Background: Early results with immune-checkpoint inhibitors (ICI) in NENs when used as single agents achieve limited response rates. Angiogenesis plays a key role in development and progression of NENs and synergism has been observed when antiangiogenics are combined with ICI in other tumors, whereas. We aimed to assess the efficacy and safety of cabozantinib (Cabo) plus atezolizumab (Atezo) in advanced and progressive NENs. Methods: CABATEN was a single-arm basket study using Atezo 1200 mg every 3 weeks plus Cabo 40 mg/day until progression or unacceptable toxicity in 6 NENs independent cohorts. We here focus in: well-differentiated lung neuroendocrine tumors (LungNET), pheochromocytoma paraganglioma (PPGL), well-differentiated gastroenteropancreatic (GEPNET) and grade 3 extrapulmonary neuroendocrine carcinomas (G3 EP-NEN). Primary endpoint was Overall Response Rate (ORR) by RECIST 1.1. The study had a Simon-II design. Here we present a subgroup analysis of efficacy for NENs (n=55), and for Cabo reduction using a relative dose intensity (RDI)<81% threshold and 3-month interval by Landmark analysis. Baseline characteristics were analyzed in subgroups with prolonged disease stability (PFS>12m or >15m) Results: Median (95%CI) age was 60 (56.0, 63.0) years and 62% were male. Cabo and Atezo treatment were administered for a median of 8.7m (95%CI: 6.2-11.9) and 9.0m (95%CI: 6.8-13.5) and interrupted due to AE’s in 80.0% and 40.0% of pts respectively. Cabo was reduced to 20 mg/day in 58,2% of patients. The 12-m PFS was 50% (95%CI: 29.6-84.4) RDI<81% vs 55.6% (95%CI: 39.7-77.9) RDI≥81% (p=0.9), 12-m OS was 86.7% (CI 95%: 71.1-100) RDI<81% vs 84.7% (CI 95%: 72.0-99.7) RDI≥81% (p=0.6), Cox. LungNET, PPGL, GEPNET and G3 EP-NEN presented a median PFS (m, 95% CI) of 8.4 [7.7-NR], 8.4 [5.7-NR], 13 [11.2-NR] and 2.7 [2.6-NR] respectively. PFS>12m subgroup had a trend towards better ECOG. PFS>15m GEP-NET presented a non-significant trend towards a lower Ki67 index and less previous treatment (no chemotherapy). ORR were 15.4% (95%CI:1.9-45.5) in PPGL and 16.7% (95%CI:4.7-37.4) in GEP-NET. LungNETs and G3 EP-NEN had no responses. Duration of response (DoR) were 12.2m (5.5-19.0) and 15.8m (10.6 - 20.2) in PPGL and GEP-NET cohorts, respectively. Conclusions: Cabo and Atezo showed limited activity but achieved prolonged disease control in a small group of patients with PPGL and GEPNET but not in LungNET and G3 EP-NEN, regardless of RDI of Cabo. Clinical trial information: 2019-002279-32.