Citations 2
Abstract CT136: Phase Ib study of siltuximab and spartalizumab in advanced pancreatic cancer
Gbolahan, Olumide B., Coleman, Kathleen, Cao, Yichun , Kane, Sujata , Craven, Sarah, Greene, Emily R. , McDonald, Andrew , Shaib, Walid L. , Akce, Mehmet , Diab, Maria , El‐Rayes, Bassel F. , El-Rayes, Bassel F , Gbolahan, Olumide B , Alese, Olatunji B. , Coleman, Kathleen M., Horvat, Natalie K. , Wu, Christina , Switchenko, Jeffrey M. , Lesinski, Gregory B
Cancer Research | April 5, 2024 | Volume: 84 | Issue: 7_Supplement | Pages: CT136-CT136
10.1158/1538-7445.am2024-ct136
Abstract Background: Pancreatic adenocarcinoma (PDAC) is an aggressive malignancy with dismal prognosis. Most patients present with advanced stages. Heightened levels of serum interleukin-6 (IL-6) are associated with carcinogenesis, immune suppression, and poor prognosis in PDAC. Preclinical data of dual inhibition of IL-6 and programmed death ligand-1 (PD-L1) facilitates CD8+ T-cell migration into pancreatic tumors and was effective in controlling tumor growth in syngeneic and genetically engineered PDAC mouse models. Siltuximab (Sil) is a chimeric monoclonal antibody which targets the IL-6 molecule specifically. Spartalizumab (Sparta) is a high-affinity ligand-blocking humanized IgG4 antibody against the PD-1 receptor. We developed a phase Ib/II trial to evaluate the safety, immunogenicity and preliminary antitumor activity of Sil and Sparta in metastatic PDAC (mPDAC). Methods: Patients (pts) with mPDAC who have progressed on at least one line of systemic chemotherapy were eligible for the trial. Other selected inclusion criteria were ≥18 years of age, ECOG PS 0-1 and measurable disease per RECIST v1.1. The phase Ib trial design is standard 3+3, with a primary endpoint of recommended phase II dose (RP2D). An additional 24 patients were planned for an expansion cohort. Sil was administered at escalating dose levels of 6 mg/kg (DL1) and 11 mg/kg (DL2), in combination with Sparta at 300 mg IV on day 1 of each 21-day cycle. Key secondary endpoints included overall response rate (ORR = CR + PR), progression-free survival (PFS) and overall survival (OS). Results: We enrolled 4 patients on DL1 and escalated to DL2/RP2D in the absence of a dose limiting toxicity (DLT). A total of 31 patients were subsequently treated at the RP2D (escalation + expansion). The median age was 68 years, 42% were male. Majority were White (63%) and 20% were Black. About 43% had head of pancreas primary tumors and 86% had liver involvement. The median number of lines of prior therapy was 3 (range 1-4). There was no objective response among the 4 patients on DL1; 1 had stable disease (SD) for 11 weeks as best response. 17 of 31 patients on RP2D had only a baseline assessment and came off study for progression of disease, prior to follow-up imaging assessment for response evaluation. Of the 14 RP2D patients with a follow-up assessment, ORR was 0% (3 were SD and 11 had progression of disease (PD) as best response), mPFS - 2.2 mos (95% CI: 1.9, 2.6), mOS - 5.5mos (95% CI: 2.8, 6.5). Treatment related adverse events (TRAEs) of any grade included fatigue (23%), anemia (18%), and increased liver enzymes (9.5%). There were no grade 4-5 TRAEs. Conclusions: The combination Sil/Sparta had an acceptable safety profile but did not elicit responses in advanced PDAC pts. Correlative studies using paired biopsies and blood are ongoing to determine how dual IL-6/PD-1 blockade impacts stromal and immune biomarkers in relationship to the clinical outcome measures. Funding and medications for the study were provided by Novartis and Recordati Rare Diseases Inc (NCT04191421) and NIH/NCI (R21CA266088). Citation Format: Olatunji B. Alese, Olumide Gbolahan, Kathleen M. Coleman, Yichun Cao, Sujata Kane, Sarah Craven, Emily Greene, Natalie Horvat, Andrew McDonald, Walid L. Shaib, Christina S. Wu, Mehmet Akce, Maria Diab, Jeffrey M. Switchenko, Gregory B. Lesinski, Bassel F. El-Rayes. Phase Ib study of siltuximab and spartalizumab in advanced pancreatic cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT136.
