Browsing by Author "Dizman, Nazli"

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    A phase II trial of sitravatinib + nivolumab after progression on immune checkpoint inhibitor in patients with metastatic clear cell RCC
    (Oxford University Press, 2025) Hahn, Andrew W.; Adra, Nabil; Vaishampayan, Ulka; Xiao, Lianchun; Dizman, Nazli; Yuan, Ying; Mukhida, Sagar S.; Campbell, Matthew T.; Gao, Jianjun; Zurita, Amado J.; Jonasch, Eric; Tannir, Nizar M.; Shah, Amishi Y.; Msaouel, Pavlos; Medicine, School of Medicine
    Background: Sitravatinib, an oral multi-kinase inhibitor targeting VEGFR, TAM, and MET, has been shown to resensitize the tumor microenvironment to immune checkpoint inhibitors (ICI) by reducing immune-suppressive myeloid cells in metastatic clear cell RCC (ccRCC). ICI is the standard first-line (1L) treatment of metastatic ccRCC, and there is unmet need for improved treatment outcomes after progression on ICI. We hypothesized that sitravatinib plus nivolumab would revert an immunosuppressive tumor microenvironment (TME) to improve clinical outcomes. Methods: In this investigator-initiated, phase II, multicenter trial (NCT04904302), patients with progressive metastatic ccRCC after 1-2 lines of treatment were enrolled into 3 cohorts: (1) 1L nivolumab + ipilimumab, (2) 1L pembrolizumab + axitinib, (3) prior cabozantinib or lenvatinib and ICI. Starting dose of sitravatinib was 100 mg PO daily and nivolumab was 480 mg IV every 4 weeks. The co-primary endpoints were objective response rate (ORR) and disease control rate (DCR) at 24 weeks. The study was designed to enroll 88 patients with an interim analysis for futility in each cohort using a BOP2 design, but it was terminated early due to discontinuation of sitravatinib development. Results: Fourteen patients were enrolled with 2 in cohort A, 6 in cohort B, and 6 in cohort C. Across all cohorts, the ORR was 15.4% (2/13, 1 not evaluable) and DCR at 24 weeks was 35.7% (5/14). DCR at 24 months was 63% for Cohort A + B and 0% for Cohort C. Median progression free survival was 5.5 mo [95% CI 3.8-not reached (NR)], and median overall survival was 13.3 mo (95% CI 8.77-NR). Six patients (42.9%) experienced a grade 3-4 adverse event (AE) and 2 patients (14.3%) experienced an immune-mediated AE. Conclusion: In this small phase 2 trial with limited sample size due to early termination, sitravatinib plus nivolumab demonstrated a manageable safety profile and produced modest clinical benefit. The observed responses occurred in patients who did not receive prior treatment with cabozantinib or lenvatinib.
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    Safety and Activity of Immune Checkpoint Inhibitors in People Living With HIV and Cancer: A Real-World Report From the Cancer Therapy Using Checkpoint Inhibitors in People Living With HIV-International (CATCH-IT) Consortium
    (American Society of Clinical Oncology, 2023) El Zarif, Talal; Nassar, Amin H.; Adib, Elio; Fitzgerald, Bailey G.; Huang, Jiaming; Mouhieddine, Tarek H.; Rubinstein, Paul G.; Nonato, Taylor; McKay, Rana R.; Li, Mingjia; Mittra, Arjun; Owen, Dwight H.; Baiocchi, Robert A.; Lorentsen, Michael; Dittus, Christopher; Dizman, Nazli; Falohun, Adewunmi; Abdel-Wahab, Noha; Diab, Adi; Bankapur, Anand; Reed, Alexandra; Kim, Chul; Arora, Aakriti; Shah, Neil J.; El-Am, Edward; Kozaily, Elie; Abdallah, Wassim; Al-Hader, Ahmad; Ghazal, Batool Abu; Saeed, Anwaar; Drolen, Claire; Lechner, Melissa G.; Drakaki, Alexandra; Baena, Javier; Nebhan, Caroline A.; Haykal, Tarek; Morse, Michael A.; Cortellini, Alessio; Pinato, David J.; Pria, Alessia Dalla; Hall, Evan; Bakalov, Veli; Bahary, Nathan; Rajkumar, Aarthi; Mangla, Ankit; Shah, Vishal; Singh, Parminder; Nana, Frank Aboubakar; Lopetegui-Lia, Nerea; Dima, Danai; Dobbs, Ryan W.; Funchain, Pauline; Saleem, Rabia; Woodford, Rachel; Long, Georgina V.; Menzies, Alexander M.; Genova, Carlo; Barletta, Giulia; Puri, Sonam; Florou, Vaia; Idossa, Dame; Saponara, Maristella; Queirolo, Paola; Lamberti, Giuseppe; Addeo, Alfredo; Bersanelli, Melissa; Freeman, Dory; Xie, Wanling; Reid, Erin G.; Chiao, Elizabeth Y.; Sharon, Elad; Johnson, Douglas B.; Ramaswami, Ramya; Bower, Mark; Emu, Brinda; Marron, Thomas U.; Choueiri, Toni K.; Baden, Lindsey R.; Lurain, Kathryn; Sonpavde, Guru P.; Naqash, Abdul Rafeh; Graduate Medical Education, School of Medicine
    Purpose: Compared with people living without HIV (PWOH), people living with HIV (PWH) and cancer have traditionally been excluded from immune checkpoint inhibitor (ICI) trials. Furthermore, there is a paucity of real-world data on the use of ICIs in PWH and cancer. Methods: This retrospective study included PWH treated with anti-PD-1- or anti-PD-L1-based therapies for advanced cancers. Kaplan-Meier method was used to estimate overall survival (OS) and progression-free survival (PFS). Objective response rates (ORRs) were measured per RECIST 1.1 or other tumor-specific criteria, whenever feasible. Restricted mean survival time (RMST) was used to compare OS and PFS between matched PWH and PWOH with metastatic NSCLC (mNSCLC). Results: Among 390 PWH, median age was 58 years, 85% (n = 331) were males, 36% (n = 138) were Black; 70% (n = 274) received anti-PD-1/anti-PD-L1 monotherapy. Most common cancers were NSCLC (28%, n = 111), hepatocellular carcinoma ([HCC]; 11%, n = 44), and head and neck squamous cell carcinoma (HNSCC; 10%, n = 39). Seventy percent (152/216) had CD4+ T cell counts ≥200 cells/µL, and 94% (179/190) had HIV viral load <400 copies/mL. Twenty percent (79/390) had any grade immune-related adverse events (irAEs) and 7.7% (30/390) had grade ≥3 irAEs. ORRs were 69% (nonmelanoma skin cancer), 31% (NSCLC), 16% (HCC), and 11% (HNSCC). In the matched mNSCLC cohort (61 PWH v 110 PWOH), 20% (12/61) PWH and 22% (24/110) PWOH had irAEs. Adjusted 42-month RMST difference was -0.06 months (95% CI, -5.49 to 5.37; P = .98) for PFS and 2.23 months (95% CI, -4.02 to 8.48; P = .48) for OS. Conclusion: Among PWH, ICIs demonstrated differential activity across cancer types with no excess toxicity. Safety and activity of ICIs were similar between matched cohorts of PWH and PWOH with mNSCLC.