tbuckley/cabot-search huggingface dataset:
A multicenter, open label, randomized phase III study of atezolizumab with platinum-pemetrexed and with or without bevacizumab for patients with advanced nonsquamous non-small cell lung cancer (WJOG11218L APPLE Study).
Authors: Yoshimasa Shiraishi, Haruko Daga, Satoshi Ikeda, Akito Hata, Hideaki Mizutani, Tomohiro Sakamoto, Haruhiro Saito, Osamu Hataji, Hiroshi Tanaka, Atsushi Horiike, Hideo Saka, Tsuneo Shimokawa, Masahide Mori, Katsuya Hirano, Koichi Azuma, Tetsuya Mitsudomi, Takashi Seto, Nobuyuki Yamamoto, Kazuhiko Nakagawa, Isamu Okamoto
Journal: Journal of Clinical Oncology (2019)

TPS9125 Background: First-line treatment of non–small cell lung cancer (NSCLC) has undergone a paradigm shift to platinum combination therapy together with an immune-checkpoint inhibitor. Bevacizumab is expected to enhance not only chemotherapy but also the efficacy of immune-checkpoint inhibitors through blockade of vascular endothelial growth factor–mediated immunosuppression. The aim of this trial is to demonstrate an additional effect of bevacizumab administered together with platinum combination therapy and the immune-checkpoint inhibitor atezolizumab in patients with advanced nonsquamous NSCLC. Methods: Cytotoxic chemotherapy–naïve patients aged 20 years or older with a performance status of 0 or 1 are randomly assigned in a 1:1 ratio to receive either atezolizumab plus pemetrexed-carboplatin (APP) or atezolizumab, pemetrexed-carboplatin, and bevacizumab (APPB). Patients with genetic driver alterations such as those affecting EGFR or ALK are included if they have experienced disease progression or unacceptable side effects during treatment with at least one approved tyrosine kinase inhibitor. After four cycles of induction therapy, maintenance therapy with atezolizumab plus pemetrexed or with atezolizumab plus pemetrexed plus bevacizumab is administered for up to 2 years until evidence of disease progression or development of unacceptable toxicity. The primary end point is progression-free survival (according to central image review). Secondary end points are progression-free survival (determined by the attending physician), overall survival, response rate, response duration, and adverse events. Stratification factors are PD-L1 tumor proportion score (≥50% vs. &lt; 50%), stage, and driver gene alterations. We determined that, with a sample size of 350 patients (175 in each arm), the trial will have 80% power to show a hazard ratio for disease progression or death of 0.727 at a one-sided alpha level of 0.025 (as calculated on the basis of 311 such events) for comparison between the APPB and APP groups. Clinical trial information: 194565.
Alpelisib (ALP) + endocrine therapy (ET) in patients (pts) with <i>PIK3CA-</i>mutated hormone receptor-positive (HR+), human epidermal growth factor-2-negative (HER2-) advanced breast cancer (ABC): First interim BYLieve study results.
Authors: Hope S. Rugo, Manuel Ruiz Borrego, Stephen K. L. Chia, Dejan Juric, Nicholas C. Turner, Pamela Drullinsky, Florence Lerebours, Giulia Valeria Bianchi, Carolyn C. Nienstedt, Antonia Ridolfi, Astrid Thuerigen, Eva Ciruelos
Journal: Journal of Clinical Oncology (2019)

1040 Background: In the phase 3 SOLAR-1 study, ALP + fulvestrant (FUL) improved PFS in pts with HR+, HER2– ABC with a PIK3CA mutation overall and in the small group of pts with prior cyclin-dependent kinase 4/6 inhibitor (CDKi) use. We report interim data from the BYLieve study in pts with PIK3CA-mutated ABC and prior CDKi exposure. Methods: BYLieve is an ongoing, phase 2, open-label, non-comparative study of ALP 300 mg QD + ET in men and women with PIK3CA-mutated HR+, HER2– ABC whose disease progressed on/after CDKi + ET. Pts are permitted ≤2 prior anticancer therapies and ≤1 prior chemotherapy regimen for ABC. Pts with prior CDKi and AI ( FUL cohort) receive ALP and FUL 500 mg Q28d + C1d15 IM. Pts with prior CDKi and FUL ( LET cohort) receive ALP and letrozole (LET) 2.5 mg PO QD. In this preplanned interim analysis, conducted after ≥20 pts in FUL had ≥6 mo of follow-up, descriptive data are reported for preliminary safety and efficacy in the FUL and LET cohorts. Results: At data cutoff, 64 and 36 pts