The University of Georgia (Tbilisi)

Microbiomes are ecosystems, and their stability can impact the health of their hosts. Theory predicts that predators influence ecosystem stability. Phages are key predators of bacteria in microbiomes, but phages are unusual predators because many have lysogenic life cycles. It has been hypothesized that lysogeny can destabilize microbiomes, but lysogeny has no direct analog in classical ecological theory, and no formal theory exists. We studied the stability of computationally simulated microbiomes with different numbers of temperate (lysogenic) and virulent (obligate lytic) phage species. Bacterial populations were more likely to fluctuate over time when there were more temperate phages species. After disturbances, bacterial populations returned to their pre‐disturbance densities more slowly when there were more temperate phage species, but cycles engendered by disturbances dampened more slowly when there were more virulent phage species. Our work offers the first formal theory linking lysogeny to microbiome stability.

Aims Haemodynamic monitoring using implantable pressure sensors reduces the risk of heart failure (HF) hospitalizations. Patient self‐management (PSM) of haemodynamics in HF has the potential to personalize treatment, increase adherence, and reduce the risk of worsening HF, while lowering clinicians' burden. Methods and results The VECTOR‐HF I and IIa studies are prospective, single‐arm, open‐label clinical trials assessing safety, usability and performance of left atrial pressure (LAP)‐guided HF management using PSM in New York Heart Association class II and III HF patients. Physician‐prescribed LAP thresholds trigger patient self‐adjustment of diuretics. Primary endpoints include the ability to perform LAP measurements and transmit data to the healthcare provider (HCP) interface and the patient guidance application, and safety outcomes. This is an interim analysis of 13 patients using the PSM approach. Over 12 months, no procedure‐ or device‐related major adverse cardiovascular or neurological events were observed, and there were no failures to obtain measurements from the sensor and transmit the data to the HCP interface and the patient guidance application. Patient adherence was 91.4%. Using PSM, annualized HF hospitalization rate significantly decreased compared to a similar period prior to PSM utilization (0 admissions vs. 0.69 admissions over 11.84 months, p = 0.004). At 6 months, 6‐min walk test distance and the Kansas City Cardiomyopathy Questionnaire overall summary score demonstrated significant improvement. Conclusions Interim findings suggest that PSM using a LAP monitoring system is feasible and safe. PSM is associated with high patient adherence, potentially improving HF patients' functional status, quality of life, and limiting HF hospitalizations.

The research purpose This study aims to probe the internal consistency of survey questions aligning with priorities outlined in the World Economic Forum Insight Report "Unlocking the Social Economy" within Latvia and Georgia. It delves into the structural makeup of contemporary social entrepreneurs in these nations, their attitudes towards report priorities, and perceptions on fostering social economy development. Additionally, it explores how social entrepreneurship impacts Sustainable Development Goals (SDGs) like 11, 12, and 8, and proposes ways to enhance collaboration between public bodies and social economy actors in Latvia and Georgia. Design / Methodology / Approach The body of the survey was constructed according to the World Economic Forum Insight Report “Unlocking the Social Economy” priorities and the developed questionnaire was distributed in Latvia and Georgia from February to March 2024. The respondents were social entrepreneurs from both countries. The pilot study aimed to test the internal consistency of the survey`s questions. Findings underscore the role of social innovation in tackling contemporary development issues, and in fostering employment and economic growth. It delineates the modern social entrepreneur's profile in Latvia and Georgia, analyses their stance towards report priorities, solicits their views on actions vital for social economy growth. Originality / Value / Practical implications Social entrepreneurship is commonly recognized as an integral element of Catalyst 2030, a global movement of social entrepreneurs and social innovators looking to attain the SDGs by 2030. In particular, SDG 11 (Sustainable Cities and Communities), SDG 12 (Responsible Consumption and Production), and SDG 8 (Decent Work and Economic Growth) have been the most strongly impacted by sustainable entrepreneurship research. The research contributes to the process of unlocking the social economy towards an inclusive and resilient society more comprehensive for the social entrepreneurs and public bodies aiming to foster the development of the social economy. The main value of the research is revealing the need to update the relation of the public bodies of Georgia and Latvia to the interaction of social entrepreneurs.

