Background: Papillary RCC accounts for 10-15% of kidney cancers and is the second most common subtype of RCC after clear cell RCC. HLRCC is a familial cancer syndrome characterized by a propensity for developing papillary kidney cancer. HLRCC-associated renal tumors are known to be clinically aggressive, with a paucity of treatment options. The combination of bevacizumab and erlotinib has shown promising activity in patients with HLRCC-associated RCC and sporadic pRCC (Srinivasan et al, ASCO 2020). We hypothesize that the addition of a PDL-1 inhibitor might provide synergistic clinical activity against these tumors. Methods: This is an ETCTN-sponsored, open-label, multicenter, phase 2 study evaluating bevacizumab, erlotinib and atezolizumab in adult and pediatric patients with advanced 1) HLRCC-associated RCC or 2) sporadic pRCC. Eligible patients will have cytologically or histologically confirmed advanced HLRCC- associated or sporadic pRCC, age ≥12 years, ECOG PS ≤2, no more than two prior regimens targeting the VEGF pathway, no prior treatment with PD-1 or PD-L1 inhibitors and adequate organ and marrow function. Patients with HLRCC-associated RCC or sporadic pRCC will be enrolled into parallel, independent cohorts. Initially, 12 adult patients with advanced HLRCC-associated RCC or sporadic pRCC will be enrolled into the safety run-in portion of the trial. If ≤ 3 dose-limiting toxicities are observed, enrollment will proceed into both cohorts and pediatric patients will be allowed to enroll. A Simon two-stage phase 2 minimax design will be used to determine accrual to each cohort. In the first stage, 12 evaluable patients will be enrolled into cohort 1) HLRCC-associated RCC or cohort 2) sporadic pRCC. If 0 of 12 patients have a CR, then no further patients will be enrolled in that cohort. If 1 or more of the first 12 evaluable patients enrolled have a clinical response, then accrual will continue until a total of 21 evaluable patients (adult or pediatric) have been enrolled into each cohort for a total of 42 patients. Adult patients will receive a fixed dose of bevacizumab (15 mg/kg IV every 21 days) plus atezolizumab (1,200 mg IV every 21 days) and erlotinib (150 mg PO daily). Pediatric patients will receive bevacizumab (15 mg/kg IV every 21 days) plus atezolizumab 15 mg/kg (max 1,200 mg IV every 21 days) and erlotinib 85 mg/m² (max 150 mg PO daily). The primary endpoint is to assess the complete response rate according to RECIST 1.1 in patients with advanced 1) HLRCC-associated RCC and 2) sporadic pRCC. Secondary endpoints include safety and tolerability, objective response rate, disease control rate, progression-free survival and overall survival. Key exploratory endpoints include evaluation of immunologic modulation associated with this regimen. The study has just opened to accrual. Clinical trial information: NCT04981509.