were enrolled in the FUL and LET cohorts, respectively; 39 pts ( FUL, n = 21; LET, n = 18) have safety and efficacy data with ≥6 mo follow-up and are reported here. Data on 100 pts enrolled at the time of data cutoff will be presented. In the 39 pts with ≥6 mo follow-up, median ALP duration was 5.3 and 5.5 mo in FUL and LET, respectively; median duration of FUL and LET was 5.6 mo. Median relative ALP dose intensity was 93% ( FUL) and 87% ( LET). Most common grade ≥3 adverse events were hyperglycemia (38.1% ( FUL) and 27.8% ( LET)) and rash (4.8% ( FUL) and 27.8% ( LET)). Only 2 pts (5%; 1 pt per cohort) discontinued due to an AE. In pts with centrally confirmed PIK3CA mutation (n = 20 ( FUL); n = 17 ( LET)), ORR was 20% ( FUL) and 18% ( LET), CBR was 40% ( FUL) and 35% ( LET). Efficacy and safety data for the 100 enrolled pts will be presented at the meeting. Conclusions: Pending further readout of the ongoing BYLieve trial, safety and tolerability of ALP and hormonal therapy in pts with prior CDKi are consistent with those of SOLAR-1; discontinuation due to toxicity was rare. NCT03056755. Clinical trial information: NCT02437318.
Novel correlates of protection against pandemic H1N1 influenza A virus infection
Authors: Sophia Ng, Raffael Nachbagauer, Angel Balmaseda, Daniel Stadlbauer, Sergio Ojeda, Mayuri Patel, Arvind Rajabhathor, Roger Lopez, Andrea F. Guglia, Nery Sanchez, Fatima Amanat, Lionel Gresh, Guillermina Kuan, Florian Krammer, Aubree Gordon
Journal: Nature Medicine (2019)
Molecular biology and treatment strategies for non-V600 BRAF-mutant NSCLC.
Authors: Marcelo Vailati Negrao, Victoria M. Raymond, Richard B. Lanman, Patrick Kwok Shing Ng, Rebecca Nagy, Kimberly Banks, Viola Weijia Zhu, Bianca E Amador, Emily Roarty, Young Kwang Chae, Jeffrey Melson Clarke, Jeffrey Crawford, Sai-Hong Ignatius Ou, David R. Gandara, John Heymach, Trever Grant Bivona, Caroline Elizabeth McCoach
Journal: Journal of Clinical Oncology (2019)

3102 Background: BRAF alterations (alts) account for ~4% of non-small cell lung cancers (NSCLC) with 50% being non-V600 alts. Because these alts are functionally heterogeneous and have a poorly characterized genomic landscape, determining appropriate treatment strategies is a challenge. Methods: The Guardant360 clinical database was queried for NSCLC patients (pts) with BRAF alts. Alts were categorized by clonality, type and class (1 and 2: BRAF monomer and dimer signaling; 3: requires co-occurring upstream RAS-mediated signaling). Functionality and drug screen assays were performed in Ba/F3 cells. Pts with non-V600 mutations were analyzed for sensitivity to MEK +/- BRAF inhibitors (M+Bi). Results: 306 unique BRAF alts were identified and the majority were observed once (233/306; 76%). Amplifications (806/1663; 48.5%) and missense alts (795/1663; 47.8%) were the most common occurrences. Missense alts were predominantly clonal (58%), and of known functionality (428/795; 54%). All class 1-2 alts were activating in Ba/F3 cells, while class 3 alts were found to have variable functionality (activating: 4/9). Functionality was correlated with clonality as demonstrated by class 1-3 alts having higher clonality compared to variants of unknown significance (VUS) (1: 56%; 2: 54%; 3: 45%; VUS: 38%; P&lt;0.01). Drug screens for G469V and L597R alts showed resistance to first generation BRAF inhibitors (IC50 ≥100nM), but sensitivity to M+Bi (IC50 0.02-36nM). Growth inhibition was more pronounced for dabrafenib + trametinib (D+T) (IC50 &lt;0.1nM) compared to encorafenib + binimetinib (IC50 8-35nM) and vemurafenib + cobimetinib (IC50 2-36nM). BRAF D594G mutation (class 3) was not activating in Ba/F3 cells. Three pts with non-V600 alts were treated with M+Bi. G469V and D594G had rapid disease progression (PFS 2 and 4 mos respectively), while pt with L597R has ongoing partial response (PFS 8+ mos). Conclusions: BRAF alts show correlation between clonality and functionality, which provides important clinical information given the numerous VUS in the BRAF non-V600 setting. Drug screens reveal non-V600 alts may be sensitive to M+Bi and suggest D+T is the most active combination. Clinical data supports that some non-V600 BRAF mutations may be sensitive to M+Bi.