LBA5515 Background: Batiraxcept is an Fc-fusion protein engineered to have a 200-fold higher affinity than wild-type AXL for its activating ligand GAS6. Batiraxcept sequesters GAS6 and inhibits its interaction with AXL. The Phase 1b study demonstrated safety with batiraxcept in combination with paclitaxel. Methods: This was a global, placebo-controlled, double-blind, phase III trial (ClinicalTrials.gov identifier: NCT04729608). Patients with PROC were randomly assigned 1:1 to receive intravenous batiraxcept every 2 weeks (D1, 15 every 28 days) with once-a-week IV paclitaxel (D1, 8, 15 every 28 days) or placebo with paclitaxel until disease progression. The primary endpoint was progression-free survival as assessed by investigator-assessed progression-free survival and secondary endpoint was overall survival. The randomization was stratified by platinum-free interval (< 3 months, 3 to 6 months), prior lines (1 to 2, 3 to 4), and prior bevacizumab status (yes, no). Exploratory endpoints include objective response rate, duration of response, quality of life, clinical benefit rate, and pharmacokinetic and pharmacodynamic profile. Results: A total of 366 participants were randomly assigned, and analysis was performed based on intent-to-treat. There were 183 participants who had prior bevacizumab and 177 with no prior bevacizumab. Median PFS (mPFS) was 5.13 months in the batiraxcept + paclitaxel arm and 5.49 months in the control paclitaxel arm, hazard ratio (HR) 1.29 (CI, 1.01 to 1.64; p=0.98). Median OS with batiraxcept + paclitaxel was 14.29 months versus 14.39 months, HR 1.06 (CI 0.77 to 1.46; p=0.64). Objective response rates (ORRs) per RECIST 1.1 were similar in both arms: 25.1% with batiraxcept + paclitaxel versus 26.2% with control paclitaxel arm. An exploratory analysis of the 304 evaluable tumors found that 61 (20%) of tumors had high AXL expression by immunohistochemistry (IHC). In participants with high tumor AXL expression, median PFS was 5.78 months in the batiraxcept + paclitaxel arm and 3.71 months in the control paclitaxel arm, HR 0.55 (CI, 0.31 to 0.98; p=0.042). For high AXL expressing tumors, median OS was 17.8 months in the batiraxcept + paclitaxel cohort and 8.11 months in the paclitaxel cohort, HR 0.32 (CI, 0.14 to 0.73; p=0.006). Conclusions: The addition of batiraxcept to paclitaxel did not improve PFS or OS. However, in AXL high tumors, the PFS and OS were higher in participants who received batiraxcept with paclitaxel compared to paclitaxel alone. Clinical trial information: NCT04729608 .

Objective The objective of the study was to understand the role of self-reported drinking behavior on liver health after achieving sustained viral response (SVR) among HCV patients. Results The study was conducted in HCV treatment provider clinics in three cities in Georgia: Tbilisi, Batumi, and Telavi. Face-to-face interviews were conducted using a questionnaire developed specifically for this study. 9.5% considered themselves heavy drinkers, while 94.2% were aware that heavy alcohol consumption can progress liver fibrosis. During treatment, 97.8% abstained from alcohol, while 76.6% reported resuming drinking after achieving SVR. Additionally, 52.1% believed that moderate alcohol intake is normal for individuals with low fibrosis scores. Liver fibrosis improvement was more prevalent among individuals who abstained from alcohol after HCV diagnosis (85.4% vs. 71.4%, p < 0.01) and after achieving SVR (87.5% vs. 74.7% of those who resumed drinking after achieving SVR, p < 0.02). In conclusion, the majority of HCV patients abstain from alcohol during treatment but resume drinking after achieving SVR. Those who abstain from alcohol intake after HCV cure have a higher chance of liver fibrosis improvement.

