Health Net, LLC, a subsidiary of Centene Corporation, is an American health care insurance provider. Health Net and its subsidiaries provide health plans for individuals, families, businesses and people with Medicare and Medicaid.In July 2015, Centene announced it would acquire Health Net for $6.8 billion and completed its acquisition in March 2016.
This paper reconsiders knowledge sharing as a relational process of disorientation and reorientation, which is a way of turning toward others, the world, and possible futures. Drawing on an intergenerational participatory speculative design project in a historically Black neighborhood, we show how seniors and youth shared knowledge of turning toward the affective, more-than-human relations, as well as toward one another and collective futures. These practices reoriented participants across differences toward one another and their community, cultivating new cross-generational relationships and shared imagination. Building on Sara Ahmed’s notion of orientation and Black feminist thought, we argue that knowledge sharing is less about efficiency or productivity and more about relational alignment—negotiating how communities come together and move together toward otherwise futures. For HCI, this critical reframing foregrounds the racialized histories and everyday labors that sustain collective orientations, urging scholars and designers to consider how communities can collectively (re)orient themselves epistemically and ontologically through design, and what otherwise worlds those reorientations make possible.
ABSTRACTPurposeOsteoradionecrosis of the jaw (ORNJ) is a severe iatrogenic disease characterized by bone death after radiation therapy (RT) to the head and neck. With over 9 published definitions and at least 16 diagnostic/staging systems, the true incidence and severity of ORNJ are obscured by lack of a standard for disease definition and severity assessment, leading to inaccurate estimation of incidence, reporting ambiguity, and likely under-diagnosis worldwide. This study aimed to achieve consensus on an explicit definition and phenotype of ORNJ and related precursor states through data standardization to facilitate effective diagnosis, monitoring, and multidisciplinary management of ORNJ.MethodsThe ORAL Consortium comprised 69 international experts, including representatives from medical, surgical, radiation oncology, and oral/dental disciplines. Using a web-based modified Delphi technique, panelists classified descriptive cases using existing staging systems, reviewed systems for feature extraction and specification, and iteratively classified cases based on clinical/imaging feature combinations.ResultsThe Consortium ORNJ definition was developed in alignment with SNOMED-CT terminology and recent ISOO-MASCC-ASCO guideline recommendations. Case review using existing ORNJ staging systems showed high rates of inability to classify (up to 76%). Ten consensus statements and nine minimum data elements (MDEs) were outlined for prospective collection and classification of precursor/ORNJ stages.ConclusionThis study provides an international, consensus-based definition and MDE foundation for standardized ORNJ reporting in cancer survivors treated with RT. Head and neck surgeons, radiation, surgical, medical oncologists, and dental specialists should adopt MDEs to enable scalable health information exchange and analytics. Work is underway to develop both a human- and machine-readable knowledge representation for ORNJ (i.e., ontology) and multidisciplinary resources for dissemination to improve ORNJ reporting in academic and community practice settings.
8519 Background: Olomorasib, a potent, highly selective second-generation KRAS G12C inhibitor has demonstrated promising activity and a favorable safety profile in KRAS G12C-mutant NSCLC when combined with pembrolizumab. Here, we report updated results from LOXO-RAS-20001, a phase 1/2 trial (NCT04956640) of olomorasib, in patients (pts) with KRAS G12C-mutant NSCLC receiving olomorasib + pembrolizumab, and focus on pts receiving the combination as first-line (1L) therapy. Methods: Pts with advanced KRAS G12C-mutant NSCLC (tissue or plasma) in the 1L metastatic setting were eligible. Any PD-L1 level (0-100%) was permitted. Two dose levels of olomorasib (50 and 100 mg, orally twice daily) + pembrolizumab were evaluated. Adverse events (AE) were assessed across all treated pts; objective response rate (ORR) per RECIST v1.1 was assessed in pts with at least