Ph1/2 study of Rova-T in combination with nivolumab (Nivo) ± ipilimumab (Ipi) for patients (pts) with 2L+ extensive-stage (ED) SCLC.
Authors: Jyoti Malhotra, Petros Nikolinakos, Ticiana Leal, Jonathan Lehman, Daniel Morgensztern, Jyoti D. Patel, John M. Wrangle, Giuseppe Curigliano, Eric Dansin, Laurent Greillier, Melissa Lynne Johnson, Neal Ready, Gilles Robinet, Satwant Lally, Shekman Wong, Emin Avsar, Ricardo Valenzuela, Charity D. Scripture, Giovanni Selvaggi, Benjamin Besse
Journal: Journal of Clinical Oncology (2019)

8516 Background: Rovalpituzumab tesirine (Rova-T™) is an antibody-drug conjugate targeting DLL3, a Notch ligand expressed in SCLC but not normal tissue. Nivo ± Ipi has activity in 2L+ SCLC. Preliminary data suggest Rova-T may result in immunogenic cell death, complementing effects of Nivo ± Ipi. Methods: Eligibility: DLL3 expression (DLT phase only), progression after ≥1 line of therapy including a platinum-based regimen; ECOG 0-1; no prior immunotherapy. All pts received 0.3 mg/kg Rova-T IV on Day 1 of two 6-wk cycles. Cohort 1 (C1) also received two 3-wk cycles of 360 mg Nivo beginning on wk 4. Cohort 2 (C2) received four 3-wk cycles of 1 mg/kg Nivo and 1 mg/kg Ipi beginning on wk 4. Both cohorts then received 480 mg Nivo q4wks until PD. Primary objective: safety. Secondary: antitumor activity by RECISTv1.1, OS. Exploratory: PK. Results: As of Sep 7, 2018, 30 pts were dosed in C1 and 12 in C2. 55% were DLL3 high (≥75% DLL3 expression). 28 (67%) completed 2 planned cycles of Rova-T. 4 pts (1 in C1, 3 in C2) experienced DLTs including rash (3), pneumonitis (1) and colitis (1). C1 completed recruitment, and C2 enrollment was stopped after DLT evaluation phase. Preliminary PK showed Nivo±Ipi had no substantial effect on Rova-T exposure. Clinical trial information: NCT03026166. Conclusions: Despite activity in 2L+ ED-SCLC, Rova-T with Nivo/Ipi is not appropriate due to DLTs. Rova-T/Nivo demonstrated some durable responses; however, the safety data suggest that optimization of dose and schedule is warranted. NCT03026166.[Table: see text]
Alpelisib (ALP) with fulvestrant (FUL) in patients (pts) with <i>PIK3CA-</i>mutated hormone receptor-positive (HR+), human epidermal growth factor receptor-2-negative (HER2-) advanced breast cancer (ABC): Primary or secondary resistance to prior endocrine therapy (ET) in the SOLAR-1 trial.