Recently, the mechanical performance of various mechanical, electrical, and civil structures, including static and dynamic analysis, has been widely studied. Due to the neuroma's advanced technology in various engineering fields and applications, developing small-size structures has become highly demanded for several structural geometries. One of the most important is the nano/micro-plate structure. However, the essential nature of highly lightweight material with extraordinary mechanical, electrical, physical, and material characterizations makes researchers more interested in developing composite/laminated-composite-plate structures. To comprehend the dynamical behavior, precisely the linear/nonlinear-free vibrational responses, and to represent the enhancement of several parameters such as nonlocal, geometry, boundary condition parameters, etc., on the free vibrational performance at nano/micro scale size, it is revealed that to employ all various parameters into various mathematical equations and to solve the defined governing equations by analytical, numerical, high order, and mixed solutions. Thus, the presented literature review is considered the first work focused on investigating the linear/nonlinear free vibrational behavior of plates on a small scale and the impact of various parameters on both dimensional/dimensionless natural/fundamental frequency and Eigen-value. The literature is classified based on solution type and with/without considering the size dependency effect. As a key finding, most research in the literature implemented analytical or numerical solutions. The drawback of classical plate theory can be overcome by utilizing and developing the elasticity theories. The nonlocality, weight fraction of porosity, or the reinforcements, and its distribution type of elastic foundation significantly influence the frequencies.

Context Ecosystem services provided by mountain forests are critically linked to forest structure. Social-ecological disturbance regimes (i.e., the rate, frequency, and patch size distribution of disturbances driven by interacting natural and anthropogenic processes) and land use affect forest structure, but their specific impacts are not fully understood. Objectives We examine how differences in disturbance regimes affect patterns of forest structure across three European mountain ranges with similar vegetation types but different land-use histories: the European Alps, the Carpathians, and the Caucasus. Methods We related data on horizontal and vertical forest structure, measured by spaceborne lidar (GEDI), with Landsat-derived information on forest disturbances (1986–2020) and topographic, climatic, and anthropogenic predictors. Results We found similar social-ecological disturbance regimes in the Alps and Carpathians (average annual disturbance rates of 0.34% and 0.39%, respectively, and median patch size < 0.5 ha), yet much lower disturbance rates and patch sizes in the Caucasus (0.08% yr⁻¹ and < 0.2 ha). Despite different disturbance regimes, we found similar patterns of forest structure. Two alternative states emerged consistently across all mountain ranges: a tall and closed-canopy state in 74–80% of forests and a low and open-canopy state (< 50% canopy cover) in the rest. While forest structure responded consistently to abiotic drivers such as topography and climate, its association with anthropogenic pressures differed between mountain ranges. Stand-replacing disturbances played an important role in the Carpathians, while forest structure in the Caucasus was related to proximity to settlements, reflecting local forest use. Conclusions Different social-ecological contexts in mountain regions can produce markedly different forest disturbance regimes. Despite these differences, similar states of forest structures emerge, suggesting strong attractors of structure in temperate mountain forests.

The issue of sexual violence that this article was tasked to deal with is neither new nor devoid of a regulating legislative framework. Moreover, a number of scientists from diff erent countries and institutions of the world have devoted their works to the topic under discussion, which has repeatedly been subjected to discussions in the European Court of Human Rights, International Criminal Court, and ad hoc tribunals. However, this article aspires to analyze the normative framework for the regulation of sexual violence in line with Article 36 of the Istanbul Convention in Germany and Georgia after the ratifi cation of the Convention in the last decade. The main focus of the study is the contentious interpretation of consent in sexual off ences. Due to the inevitable legislation reforms concerning sexual violence, this academic work examines new trends on regulating this issue in Western countries, especially in Germany, considering the historical ties of Georgian Criminal Code to German law. The article discusses sexual violence in general, providing a brief review of sexual violence legislation, where it is mainly presented by considering the international legal framework. Sexual violence and other sexual off ences according to Georgian and German criminal codes are presented in general terms and in a comparative manner. The article also explains rape in the light of its re-conceptualization, encompassing an analysis on sexual violence, including rape, especially in relation to consent. This, in turn, can prompt amendments to Georgian Criminal Code on the related issue, which currently does not comply with the standards on interpreting sexual violence, established by the Istanbul Convention and other important related international acts.

