Background: The prognosis of chemorefractory GCT pts is dismal. Durva is an anti-PD-L1 monoclonal antibody (mAb). Treme is anti-CTLA4 mAb. We aimed to investigate the activity of Durva, alone or with Treme, in these pts. Methods: Apache (NCT03081923) is an open-label, randomized, 3-stage, phase 2 study. Pts who have failed ≥2 chemotherapy (CT) regimens receive Durva, 1.5 gr q4w, x 13 cycles (arm A) or Durva plus with Treme, 75 mg q4w, x 4 cycles, followed by Durva alone x total 13 cycles (arm B). Serum tumor markers (STM), and radiologic assessments are repeated q8 weeks. The primary endpoint is the modified objective response-rate (mORR = RECIST 1.1 complete or partial response [PR] or stable disease [SD]+STM reduction > 10%). H0: mORR rate ≤10%, H1: mORR ≥25%, type I and II error rates at 10%. The total sample size of 120 pts is split into 3 stages: in stage 1, according to Gehan’s rule, each arm is terminated whenever no response is observed. Biomarker analyses include: IHC PD-L1 expression on immune cells (Ventana SP142) and genomic sequencing with FoundationOne assay (Foundation Medicine Inc., Cambridge, MA, USA). Results of first stage are presented. Results: From 02/17-11/17, 18 pts were enrolled (17M, 1F), 9 per arm. 14 had gonadal and 4 extragonadal GCT, 15 had received ≥3 prior CT regimens. Median tumor mutational burden (TMB) was 4 mutations (mut)/mb. One pt (5.6%) had reversible G3 irAE (pneumonitis) in arm B. In arm A, 100% of pts had disease progression (PD), all with features of hyperprogression (hyper-PD): 4 had clinical PD and death before restaging, median increase in sum of tumor diameters (RECIST 1.1) was 146%, median increase in the elevated STM was 462%. In arm B, 2 responses (22.2%, 1 RECIST-PR in seminoma and 1 SD with STM reduction in nonseminoma) were observed. PD features were similar to arm A. PD occurred in both arms regardless of PD-L1 expression and TMB (PR case: PD-L1 negative and 4 mut/mb). Conclusions: Single-agent durvalumab should not be pursued further in GCT; conversely, combination immunotherapy showed signals of activity and will be expanded to 2^nd stage. Response biomarkers are urgently required. Clinical trial information: NCT03081923