one post-baseline response assessment or who discontinued treatment before the first response assessment. Results: As of 13 November 2024, a total of 43 pts received olomorasib + pembrolizumab (50 mg, n=21; 100 mg, n=22) in the 1L setting with a median age of 70 years (range, 58-83); 10 (23%) were PD-L1 negative, 13 (30%) were PD-L1 1-49%, 19 (44%) were PD-L1 ≥50% and 1 (2%) was unknown. Median duration of follow-up was 5.5 months (range, 0.1-24.4). All grade TRAEs in ≥10% of pts (olomorasib- and/or pembrolizumab-related) were ALT/AST increased (33%/30%), diarrhea (28%), fatigue (16%), nausea (14%), pruritus (12%) and decreased appetite (12%); grade 3 TRAEs in ≥10% of pts were ALT/AST increased (26%/16%). Hepatic events were overall manageable with dose adjustments and/or corticosteroids. No pts had co-occurring total bilirubin increased or discontinued both study treatments due to hepatic events. Pneumonitis was reported in 2 pts (grades 2 and 4). The AE profile was generally comparable across doses. TRAEs led to olomorasib dose reduction in 16% of pts and discontinuation of combination treatment in 5% (2) pts. At time of data-cut, 33 pts remain on treatment and 10 discontinued. Among the 40 efficacy-evaluable 1L pts, at a median follow-up of 9 months (95% CI, 6-12), ORR was 70% (28/40; 95% CI, 54-83; 1 CR, 23 PR, 4 unconfirmed PR pending/ongoing) across all PD-L1 expression levels and disease control rate (DCR) was 90% (36/40; 95% CI, 76-97). In pts with PD-L1 ≥50%, ORR was 82% (14/17; 95% CI, 57-96) and DCR was 94% (16/17; 95% CI, 71-99). Median duration of response was not reached and progression free survival rate at 6 months was 80%. Conclusions: Olomorasib + pembrolizumab in the 1L metastatic setting demonstrated favorable safety and encouraging antitumor activity in pts with KRAS G12C-mutant advanced NSCLC across all PD-L1 expression levels. A global, registrational study investigating this combination in 1L NSCLC is currently enrolling (SUNRAY-01, NCT06119581). Clinical trial information: NCT04956640 .
Replication stress (RS) is a critical cancer vulnerability. ART0380 is an inhibitor of Ataxia-Telangiectasia and Rad3-related (ATR), the primary orchestrator of the cellular response to RS. This is the first clinical report of a development approach wherein tumor cells experience a triple combination of biological insults: induced RS by irinotecan, endogenous RS via ataxia-telangiectasia mutated (ATM) loss, and prevention of rescue from RS by ATR inhibition (NCT04657068). Patients (pts) with advanced cancers who had no satisfactory alternative treatment option received escalating doses of ART0380 (25mg to 400mg) on days 1-3 and 8-10 in combination with low dose irinotecan (60mg/m2 or 85mg/m2) on days 1 and 8 of a 21-day cycle. Pts in dose expansion were selected based on ATM protein expression. Key objectives included safety, tolerability, and preliminary efficacy. At the data cut-off (01Nov24), 87 patients were dosed with ART0380 + irinotecan. The recommended phase 2 dose (RP2D) was established as 200mg ART0380 on days 1-3 and 8-10 and 60mg/m2 irinotecan on days 1 and 8 of a 21-day cycle. At the RP2D (N=58), the median prior lines of therapy was 3 (range 1-7) with 59% of pts receiving prior irinotecan. The most common treatment related adverse events were neutropenia (53%), anemia (41%), fatigue (33%) and diarrhea (31%). Grade≥3 related diarrhea, nausea and vomiting each occurred in 1 pt. By intent-to-treat (ITT) analysis, the confirmed objective response rate (ORR) was higher in pts with ATM protein loss by immunohistochemistry compared to those with tumors that expressed ATM protein (see Table 1). Further analyses with longer follow-up will be available for conference presentation. ART0380 and low dose irinotecan is well tolerated and suitable for long-term dosing. Clinically meaningful activity has been demonstrated and further refined via biomarker selection (45% confirmed RECIST response rate in patients with ATM negative cancers). Susanna Ulahannan, Jason T. Henry, Kathleen N. Moore, Gerald S. Falchook, Meredith S. Pelster, Elisa Fontana, Bryony Harrop, Nicola Little, Helen Millward, Amelia Fielding, Sara Busacca, Emre Karakoc, Suraj Menon, Sarah V. Holt, Niall Martin, Graeme C. Smith, Desiree Headley, Ian C. Smith, Bert H. O'Neil, Babar Bashir. First results of ART0380 (an ATR kinase inhibitor) with low dose irinotecan in advanced or metastatic solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_2):Abstract nr CT267.