The term ‘digitalization’ of public administration, used as a synonym for ‘e-government,’ fi rst implies the implementation of fast, secure procedures by an administrative body. E-governance, or as it is more recently termed, digital governance, involves the introduction of innovations and technologies in public governance/administration. It can be argued that the digitalization of public administration against the background of contemporary social challenges may be the key of opportunities for both the state and members of the society. Despite its certain conditionality, the electronic governance index (since 2003, the United Nations has issued a comparative index of countries’ e-governance every two years, based on three main indicators) profi ciently reflects the dynamics of countries’ efforts in introducing innovations in public administration and involving citizens in the process of e-services, which ultimately contributes to bringing citizens closer to modern digital administration. The article refers to the legal aspects of using digital means in e-government on the example of Georgia. The reform of public administration in Georgia started in 2015, after the Association Agreement was signed between Georgia and the European Union. Georgia has already fulfi lled several commitments in the framework of this program in terms of striving for more transparent governance, but despite this, the mentioned reform faces challenges on this path. The article examines aspects of e-government such as e-services, e-participation, personal data protection, and the impact of e-government implementation on the efficiency of public administration. Since the mentioned issue is complex in nature and extends in several directions, the article discusses the regulation of electronic administrative proceedings and the effectiveness of its use in the process of implementing public administration, stages of modernization of state governance, types of electronic proceedings, possibilities of legitimate governance from the administrative body, and prospects for its implementation on the example of Georgia.

On March 29, 2022, the Parliament of Georgia passed the Law on Protection of Consumer Rights, with its primary provisions taking effect on June 1, 2022. By enacting the Law, Georgia has largely fulfilled its commitment under the Association Agreement with the European Union (EU) to implement EU directives governing consumer protection into its national legislation. However, it is essential to recognize that this reform marks just the initial phase of approximation. Challenges persist, especially in relation to European directives concerning the regulation of the digital marketplace. This article aims to provide a concise overview of the reform facilitated by the adoption of the new Law. Moreover, given that only one year has passed since the implementation of the Law, there remains a lack of practical experience or judicial precedent to assess its positive or negative impacts. Academic studies in this direction are also lacking. Consequently, the discussion in this article primarily centers on the novelty and challenges presented by the Law in the light of EU directives.

The 2017–2018 constitutional reform amended the Constitution of Georgia and changed the political system of the country. The president has the responsibility to represent the country in international relations, but only with the approval of the government. Constitutional norms are not specific, leaving room for different interpretations. Article 78 of the Constitution obliges constitutional bodies to use all measures for European integration. Under this constitutional obligation, the president met with European colleagues, though without governmental approval. This provoked the ruling party to initiate the process of impeachment. The Constitutional Court of Georgia concluded that the president breached the Constitution, but the parliament could not impeach the president. The paper analyses the role of presidential representation in international relations and its constitutional responsibility in the light of Georgia’s European aspirations.

