No abstract

5008 Background: LEN, a multikinase VEGFR inhibitor, plus everolimus is approved for advanced RCC after prior VEGF-targeted therapy. PEMBRO, an anti-PD-1 antibody, plus axitinib is approved as first-line therapy of advanced RCC. We report phase 2 results of the RCC cohort of a phase 1b/2 trial (Study 111/KEYNOTE-146) of LEN + PEMBRO in patients (pts) who progressed after ICI therapy. Methods: We performed a multicenter, open-label study of pts with mccRCC, who previously had disease progression by RECIST (confirmed ≥ 4 weeks later) during or following ICI therapy. Pts had measurable disease by immune-related RECIST, and ≥ 1 prior therapy. Pts received LEN 20 mg orally once daily plus PEMBRO 200 mg IV every 3 weeks until disease progression or toxicity. Tumor assessments were performed every 6 weeks (until week 24), then every 9 weeks. The primary endpoint was objective response rate (ORR) at Week 24 by irRECIST. Results: 104 pts were enrolled. At data cutoff (January 12, 2020), 71 (69%) pts were still on study treatment. Most pts had ≥2 prior anticancer regimens (58%). 91 of 104 pts were evaluable for response at Week 12 (13 pts NE at Week 12); 46 of 91 pts achieved a confirmed partial response for an ORR of 51% (Table). Median progression-free survival (PFS) was 11.7 months and median duration of response (DOR) was 9.9 months. The most common treatment-related adverse events (TRAEs) were fatigue (49%), diarrhea (44%), proteinuria (37%), hypertension (31%), nausea (31%), dysphonia (29%), stomatitis (29%), and arthralgia (27%). There was 1 grade 5 TRAE (upper gastrointestinal hemorrhage). 43% of pts required dose reduction and 12% of pts discontinued treatment due to TRAEs. Response and safety data will be updated to include all pts evaluable at an April 9, 2020 cut-off. Conclusions: LEN + PEMBRO demonstrated promising antitumor activity in pts with mccRCC with disease progression following ICI therapy. No new safety signals were detected. Efficacy outcomes by investigator review per irRECIST. Clinical trial information: NCT02501096 . [Table: see text]

No abstract

Background: NccRCC encompasses a heterogenous group of histologies comprising w25% of all RCC diagnoses with worse outcomes than ccRCC. Both C monotherapy and immune checkpoint inhibitors (ICIs) have shown preliminary activity in nccRCC, and several phase 2 trials are evaluating C in nccRCC. C promotes an immunepermissive environment which may enhance response to ICIs and has shown encouraging activity in combination with ICIs in tumor types including ccRCC, UC, mCRPC , and HCC. COSMIC-021, a multicenter phase 1b study, is evaluating the combination of C with A in various solid tumors (NCT03170960). We report initial results from cohort 10 in nccRCC.Methods: Eligible patients (pts) had ECOG PS 0-1 and had received 1 prior VEGFR-TKI therapy for advanced nccRCC. Prior ICI or C therapy was not allowed. Pts received C 40 mg PO QD and A 1200 mg IV Q3W. The primary endpoint is objective response rate (ORR) per RECIST v1.1 by investigator. Other endpoints include safety, duration of response (DOR), PFS, and OS.Conclusions: C + A demonstrated encouraging clinical activity in pts with nccRCC with an acceptable safety profile. Responses were observed in multiple histologies. Antitumor immunomodulatory effects were observed in peripheral blood with C + A.

Repeated rounds of faecal immunochemical testing (FIT) for occult blood is a common method for screening for colorectal cancer (CRC). However, the time interval between FIT rounds is not thoroughly investigated. In a CRC screening trial in South‐Eastern Norway, individuals were invited for biennial FIT between 2012 and 2019. The positivity threshold was >15 mcg haemoglobin/g faeces (mcg/g). Due to organizational challenges, the interval between screening rounds randomly varied between 1.5 and 3.5 years, forming a natural experiment. We investigated the detection rate of CRC and advanced neoplasia (AN: CRC or advanced adenoma) at the subsequent round (FIT2), according to the faecal haemoglobin concentration (f‐Hb) at the initial screening round (FIT1), and time between the two screening rounds. 18 522 individuals with negative FIT1 who attended FIT2 were included in this study. 245 AN were detected at FIT2, of which 34 were CRC. The CRC detection rate at FIT2 for participants with FIT1 = 0 mcg/g was 0.09% while it was 0.28% for participant with 0 > FIT1 ≤ 15 mcg/g; odds ratio (OR) 3.22, 95% CI 1.49‐6.95. For each 3 months' increment between FITs, the OR for detecting CRC was 1.33 (95% CI 0.98‐1.79), while the OR was 1.13 (1.02‐1.26) for AN. Individuals with FIT1‐value of 0 mcg/g, had a lower AN detection rate compared with participants with 0 > FIT1 ≤ 15 mcg/g, irrespective of time between tests. Although CRC and AN detection rates increase with increasing time interval between FITs, individuals with undetectable f‐Hb at first screen have substantially lower risk of CRC at the next screening round compared with individuals with detectable f‐Hb.