Social Determinants of Health and Redirection of Care for Infants Born Extremely Preterm
Bann, Carla , Vohr, Betty R. , McGowan, Elisabeth C. , Harmon, Heidi M. , Hintz, Susan R. , Duncan, Andrea F. , Polin, Richard A. , Laptook, Abbot R. , Mayne, Julie, Lamberson, Vita, Keszler, Mary Lenore, Hensman, Angelita M. , Vieira, Elisa , Pierre, Lucille St., Burke, Robert T., Alksninis, Barbara, Leach, Teresa M., Knoll, Andrea M., Moffat, Stephanie, Newman, Nancy S., Wilson-Costello, Deanne E. , Siner, Bonnie S., Friedman, Harriet, Truog, William E., Pallotto, Eugenia K. , Kilbride, Howard W. , Gauldin, Cheri, Holmes, Anne, Johnson, Kathy, Scott, Allison, Parimi, Prabhu S., Gaetano, Lisa, Merhar, Stephanie L. , Schibler, Kurt, Poindexter, Brenda B. , Cahill, Tanya E., Dudley, Juanita , Gratton, Teresa L., Grisby, Cathy, Henkes, Lisa, Kirker, Kristin, Stacey, Sara, Wuertz, Sandra, Cotten, C. Michael , Goldberg, Ronald N., Goldstein, Ricki F., Malcolm, William , Ashley, Patricia L., Mago-Shah, Deesha, Finkle, Joanne, Fisher, Kimberley A. , Gustafson, Kathryn E. , Bose, Carl , Bernhardt, Janice, Bose, Gennie, Clark, Cindy, Wereszczak, Janice, Warner, Diane, Talbert, Jennifer, Kicklighter, Stephen D. , Bentley, Alexandra, Edwards, Laura , Rhodes-Ryan, Ginger, Carlton, David P., Loggins, Yvonne, Adams‐Chapman, Ira , Bottcher, Diane I., Carter, Sheena L., Hale, Ellen C., Kendrick-Allwood, Salathiel, Laursen, Judith, LaRossa, Maureen Mulligan, Mackie, Colleen, Sanders, Amy , Smikle, Gloria V., Wineski, Lynn, Walsh, Michele C. , Bremer, Andrew A. , Higgins, Rosemary D. , Archer, Stephanie Wilson , Sokol, Gregory M. , Papile, L.A., Herron, Dianne E., Hines, Abbey C. , Lytle, Carolyn, Smiley, Lucy, Wilson, Leslie Dawn, Watkins, Donna, Gunn, Susan, Joyce, Jeff, Tyson, Jon E., Kennedy, Kathleen A. , Mosquera, Ricardo A. , Eason, Elizabeth, Stephens, Emily K. , Alaniz, Nora I., Allain, Elizabeth, Arldt-McAlister, Julie, Boricha, Fatima, Burson, Katrina, Garcia, Carmen, Hall, Donna J., John, Janice , Jones, Patrick M., Lillie, M. Layne, Mason, Carrie M., Martin, Karen , Martin, Sara C., McDavid, Georgia E., McKee, Shannon L. , Poe, Michelle, Rennie, Kimberly , Reddy, Tina, Rodgers, Shawna, Siddiki, Saba Khan, Sperry, Daniel K., Tate, Patti L. Pierce, Wright, Sharon L., Zanger, Dinorah, Jadcherla, Sudarshan R. , Timan, Christopher J., Luzader, Patricia, Batterson, Nancy, Baugher, Hallie, Beckford, Demi R., Burkhardt, Stephanie, Carey, Helen , Chao, Michelle, Cira, Courtney, Clark, Erna, DeSantis, Brittany, Fowler, Aubrey, Gutentag, Julie, Grothause, Jennifer L., Hague, Cole , Levengood, Katelyn, Marzec, Laura, McCool, Jacqueline, Miller, Bethany, Nelin, Mary Ann , Park, Courtney, Purnell, Jessica, Seabrook, Ruth , Shadd, Julie C., Small, Kristi , Stein, Melanie, Sullivan, Margaret, Sullivan, Rox Ann, Warnimont, Kyrstin, Yossef‐Salameh, Lina, Fearns, Erin, Wallace, Dennis, Auman, Jeanette O’Donnell , Gabrio, Jenna, Huitema, Carolyn M. Petrie , Zaterka-Baxter, Kristin M. , Meurs, Krisa P. Van , Chock, Valerie Y. , Stevenson, David K. , Ball, M. Bethany , Bahmani, Dona, Adams, Marian M. , Bentley, Barbara, DeAnda, Maria Elena, DeBattista, Anne M., Earhart, Beth, Huffman, Lynne C. , Krueger, Casey E., Lucash, Ryan E., Proud, Melinda S., Reichert, Elizabeth N., Weiss, Hali E., Williams, R. Jordan , Peralta-Carcelén, Myriam , Collins, Monica V., Cosby, Shirley S., Bailey, Kirstin J., Biasini, Fred