Academic literature on the topic 'Nagriamel'

Abstract Background: Safe, effective treatment options for advanced melanoma that progressed on a PD-1/PD-L1 inhibitor is an unmet medical need. Results of the phase 1b KEYNOTE-029 trial showed promising antitumor activity in advanced melanoma with pembro combined with a CTLA-4 inhibitor. This ongoing, open-label, multiarm phase 1/2 study (NCT03179436) evaluating the CTLA-4 inhibitor Qmab + pembro showed antitumor activity as first-line treatment for advanced NSCLC and for previously treated extensive-stage SCLC. Data from the efficacy expansion phase in pts with advanced melanoma that progressed on a PD-1/PD-L1 inhibitor are presented. Methods: Pts with unresectable stage III-IV melanoma and confirmed progressive disease (PD) per iRECIST within 12 wk of the last dose of a PD-1/PD-L1 inhibitor given alone or in combination for ≥2 doses (combinations with CTLA-4 inhibitors were not allowed) were randomly assigned (1:1) to receive Qmab 25 mg IV Q6W with or without pembro 400 mg IV Q6W; 100 pts in the Qmab + pembro arm and 40 pts in the Qmab monotherapy arm were planned for enrollment. Treatment in both arms was given for up to 18 cycles (~2 y) or until PD, toxicity, or pt withdrawal. Pts who had PD after ≥2 Qmab monotherapy cycles could crossover to Qmab + pembro. Tumor imaging was assessed Q9W to wk 54 and Q12W thereafter. Primary end points were safety and ORR by BICR per RECIST v1.1. Secondary and exploratory end points included DOR and PFS by BICR per RECIST v1.1 and OS. Results: 151 pts were enrolled (n = 111, Qmab + pembro; n = 40, Qmab monotherapy); median time from first dose to database cutoff was 7.7 mo. In all pts, median age was 64 y; 66% of pts were male, 33% had BRAF-mutant tumors, and 50% had elevated LDH. Treatment-related adverse events (TRAEs) were reported in 87 pts (78%) in the Qmab + pembro arm and 24 pts (60%) in the Qmab monotherapy arm; grade 3/4 TRAEs were reported in 16 pts (14%) and 3 pts (8%), respectively. The most common TRAEs were pruritus (26%), fatigue (14%), diarrhea (14%), and rash (13%). No treatment-related deaths occurred in either arm; 5% of pts discontinued because of TRAEs. Confirmed ORR was 9% (95% CI, 4.4-15.9) with Qmab + pembro (1 CR, 9 PRs) and 3% (95% CI, 0.1-13.2) with Qmab monotherapy (1 PR). Median DOR was not reached (NR; range, 2.0+ to 13.8+ mo) with Qmab + pembro. DOR was 1.9+ with Qmab monotherapy. Median PFS was 2.1 mo (95% CI, 2.1-3.2) with Qmab + pembro and 2.1 mo (95% CI, 2.1-2.5) with Qmab monotherapy; 6-mo PFS rates were 21% and 13%, respectively. Median OS was NR (95% CI, 11.2 mo to NR) with Qmab + pembro and 7.8 mo (95% CI, 6.3 to NR) with Qmab monotherapy; 6-mo OS rates were 74% and 73%, respectively. Conclusions: Qmab + pembro was generally well tolerated and provided modest antitumor activity in pts with advanced melanoma that progressed on a PD-1/PD-L1 inhibitor. This combination and a coformulation of Qmab + pembro will be further investigated in the KEYMAKER-U02 study. Citation Format: Sanjeev Deva, Jacek Mackiewicz, Stephane Dalle, Helen Gogas, Iwona Lugowska, Alfonso Berrocal, Alexander M. Menzies, Michele Maio, Adnan Nagrial, Karmele Mujika Eizmendi, Jean-Jacques Grob, Christian Caglevic, Megan Lyle, Juan Martin-Liberal, Rachel Altura, Yixin Ren, Anuradha Khilnani, Jobin Cyrus, Shabana Siddiqi, Michal Lotem. Phase 1/2 study of quavonlimab (Qmab) + pembrolizumab (pembro) in patients (pts) with advanced melanoma that progressed on a PD-1/PD-L1 inhibitor [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr CT557.