In this article, we use an extended hybrid multitransmission line (MTL)/method of moments (MoM) approach for analyzing the diesel common-rail distribution system model installed in a perfect electrically conductive automotive vehicle and its interaction with an EMC wideband antenna in the 20–200 MHz frequency band. The proposed workflow involves analyzing the impedance of a discontinuity, such as changes in geometry or materials, in the cable system using a full-wave MoM solver. The impedance is then included in the MTL circuit model by introducing lumped element impedance at the boundary between different regions of the cable system. The extended hybrid MTL/MoM approach has higher accuracy and better predicts the EMC behavior of the system. Its accuracy, efficiency, and flexibility make it a promising solution for future automotive EMC challenges.

e13512 Background: The efficacy of curative-intent chemoradiation in treating cervical cancer is intricately tied to patient adherence to treatment protocols, often influenced by quality of life. In many areas of the world, treatment centers are often located far from where patients live. We sought to evaluate the impact of distance from the hospital and the quality of life on radiation adherence, especially for patients in the Country of Georgia. Methods: A prospective study conducted at Todua Clinic, Tbilisi, Georgia, from May 2023 - January 2024, involved locally advanced cervical cancer patients undergoing chemoradiation. The study was reviewed by the Todua Clinic Research Ethics Board. The questionnaire was offered at a baseline, at a radiation consult. Quality of life was assessed using the Functional Assessment of Cancer Therapy–Cervical Cancer Version 4. Distance categories (50-100km, 100-200km, 200-300km) were measured, and patient information was extracted from medical records. Radiation nonadherence was defined as missing ≥2 days of external beam radiotherapy. Inclusion criteria comprised stage II and III cervical cancer, prescribed chemoradiation therapy, and rural residency. Multivariable logistic regression was performed to control for confounding variables. Results: Out of the total 50 patients who were asked to participate, 22 declined (reasons for declining: 35% -no mood, 15% - too tired, 45% - not interested, 5% found questions inappropriate to answer) and 28 (56%) participated. 53% of patients were deemed adherent to the prescribed treatment. Statistical analyses unveiled an intriguing trend where mean adherence rates increased with distance from the hospital. However, the Chi-squared test yielded a p-value of 0.065, indicating a marginal significance. The breakdown of mean adherence rates by distance revealed 30.8% for 50-100 km, 66.7% for 100-200 km, and 83.3% for 200-300 km. Educational levels did not significantly impact treatment adherence, despite lower educational attainment in more distant rural areas. The analysis of Quality of Life (Score S) exhibited a negative coefficient (-0.01639), suggesting a subtle decrease in the likelihood of treatment adherence as Quality-of-Life scores increased. Conclusions: This study unveils the interplay between living distance, Quality of Life, and radiation adherence in locally advanced cervical cancer patients in the Country of Georgia. Our findings are interesting because, unlike in other countries where adherence tends to drop as distance increases, we noticed that adherence rates went up when patients lived farther away. One possible reason for this is that some patients move temporarily to cities like Tbilisi just for their radiation treatment. However, we recognize the need for a larger group of people to make our results more reliable and better understand their significance.

