Review of patient-reported outcomes in EMPOWER-Lung 1 in patients with advanced non-small cell lung cancer treated with cemiplimab versus chemotherapy.

Patient-reported outcomes following pembrolizumab or placebo plus pemetrexed and platinum in patients with previously untreated, metastatic, non-squamous non-small-cell lung cancer (KEYNOTE-189): a multicentre, double-blind, randomised, placebo-controlled, phase 3 trial.

First-line talazoparib plus enzalutamide versus placebo plus enzalutamide in men with metastatic castration-resistant prostate cancer and homologous recombination repair gene alterations: patient-reported outcomes from the randomised, double-blind, placebo-controlled, phase 3 TALAPRO-2 trial.

BackgroundIn the EMPOWER‐Lung 1 trial (ClinicalTrials.gov, NCT03088540), cemiplimab conferred longer survival than platinum‐doublet chemotherapy for advanced non–small cell lung cancer (NSCLC) with programmed cell death‐ligand 1 (PD‐L1) ≥50%. Patient‐reported outcomes were evaluated among trial participants.MethodsAdults with NSCLC and Eastern Cooperative Oncology Group performance status 0 to 1 were randomly assigned cemiplimab 350 mg every 3 weeks or platinum‐doublet chemotherapy. At baseline and day 1 of each treatment cycle, patients were administered the European Organization for Research and Treatment of Cancer Quality of Life‐Core 30 (QLQ‐C30) and Lung Cancer Module (QLQ‐LC13) questionnaires. Mixed‐model repeated measures analysis estimated overall change from baseline for PD‐L1 ≥50% and intention‐to‐treat populations. Kaplan–Meier analysis estimated time to definitive deterioration.ResultsIn PD‐L1 ≥50% patients (cemiplimab, n = 283; chemotherapy, n = 280), baseline QLQ‐C30 and QLQ‐LC13 scores showed moderate‐to‐high functioning and low symptom burden. Change from baseline favored cemiplimab on global health status/quality of life (GHS/QOL), functioning, and most symptom scales. Risk of definitive deterioration across functioning scales was reduced versus chemotherapy; hazard ratios were 0.48 (95% CI, 0.32‐0.71) to 0.63 (95% CI, 0.41‐0.96). Cemiplimab showed lower risk of definitive deterioration for disease‐related (dyspnea, cough, pain in chest, pain in other body parts, fatigue) and treatment‐related symptoms (peripheral neuropathy, alopecia, nausea/vomiting, appetite loss, constipation, diarrhea) (nominal p < .05). Results were similar in the intention‐to‐treat population.ConclusionsResults support cemiplimab for first‐line therapy of advanced NSCLC from the patient's perspective. Improved survival is accompanied by improvements versus platinum‐doublet chemotherapy in GHS/QOL and functioning and reduction in symptom burden.

Immune-Related Adverse Events and Outcomes in Patients with Advanced Non–Small Cell Lung Cancer: A Predictive Marker of Efficacy?

First-line talazoparib plus enzalutamide versus placebo plus enzalutamide for metastatic castration-resistant prostate cancer: patient-reported outcomes from the randomised, double-blind, placebo-controlled, phase 3 TALAPRO-2 trial.

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 .

IntroductionThere is potential clinical utility in using patient-reported outcomes (PROs) to predict survival in patients with advanced non-small cell lung cancer. We assessed the prognostic value of PROs for survival in two phase 3 cemiplimab studies in advanced non-small cell lung cancer.MethodsData from EMPOWER-Lung 1 and EMPOWER-Lung 3 Part 2, two global, randomized phase 3 clinical trials, were used. Patients with advanced non-small cell lung cancer and programmed cell death-ligand 1 expression ≥50% received cemiplimab monotherapy (n=283), and patients with no EGFR, ALK, or ROS1 genomic aberrations received cemiplimab plus chemotherapy (n=312). PROs were assessed using the European Organization for Research and Treatment of Cancer Core Quality of Life and Quality of Life Lung Cancer 13 questionnaires. Association between baseline PROs and survival was analyzed, and the C-statistic was used to assess the prognostic value of PROs in comparison with the Eastern Cooperative Oncology Group performance status (ECOG PS) scale.ResultsTwenty-five PROs were evaluated, of which 15 were significantly associated (P<0.05) with overall survival and were better predictors than ECOG PS. Fourteen PROs were significantly associated (P<0.05) with progression-free survival; of these, 13 had better prognostic value than ECOG PS. Patient-reported dyspnea and physical functioning had the highest prognostic values for overall survival (c=0.635 and c=0.619, respectively) and progression-free survival (c=0.593 and c=0.583, respectively). Stratifying physical functioning into high, medium, and low categories showed that patients with high physical functioning at baseline had significantly better overall survival (high vs low; HR, 0.41; 95% CI, 0.23-0.71; P=0.001), resulting in a 59% reduction in the risk of death. Similarly, patients in the high physical functioning category had significantly favorable progression-free survival (high vs low; HR, 0.44, 95% CI, 0.29-0.66; P<0.001) and a 56% reduction in the risk of death.ConclusionBaseline PROs, including dyspnea and physical functioning, have significant prognostic value for survival for patients with advanced non-small cell lung cancer.