Abstract Background: The anti-TIGIT antibody vibo in combination with pembro was well tolerated across all doses in the dose-escalation phase of the ongoing phase 1 study in pts with advanced solid tumors (NCT02964013); promising antitumor activity of vibo + pembro was observed in anti-PD-1/PD-L1-naive NSCLC. We present initial results of the dose-expansion phase in pts with advanced cervical cancer naive to PD-1/PD-L1 inhibitors. Methods: Pts with histologically confirmed, locally advanced, or metastatic cervical cancer who failed prior standard-of-care chemotherapy or who experienced early progression on definitive chemoradiation and were naive to PD-1/PD-L1 inhibitors were randomly assigned 1:1 to receive 1 of 2 doses of vibo (200 or 700 mg) + pembro (200 mg) Q3W for ≤35 cycles (~2 y) or until PD, toxicity, or pt withdrawal. Primary end points were safety and tolerability. Secondary and exploratory end points included ORR, DOR, and PFS by investigator review per RECIST v1.1. Results: Median age of the 80 pts with cervical cancer was 49 y; 58% had an ECOG PS of 1; 53% received ≥2 prior lines of therapy; and 61% had PD-L1-positive tumors. 41 pts received vibo 200 mg, and 39 received vibo 700 mg. Median follow-up was 12 mo (range, 5-26). Treatment-related AEs (TRAEs) occurred in 27 pts in each treatment group (66%, vibo 200 mg; 69%, vibo 700 mg). The most frequent TRAEs (≥15%) were rash (22%), increased lipase (17%), and pruritus (17%) with vibo 200 mg + pembro and pruritus (28%), pyrexia (21%), rash (15%), and fatigue (15%) with vibo 700 mg + pembro. Grade 3 or 4 TRAEs occurred in 29% (vibo 200 mg + pembro) and 18% (vibo 700 mg + pembro). No deaths due to TRAEs were reported. Efficacy is reported in the Table. Conclusions: Vibo + pembro was safe in pts with advanced cervical cancer. Antitumor activity was comparable between the 2 doses of vibo studied and responses were observed irrespective of PD-L1 status. Based on these data, the RP2D for vibo remains 200 mg Q3W. Efficacy By Treatment Group By PD-L1 Statusa Vibo 200 mg + Pembro n = 41 Vibo 700 mg + Pembro n = 39 PD-L1-positive n = 49 PD-L1-negative n = 21 Confirmed ORR, % (95% CI) 15 (6-29) 23 (11-39) 20 (10-34) 14 (3-36) CR, n (%) 2 (5) 5 (13) 6 (12) 1 (5) PR, n (%) 4 (10) 4 (10) 4 (8) 2 (10) SD, n (%) 12 (29) 7 (18) 14 (29) 3 (14) PD, n (%) 18 (44) 19 (49) 20 (41) 12 (57) Median DOR, months (range)b Not reached (10 to 31+) Not reached (4+ to 35+) Not reached (4+ to 35+) Not reached (21 to 27+) Median PFS, months (95% CI) 2 (2-4) 2 (2-4) 4 (2-4) 2 (1-4) CR, complete response; DOR, duration of response; PD, progressive disease; ORR, objective response rate; PFS, progression-free survival; PR, partial response; SD, stable disease. aPD-L1 status was unknown in 10 patients; data were pooled across treatment groups. PD-L1 positivity was defined as combined positive score (CPS) ≥1 or when CPS was missing, as tumor proportion score ≥1% or mononuclear immune cell density score ≥2. b“+” indicates no PD present at the time of the last disease assessment. Citation Format: Ronnie Shapira-Frommer, Ruth Perets, Mark Voskoboynik, Kathryn Mileham, Adnan Nagrial, Brian Stein, Vincent Chung, Martin Gutierrez, Diana Chen, Tanya Keenan, Mohini Rajasagi, Jane Healy, Sun Young Rha. Safety and efficacy of vibostolimab (vibo) plus pembrolizumab (pembro) in patients (pts) with cervical cancer naive to PD-1/PD-L1 inhibitors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr CT508.

This thesis is an exploration of the ways in which past and present Churches of Christ worshippers from northern Vanuatu reflect on politik (Bislama: politics, political action but also much more). To comprehend what this term means to local people in Vanuatu, we must be aware of the contexts in which it is used, the events and relationships that are its exemplars and the local political economies of historical knowledge that inflect its meanings. To this end, this thesis explores the origins of politik as described by my interlocutors through oral histories about the interplay between their church, state institutions and Nagriamel, a traditionalist movement which emerged on Santo in 1967 and spread quickly throughout the northern New Hebrides. Through an examination of the content of these spoken histories, this thesis suggests that politik is seen to have corroded the unity of pre-existing social groups, such as the church, which is considered by its adherents to be indigenous. As a contingent state of democracy, politik describes the unwanted aspects of modernity and nationhood based on the perceived emergence of hierarchies between indigenous people in the post-colonial state of Vanuatu. Given that the rise of Nagriamel is considered to have inspired the resurgence of kastom where previously it was proscribed, kastom is often seen by conventional worshippers to be something to endure rather than celebrate. Among Churches of Christ worshippers, the conflict between kastom and church doctrine is considered to constitute part of the conflict inherent in politik.¶ Given that much of the knowledge on which this thesis was based was collected during interpersonal and group interviews, this thesis also explores the creation of political economies of historical knowledge about politik. Through a review of oral historical methodologies and appropriate anthropological theory, it examines the nature of information collected during participant-observation. As this thesis compares different genres of historical information (local, oral histories, national public histories and colonial archival records) it is also concerned with historical methodology.

This thesis is an exploration of the ways in which past and present Churches of Christ worshippers from northern Vanuatu reflect on politik (Bislama: politics, political action but also much more). To comprehend what this term means to local people in Vanuatu, we must be aware of the contexts in which it is used, the events and relationships that are its exemplars and the local political economies of historical knowledge that inflect its meanings. To this end, this thesis explores the origins of politik as described by my interlocutors through oral histories about the interplay between their church, state institutions and Nagriamel, a traditionalist movement which emerged on Santo in 1967 and spread quickly throughout the northern New Hebrides. Through an examination of the content of these spoken histories, this thesis suggests that politik is seen to have corroded the unity of pre-existing social groups, such as the church, which is considered by its adherents to be indigenous. As a contingent state of democracy, politik describes the unwanted aspects of modernity and nationhood based on the perceived emergence of hierarchies between indigenous people in the post-colonial state of Vanuatu. Given that the rise of Nagriamel is considered to have inspired the resurgence of kastom where previously it was proscribed, kastom is often seen by conventional worshippers to be something to endure rather than celebrate. Among Churches of Christ worshippers, the conflict between kastom and church doctrine is considered to constitute part of the conflict inherent in politik.¶ ...