed on prior new hormonal agent (enzalutamine or abiraterone) and taxane chemotherapy.