J., Chopko, Stephanie A., Domnanovich, Kristy A., Jno-Finn, Chantel J., Ladinsky, Morissa, Moses, Mary Beth, Buie, Cindie, McNair, Tara E., Phillips, Vivien A., Preskitt, Julie , Rector, Richard V., Stringer, Kimberlly, Whitley, Sally, Chapman, Sheree York, Devaskar, Uday, Garg, Meena, Purdy, Isabell B., Chanlaw, Teresa , Geller, Rachel , Johnson, Karen, Eastman, Diane L., Walker, Jacky R., Goeke, Claire A., Schmelzel, Mendi L., Faruqui, Sarah E., Coulter, Brenda J., Schrimper, Bailey M., Jellison, Sydney S., Knosp, L.K., Arnold, Sandra J., Andrews, Haley A., Ellsbury, Dan L., Bass, Donia B., Tud, Tracy L., Baack, Michelle , Richards, Laurie A., Henning, Megan M., Elenkiwich, Chelsey, Broadbent, Megan, Muyden, Sarah Van, Brodkorb, Aimee, Watterberg, Kristi L. , Fuller, Janell, Ohls, Robin K. , Lacy, Conra Backstrom, Hartenberger, Carol, Beauman, Sandra Sundquist , Hanson, Mary, Lowe, Jean, Kuan, Elizabeth, Eichenwald, Eric C. , Abbasi, Soraya, Chaudhary, Aasma S. , Cucinotta, Dara M., Bernbaum, Judy, Gerdes, Marsha , Ghavam, Savin, Hurt, Hallam, Snyder, Jonathan, Ziolkowski, Kristina, Dhawan, Megan , Booth, Lauren, Catts, Christine, D’Angio, Carl T., Guillet, Ronnie , Myers, Gary J. , Reynolds, Anne Marie , Wadkins, Holly I.M., Sacilowski, Michael G., Jensen, Rosemary L., Merzbach, Joan, Zorn, William, Farooq, Osman , Maffett, Dee, Williams, Ashley, Hunn, Julianne, Guilford, Stephanie , Yost, Kelley, Rowan, Mary, Prinzing, Diane, Bowman, Melissa, Reubens, Linda J., Scorsone, Ann Marie, Harley-McAndrew, Michelle, Fallone, Caitlin, Binion, Kyle, Orme, Constance, Sabaratnam, Premini , Jones, Rachel , Boylin, Elizabeth, Rochez, Daisy, Li, Emily, Kachelmeyer, Jennifer , McKee, Kimberly G., Coleman, Kelly R., Moreland, Melissa, Cavanaugh, Brenna, Wyckoff, Myra H. , Heyne, Roy J. , Vasil, Diana M., Adams, Sally S., Chen, Lijun , Leon, Maria Magdalena, Duran, Joanne, Eubanks, Frances, McDougald, Rebecca, Pavageau, Lara, Sepulveda, Pollieanna , Guzman, Alicia, Harrod, M. J. E., Heyne, Elizabeth T., Madden, Linda A., Lee, Lizette E. , Puentez, Anna E., Tolentino-Plata, Kristine , Boatman, Cathy Twell, Vera, Azucena, Waterbury, Jillian, Yoder, Bradley A. , Baserga, Mariana , Faix, Roger G., Minton, Stephen D., Sheffield, Mark J., Rau, Carrie A., Baker, Shawna, Burnett, Jill, Christensen, Susan, Bledsoe, Laura Cole, Cunningham, Sean D. , Davis, Brandy, Elmont, Jennifer O., Hall, Becky, Jensen, Erika R., Loertscher, Manndi C., Marchant, Trisha, Maxson, Earl, McGrath, Kandace M., Mickelsen, Hena G., Morshedzadeh, Galina, Parry, Dilys M. , Reich, Brixen A., Schaefer, Susan T., Stout, Kelly, Stuart, Ashley L., Weaver-Lewis, Kimberlee, Winter, Sarah , Woodbury, Kathryn D., Osborne, Karen A., Bird, Karie, Coleman, Kathleen, Francom, Barbara L., Jordan, Jamie, Steffen, Mike, Tice, Katherine, Shankaran, Seetha , Natarajan, Girija , Pappas, Athina, Sood, Beena G. , Bajaj, Monika , February, Melissa, Agarwal, Prashant , Chawla, Sanjay , Bara, Rebecca, Childs, Kirsten, Woldt, Eunice, Goldston, Laura A., Wiggins, Stephanie A., Christensen, Mary, Carlson, Martha, White, Diane F., Baack, Michelle L , Brumbaugh, Jane E. , Bell, Edward F. , Travers, Colm P. , Carlo, Waldemar A. , Keszler, Martin , Watson, Victoria E. , Hibbs, Anna Maria , Kim, Jae Hong , Yolton, Kimberly , Russell, David G. , Laughon, Matthew Maxwell , White, Donna, Patel, Ravi M. , Stoll, Barbara J. , Sewell, Elizabeth , Maitre, Nathalie L. , (deceased), Jeff