e23172 Background: Ovarian function suppression (OFS) is recommended for premenopausal patients with hormone (HR) positive early breast cancer at higher risk of recurrence. This is achieved with the use of the luteinizing hormone–releasing hormone agonist (LHRH) or oophorectomy. Sexual health is an important aspect for women with breast cancer, although unfortunately this issue is often not addressed. The aim of this study was to explore sexual health issues in premenopausal HR-positive patients with LHRH vs. Oophorectomy. Methods: A prospective observational study was conducted during the period of June 2023 and December 2023, enrolling premenopausal patients with Early stage HR positive (HER2 positive or negative) breast cancer diagnosed between 2017 and 2023, who were treated with OFS and remained free of disease. Involved patients were divided in two groups: Group A – received LHRH and Groups B - underwent oophorectomy. All patients were surveyed with EORTC QLQ-BR-45 questionnaire during their follow-up or scheduled LHRH injection visits at clinic. The questionnaire included Functional (F) and Symptom (S) scales evaluating sexual functioning, sexual enjoyment, endocrine therapy symptoms, endocrine sexual symptoms. Results: It was planned to enroll 100 patients in the study, but only 34 patients (24 in Group A, 10 in Group B) consented to participate, the majority of patients did not want to share their sexual life issues, even anonymously. Of those enrolled, median age was similar (42 in group A, 43 in group B), all had stage I-II breast cancer, and all were in continued remission at the time of enrollment. A similar proportion had HER2 positive disease (25% and 20%, respectively). Far more people in Group A were treated with breast conserving surgery (67% vs 30%, respectively) with 20% of participants in in Group B undergoing bilateral mastectomy. More volunteers received chemotherapy in Group A (88% vs 60% in group B). Among those in Group B, 6 of 10 were previously treated with LHRH before oophorectomy and the procedure was done due to endometrial hyperplasia (n = 3), known BRCA mutation (n = 1), persistent estrogen levels despite LHRH (n = 1), and patient preference (n = 5). More patients had a partner at enrollment in group B (90% vs 67% in Group A); only one person identified as a lesbian (enrolled in group B). F score S > 60 was noted in more Group A vs Group B participants (50% vs 30%). More people in Group A had S score S < 40, indicating higher quality of life (79% vs 50%, respectively). Conclusions: The study suggests that sexuality after cancer is a difficult area to study in Georgia, likely due to cultural issues. While we could not account for the contribution of known variables that impact sexuality in this population (e.g. surgery type, chemotherapy) due to small numbers, our data suggest that LHRH antagonist use may have a lesser risk to sexual function compared to oophorectomy.

An updated check-list of 69 species of Odonata occurring in the territory of the Republic of Belarus is presented in tabular form, indicating the presence of each species on the level of administrative regions (voblasc’). The data set for the check-list was created by compiling original data, records retrievable from available publications and databases, and those from museum collections. Contrary to current literature, due to a lack of reliable records, four Odonata species previously claimed for Belarus are not considered as being part of the Belarusian fauna, viz. Coenagrion ornatum, C. scitulum, Aeshna caerulea, and Somatochlora alpestris. Hitherto known records of Aeshna soneharai, a recently described new member of the European dragonfly fauna, are outlined. The history of discovery of rare species is critically reviewed. The flight period of each species is given in tabular form.

TPS8663 Background: Fianlimab (anti–lymphocyte activation gene 3 [LAG-3]) and cemiplimab (anti–programmed cell death-1 [PD-1]) are high-affinity, fully human, IgG4 monoclonal antibodies. In patients (pts) with advanced non-small cell lung cancer (aNSCLC) and programmed cell death-ligand 1 (PD-L1) expression ≥50% with no actionable mutations, first-line cemiplimab monotherapy showed significantly prolonged overall survival (OS) and progression-free survival (PFS) versus chemotherapy, with a safety profile consistent with previous reports for cemiplimab monotherapy. Despite pts’ selection by PD-L1 expression, only ~50% of pts respond to PD-1 therapy, thus there is a need for immune-oncology combinations like anti–LAG-3 plus anti–PD-1 to potentially improve outcomes. Methods: This is a randomized, double-blind, Phase 2/3 study (NCT05785767) to evaluate fianlimab + cemiplimab versus cemiplimab monotherapy as first-line treatment in pts with aNSCLC and tumors expressing PD-L1 ≥50%. The study will be conducted globally at ~210 sites. Key inclusion criteria: ≥18 years old; histologically confirmed squamous or non-squamous stage IIIB/C (not candidates for surgical resection or definitive chemoradiation) or stage IV NSCLC (no prior systemic treatment for recurrent or metastatic NSCLC); PD-L1 expression in ≥50% of tumor cells; ≥1 radiographically measurable lesion per Response Evaluation Criteria in Solid Tumors v1.1; Eastern Cooperative Oncology Group performance status ≤1; adequate organ and bone marrow function. This study has Phase 2 and Phase 3 parts and is expected to enroll ~850 pts. Pts will be treated for up to 108 weeks. In Phase 2, 150 patients will be randomized 1:1:1 into three treatment arms (Q3W IV): Arm A, fianlimab high dose + cemiplimab 350 mg; Arm B, fianlimab low dose + cemiplimab 350 mg; Arm C, cemiplimab 350 mg + saline/dextrose placebo. Based on findings from Phase 2, the dose of fianlimab (low or high) will be selected for Phase 3. In Phase 3, 700 patients will be randomized 1:1 into either experimental Arm A or B, and comparator Arm C (cemiplimab + placebo). In Phase 2, the primary endpoint is objective response rate (ORR) per blinded independent central review (BICR). The secondary endpoints are safety, ORR per investigator assessment, disease control rate (DCR), time to tumor response (TTR), duration of response (DOR), PFS, OS, patient-reported outcomes, pharmacokinetics, and immunogenicity. In Phase 3, the primary endpoint is OS in patients receiving fianlimab + cemiplimab versus cemiplimab monotherapy. Secondary endpoints are safety, ORR, DCR, TTR, DOR, and PFS, per BICR and investigator assessment, patient-reported outcomes, pharmacokinetics, and immunogenicity. This study is open for enrollment along with a second study of fianlimab + cemiplimab + chemotherapy in aNSCLC. Clinical trial information: NCT05785767 .