Authors: Dejan Juric, Sibylle Loibl, Fabrice Andre, J. Ignacio Delgado Mingorance, Frederic Forget, Christelle Levy, Norikazu Masuda, Mario Campone, Pier Franco Conte, Hiroji Iwata, Ingrid A. Mayer, Hope S. Rugo, Celine Wilke, Antonia Ridolfi, Agnes Lteif, Eva Ciruelos
Journal: Journal of Clinical Oncology (2019)

1038 Background: A contributor to ETR, phosphatidylinositol 3-kinase (PI3K) pathway hyperactivation can result from mutations to PIK3CA; ~40% of pts with HR+, HER2– ABC exhibit tumors with this mutation. Use of the oral α-specific PI3K inhibitor ALP + FUL significantly improved progression-free survival (PFS) in pts with a PIK3CA mutation (HR 0.65; 95% CI, 0.50-0.85; P&lt;0.001) in SOLAR-1, which included both ET sensitive (ETS) and ETR pts (Table). ETS pts were later excluded by a protocol amendment. ETR was further defined as primary (1R) or secondary (2R) per ESMO criteria in both 1L and 2L pts. This subgroup analysis evaluated pts with a PIK3CA mutation based on tx line and endocrine status. Methods: SOLAR-1 was a phase 3, randomized, double-blind study of ALP 300 mg QD or PBO Q28d + FUL 500 mg Q28d + C1d15 in men and postmenopausal women with HR+, HER2– ABC whose disease progressed on/after an aromatase inhibitor. PFS was estimated by Kaplan-Meier method and median PFS (mPFS) presented by tx arm. A stratified Cox proportional hazards model estimated HR and 2-sided 95% CI. Results: Of 341 pts in the PIK3CA mutant cohort, 39 (11%) were ETS; 302 (89%) were ETR. mPFS in the ALP vs PBO arms was 22.1 vs 19.1 mo (HR 0.87; 95% CI, 0.35-2.17) for ETS pts and 9.4 vs 4.2 mo (HR 0.64; 95% CI, 0.48-0.84) for ETR pts. For ETR pts, mPFS for 1L (n=138) was 9.0 vs 4.7 mo (HR 0.69; 95% CI, 0.46-1.05) and for 2L (n=161) was 10.9 vs 3.7 mo (HR 0.61; 95% CI, 0.42-0.89). Conclusions: In SOLAR-1, mPFS was improved with ALP + FUL vs PBO + FUL across ETR pts in 1L and 2L. Representation of ETS pts was low in SOLAR-1, which included more ETR pts. Analysis of the PI3K pathway in ETS pts is warranted in future studies. Clinical trial information: NCT02437318. [Table: see text]
Targeted-sequencing in rare cancers and the impact on patient treatment.
Authors: Hitomi Sumiyoshi Okuma, Takashi Kubo, Hitoshi Ichikawa, Takashi Kohno, Takaaki Mizuno, Yuki Kojima, Kuniko Sunami, Akihiko Shimomura, Satoru Iwasa, Shunsuke Kondo, Yutaka Fujiwara, Kan Yonemori, Kenji Tamura, Noboru Yamamoto
Journal: Journal of Clinical Oncology (2019)

e14755 Background: Rare cancers lack standard or investigational therapeutic options. Next-generation sequencing (NGS) has provided new insight into personalized medicine. We sought to catalog genetic alterations detected from tissue NGS in rare cancers and to assess their clinical utility. Methods: This was a single-center series with patients (pts) who had been referred to the National Cancer Center Hospital (Tokyo, Japan). Patients with a metastatic/unresectable disease who underwent comprehensive genomic profiling of their tumor for the purpose of precision treatment were first identified (approved by the NCCH institutional review board). Among them, pts diagnosed as rare cancers, defined as an incidence of &lt; 6/100,000 pts/year, were included in this study. Prospectively consentedpts had tissue NGS testing (NCC Oncopanel) for point mutations, select indels, copy number amplifications, fusions. Alterations were assessed for incidence according to cancer type, functional impact, therapeutic implications. Results: Between July 2013 to April 2016, 289 pts were enrolled. 217 pts with sufficient tissue sample succeeded in sequencing. 78% (169/217) had a least one alteration most likely pathogenic. Most common alterations were TP53, PIK3CA, BRCA2, KRAS, MYC, ERBB2, RB1, CCND1, and ARID1A. 114/289 pts (39%) were classified as rare cancers: gynecological cancers (44 pts), cholangiocarcinoma (20), sarcomas (16), NET (9), thymic carc. (6), mesothelioma (3), CUP (2), urachal carc. (2), GIST (1), thyroid carc. (1), other super-rare cancers (10). 86 pts succeeded in sequencing; 72 % (62/86) had a variant most likely pathogenic. Most common alterations were TP53, KRAS, BRCA2, FBXW7, NF1, PIK3CA, ALK, BRCA1, and CCND1. 23 pts (27%) of rare cancer pts received a targeted drug of which 9 (10%) were “matched” to a detected alteration. Response rate to the “matched” therapy was CR/PR/SD/PD = 0/1/5/3 (ORR 11%). Conclusions: Genomic alterations were equally detected in rare cancers as well as common cancers, however showed different alteration profiles. Rare cancer pts receiving “matched” therapy and the response rate to those remain low, suggesting a need for a more efficient treatment development platform. Clinical trial information: UMIN000011141.