Joyce, Khan, Amir M , Rysavy, Matthew A. , Dempsey, Allison G. , White, Michelle, Sánchez, Pablo J. , Slaughter, Jonathan L. , Nelin, Leif Daniel , Yeates, Keith Owen , Fortney, Christine A. , Keim, Sarah A. , Newton, Julia L. , Pietruszewski, Lindsay , Das, Abhik , Gantz, Marie G. , Wiener, Laura Elizabeth , Crawford, Margaret M. , Newman, Jamie E. , Parlberg, Lindsay M. , Taylor, Heather Lee , Ambalavanan, Namasivayam , Colaizy, Tarah T. , Widness, John A. , DeMauro, Sara B. , Schmidt, Barbara Kristina , Kirpalani, Haresh Murli , Mancini, Toni, Lakshminrusimha, Satyan , Kent, Alison , Brion, Luc P. , Leon, Maria M. De, Harrod, Michelle, Parry, D. Melody, Coleman, Kathleen, Barks, John
JAMA Pediatrics | March 11, 2024 | Volume: 178 | Issue: 5 | Pages: 454
10.1001/jamapediatrics.2024.0125
ImportanceRedirection of care refers to withdrawal, withholding, or limiting escalation of treatment. Whether maternal social determinants of health are associated with redirection of care discussions merits understanding.ObjectiveTo examine associations between maternal social determinants of health and redirection of care discussions for infants born extremely preterm.Design, Setting, and ParticipantsThis is a retrospective analysis of a prospective cohort of infants born at less than 29 weeks’ gestation between April 2011 and December 2020 at 19 National Institute of Child Health and Human Development Neonatal Research Network centers in the US. Follow-up occurred between January 2013 and October 2023. Included infants received active treatment at birth and had mothers who identified as Black or White. Race was limited to Black and White based on service disparities between these groups and limited sample size for other races. Maternal social determinant of health exposures were education level (high school nongraduate or graduate), insurance type (public/none or private), race (Black or White), and ethnicity (Hispanic or non-Hispanic).Main Outcomes and MeasuresThe primary outcome was documented discussion about redirection of infant care. Secondary outcomes included subsequent redirection of care occurrence and, for those born at less than 27 weeks’ gestation, death and neurodevelopmental impairment at 22 to 26 months’ corrected age.ResultsOf the 15 629 infants (mean [SD] gestational age, 26 [2] weeks; 7961 [51%] male) from 13 643 mothers, 2324 (15%) had documented redirection of care discussions. In unadjusted comparisons, there was no significant difference in the percentage of infants with redirection of care discussions by race (Black, 1004/6793 [15%]; White, 1320/8836 [15%]) or ethnicity (Hispanic, 291/2105 [14%]; non-Hispanic, 2020/13 408 [15%]). However, after controlling for maternal and neonatal factors, infants whose mothers identified as Black or as Hispanic were less likely to have documented redirection of care discussions than infants whose mothers identified as White (Black vs White adjusted odds ratio [aOR], 0.84; 95% CI, 0.75-0.96) or as non-Hispanic (Hispanic vs non-Hispanic aOR, 0.72; 95% CI, 0.60-0.87). Redirection of care discussion occurrence did not differ by maternal education level or insurance type.Conclusions and RelevanceFor infants born extremely preterm, redirection of care discussions occurred less often for Black and Hispanic infants than for White and non-Hispanic infants. It is important to explore the possible reasons underlying these differences.