TPS8660 Background: Non-small cell lung cancer (NSCLC) is the most common type of lung cancer. Anti–programmed cell death-1 (PD-1) therapies have improved outcomes in patients with NSCLC; however, most patients do not respond or only respond for a limited time. The combination of cemiplimab (anti–PD-1) and chemotherapy has been studied for the first-line treatment of advanced NSCLC (aNSCLC), regardless of programmed cell death-ligand 1 (PD-L1) status. While the standard of care continues to evolve for NSCLC, one approach to potentially improve outcomes is the combination of checkpoint inhibitors (IO) with chemotherapy. Fianlimab (anti–lymphocyte activation gene 3 [LAG-3]) and cemiplimab are both high-affinity, fully human IgG4 monoclonal antibody IO therapies that have shown promising clinical activity when combined in patients with aNSCLC in a Phase 1 study (NCT03005782). This ongoing study will further investigate the combination of fianlimab + cemiplimab + chemotherapy. Methods: This is a randomized, multicenter, Phase 2/3 study of fianlimab + cemiplimab + platinum-doublet chemotherapy (chemo) versus cemiplimab + chemo in patients with unresectable stage IIIB/IIIC or stage IV NSCLC irrespective of PD-L1 expression levels (NCT05800015). This study will be conducted globally at approximately 210 sites. Patient eligibility criteria: ≥18 years old; squamous or non-squamous histology with stage IIIB, IIIC, or IV disease; valid PD-L1 result; ≥1 radiographically measurable lesion by computed tomography/magnetic resonance imaging; Eastern Cooperative Oncology Group performance status ≤1; adequate organ and bone marrow function. The Phase 2 portion will be used to determine the fianlimab dose selected for the Phase 3 portion: patients will be randomized 1:1:1 to receive fianlimab high dose + cemiplimab 350 mg + chemo (Arm A), fianlimab low dose + cemiplimab 350 mg + chemo (Arm B), or cemiplimab 350 mg + chemo + placebo (Arm C), Q3W IV. In Phase 3, patients will be randomized 1:1 into one of two treatment arms (either Arm A or Arm B, and Arm C) based on findings from Phase 2. The primary endpoint of Phase 2 is objective response rate (ORR) per blinded independent central review. The primary endpoint of Phase 3 is overall survival. The secondary endpoints include efficacy (ORR, disease control rate, time to tumor response, duration of response, progression-free survival, and overall survival), safety and tolerability, immunogenicity (anti-drug antibodies and neutralizing antibodies against fianlimab or cemiplimab in serum), patient-reported outcomes, and pharmacokinetics. This study and a parallel study of fianlimab + cemiplimab in patients with aNSCLC with tumors expressing PD-L1 ≥50% (NCT05785767) are currently open for enrollment. Clinical trial information: NCT05800015 .