INTRAOCULAR LYMPHOMA DEVELOPED AFTER SALVAGE CHEMOTHERAPY FOR RECURRENT PRIMARY CNS LYMPHOMA AND PROMISING THERAPY-A CASE REPORT
Authors: Marlon G Saria, Courtney Corle, Jethro Hu, Jeremy Rudnick, Surasak Phuphanich, Maciej M Mrugala, Laura K Lee, Beverly D Fu, Daniela A Bota, Ryan Y Kim, Tiffany Brown, Homira Feely, Alexander Hu, Jan Drappatz, Patrick Y Wen, Jong W Lee, Bob Carter, Santosh Kesari
Journal: Neuro-Oncology (2011)

Author(s): Saria, Marlon G; Corle, Courtney; Hu, Jethro; Rudnick, Jeremy; Phuphanich, Surasak; Mrugala, Maciej M; Lee, Laura K; Fu, Beverly D; Bota, Daniela A; Kim, Ryan Y; Brown, Tiffany; Feely, Homira; Hu, Alexander; Drappatz, Jan; Wen, Patrick Y; Lee, Jong W; Carter, Bob; Kesari, Santosh
Prostate cancer with oligometastatic relapse: Combining stereotactic ablative radiotherapy and durvalumab, a randomized phase II trial (POSTCARD - GETUG-P13).
Authors: Stéphane Supiot, Vincent Libois, Valentine Guimas, Emmanuel Rio, Frederic Rolland, Emmanuelle Bompas, Damien Vansteene, Marine Tigreat, Albert Lisbona, Jeremy Colliaux, Loic Campion, Audrey Blanc-Lapierre
Journal: Journal of Clinical Oncology (2019)

TPS5088 Background: Following Stereotactic Body RadioTherapy (SBRT) targeting prostate cancer (PCa) oligometastasis, a tumor response assessed by PSA decrease is observed in a majority of case. To increase this tumor response, immune targeting agents can be combined with SBRT. We hypothesize that the anti-PDL1 agent Durvalumab will enhance immune response following SBRT targeting oligometastatic lesions. In this multicenter randomized phase II trial, we therefore propose to assess the comparative efficacy of SBRT with or without Durvalumab (MEDI4736) in oligometastatic recurrent hormone sensitive prostate cancer patients. Methods: Patients with PCa were eligible if they had a biochemical recurrence following treatment with curative intent, with a maximum of 5 bone or lymph node metastases, seen only on FCH-PET CT or Ga-PSMA PET CT, not seen on conventional imaging assessments (bone scan or thorax, abdomen and pelvis CT scan). Main exclusion criteria are serum testosterone level &lt; 8.5 nmol/ml, PSA doubling time less than 6 months, lung, brain, liver or other visceral metastases, any prior immune therapy. Patients were randomly assigned (2:1) to either SBRT + Durvalumab, or SBRT alone, with a stratification by investigation center, and number of metastases (1 vs 2-5). Durvalumab (1500 mg/cycle) will be started one month prior to SBRT to be able to evaluate PSA and immune response to the drug. It will be combined with SBRT (3x 9 or 3 x 11 Gy) and then given adjuvantly until progression with a maximum of 12 months. Ninety-six patients will be recruited in 15 centers over a recruitment period of 2.5 years. The primary endpoint is two-year Progression-free survival. Secondary objectives include quality of life, androgen deprivation therapy free survival, prostate cancer specific survival, overall survival, time to first symptomatic event, acute and late toxicity. Patients in both groups will be observed for PSA progression every 3 months after random assignment, with confirming imaging at PSA progression. Clinical trial information: NCT03795207.
Lenvatinib (len) plus pembrolizumab (pembro) for the first-line treatment of patients (pts) with advanced hepatocellular carcinoma (HCC): Phase 3 LEAP-002 study.
Authors: Josep M Llovet, Masatoshi Kudo, Ann-Lii Cheng, Richard S. Finn, Peter R. Galle, Shuichi Kaneko, Tim Meyer, Shukui Qin, Corina E. Dutcus, Erluo Chen, Leonid Dubrovsky, Andrew X. Zhu
Journal: Journal of Clinical Oncology (2019)

TPS4152 Background: Len, an inhibitor of VEGF receptors 1-3, FGF receptors 1-4, PDGF receptor α, RET, and KIT, is approved for first-line treatment of unresectable HCC (uHCC) based on the open-label phase 3 REFLECT study in which len showed noninferior overall survival (OS) and significantly improved objective response rate (ORR), progression-free survival (PFS), and time-to-progression (TTP) vs sorafenib. In the phase 2 KEYNOTE-224 study of pembro (a PD-1 inhibitor) as second-line treatment of advanced HCC, pembro showed meaningful clinical efficacy in pts previously treated with sorafenib, with median PFS 4.9 mo, median OS 12.9 mo, and a manageable safety profile. In results from the phase 1b KEYNOTE-524 trial, len+pembro was well-tolerated, with promising antitumor activity in pts with uHCC. LEAP-002 is a phase 3 study to evaluate the safety and efficacy of len+pembro vs len+placebo as first-line therapy for advanced HCC. Methods: Eligible pts are ≥18 y and have HCC confirmed by radiology, histology, or cytology; ECOG PS 0/1; BCLC stage C or stage B disease not amenable to locoregional therapy or curative treatment approach; CP class A liver score within 7 days before study; and ≥1 measurable lesion by RECIST v1.1. Pts with past or ongoing HCV infection and those with controlled HBV are eligible. 750 pts will be randomized 1:1 to receive len 12 mg (body weight [BW] ≥60 kg) or 8 mg (BW &lt;60 kg) orally once daily plus pembro 200 mg or placebo IV Q3W. Pembro and len will be administered until disease progression or unacceptable toxicity, with a maximum 35 cycles for pembro. Stratification will be by geographic region (Asia vs Japan and Western regions); macroscopic portal vein invasion or extrahepatic spread or both (yes or no); alpha fetoprotein ≤400 ng/mL vs &gt;400 ng/mL; and ECOG PS 0/1. Primary end points are PFS per RECIST v1.1 by blinded independent central review (BICR) and OS. Secondary end points are ORR, duration of response, disease control rate, and TTP per RECIST v1.1 by BICR, efficacy per modified RECIST, pharmacokinetics, and safety. Imaging assessments will be performed Q9W on study. AEs will be graded per CTCAE v4.0 and monitored up to 90 days after last dose. Clinical trial information: NCT03713593.
Immune checkpoint inhibitor response in tumors with LRP1B variants.
Authors: Jason Zhu, Matthew D Tucker, Chester Kao, Matthew Labriola, Sachica Cheris, Michael B. Datto, Yuan Wu, Patrick Healy, Santosh Gupta, Kedar Kirtane, Rajan T. Gupta, Daniele Marin, Tian Zhang, Megan Ann McNamara, Michael Roger Harrison, Daniel J. George, Andrew J. Armstrong
Journal: Journal of Clinical Oncology (2019)

e14291 Background: Low-density lipoprotein receptor-related protein 1B (LRP1B) is a putative tumor suppressor gene spanning &gt; 500 kb on chromosome 2. A melanoma study previously reported enrichment of LRP1B mutations in responders (34%) to immune checkpoint inhibitors (ICIs) compared with non-responders (3%). Deep deletions in LRP1B are frequently observed in non-small cell lung cancer (NSCLC, 12%), head and neck (11%), cervical (9%), bladder (8%), and prostate cancers (8%). This study examines the clinical response to ICIs in a diverse group of tumor types with LRP1B alterations. Methods: We conducted a single center retrospective study inclusive of all patients (pts) with tumors containing any LRP1B variant who were treated with an ICI between 01/2015 and 11/2018. The primary outcome of the study was to describe the clinical outcomes of patients with LRP1B alterations, with respect to radiographic response to therapy, time on therapy, duration of response, and overall survival. Results: 44 pts with an LRP1B variant were treated with an ICI at Duke between 01/2015 and 11/2018. The most common ICIs were pembrolizumab (29/44, 66%) and nivolumab (12/44, 27%). Tumor types included NSCLC (24/44, 55%), renal cell carcinoma (RCC, 5/44, 11%), and prostate cancer (5/44, 11%). 14 (32%) pts had pathogenic variants (PVs) and 30 pts (68%) had variants of uncertain significance (VUS). Among pts with LRP1b PVs, 36% (95%CI 14%-64%) had radiographic responses (5/14, 2 lung, 1 prostate, 1 RCC, 1 endometrial carcinoma), two of whom were MSI high. As a control, the radiographic response rate among patients with a LRP1b VUS was 10% (95%CI 3%-28%). Of those with PVs, 3 pts had stable disease, one of whom has been on CPI therapy for &gt; 22 months and 5 (36%) remain on therapy, with 2 (14%) pts discontinued due to immune toxicities, and 7 (50%) pts discontinued due to disease progression. The median TMB among responders was 12 (2-150.05 mut/Mb) and the median TMB amongst non-responders was 9.5 (6-18 mut/Mb). Conclusions: In a tumor agnostic population of pts harboring LRP1B PVs, 36% of pts have responses to ICI. The majority of responders were MSS and TMB low, which may suggest that PV in LRP1B may independently predict for response to ICI. Prospective and multicenter validation is now needed.