Immune checkpoint inhibitors (ICIs) are standard-of-care for patients with advanced non-small cell lung cancer (aNSCLC) and programmed cell death-ligand 1 (PD-L1) expression ≥50%. A retrospective cohort study was conducted using the US de-identified electronic health record-derived Flatiron Health aNSCLC database (January 1, 2018, to July 31, 2021) among patients with PD-L1 ≥50% initiating first-line ICIs with or without chemotherapy. A clinical trial-like sub-cohort was also identified with Eastern Cooperative Oncology Group performance status 0-1, adequate organ function, and no brain metastases or other primary cancers. Kaplan-Meier methods were used to estimate time to treatment discontinuation, time to next treatment, progression-free survival and overall survival (OS) by ICI regimen (ICI+chemotherapy, ICI monotherapy) and PD-L1 expression (50-69%, 70-89%, 90-100%). Cox proportional hazard models were used to examine associations between ICI regimen, PD-L1 level, and OS, adjusting for baseline demographic and clinical variables. A total of 2631 patients with aNSCLC initiating ICI+chemotherapy (n = 992) or ICI monotherapy (n = 1639) were included; median (Q1, Q3) age was 71 (63-78) years and 51.6% were male. The trial-like sub-cohort (n = 1029) generally had better outcomes vs. the overall cohort. Patients receiving ICI+chemotherapy generally had longer median OS vs. ICI monotherapy. Multivariable analyses showed no association between ICI regimen and OS among patients with PD-L1 70-89% (hazard ratio [HR]: 0.90, 95% confidence interval [CI]: 0.73-1.09) or 90-100% (HR: 0.91, 95% CI: 0.77-1.08), but patients with PD-L1 50-69% receiving ICI+chemotherapy had longer OS (HR: 0.80, 95% CI: 0.64-0.99). Outcomes in real-world clinical trial-like patients with aNSCLC approached those reported in pivotal ICI trials in high PD-L1 expressers. ICI monotherapy offers a potential alternative in patients with PD-L1 ≥70% while avoiding potential chemotherapy toxicity exposure; the benefits are less clear in patients with PD-L1 50-69%. Future studies should confirm these findings.

IntroductionPembrolizumab stands as a first-line option for patients with advanced non-small cell lung cancer (NSCLC) and high programmed death-ligand 1 (PD-L1) expression (PD-L1 ≥50%). Several factors such as antibiotic exposure, low body mass index (BMI), certain metastatic location or poor performance status may influence outcomes.MethodsWe conducted a multicenter retrospective analysis in a cohort of patients with advanced high PD-L1 expression NSCLC treated with first-line pembrolizumab in clinical practice. We sought to evaluate clinical outcomes according to several factors.ResultsAmong the 494 included patients, median age was 67.29 years, 77% were male, 54% and 38% were former or current smokers, respectively; 84% had an Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0-1, and 48% had a BMI of <25. 32% of patients had bone metastases, 32% brain metastases and 16% liver metastases. 35% of patients had exposure to antibiotics (AB), 44% to corticosteroids and 62% to proton pump inhibitors (PPi). With a median follow-up of 14.3 months, the median overall survival (OS) and progression-free survival (PFS) were 15.9m (95% CI 13.1 to 18.8) and 9.9m (95% CI 7.7 to 12.1), and the overall response rate (ORR) was 43%. After univariate analysis, median OS in patients with ECOG-PS 0 vs. 1 vs. 2 was 36.7m vs. 14.8m vs. 2.7m (p<0.001). Median OS in patients who received treatment with corticosteroids vs. patients without exposure was 11.4m vs. 22.3m (p<0.001). After multivariate analysis, corticosteroid exposure (HR 1.41) and ECOG-PS (HR 2.40) maintained a prognostic impact.DiscussionFirst-line pembrolizumab outcomes in advanced high PD-L1 expression NSCLC patients could be negatively influenced by corticosteroid exposure or poor ECOG-PS.

TPS8117 Background: Co-blockade of lymphocyte activation gene 3 (LAG-3) and programmed cell death-1 (PD-1) may enhance the efficacy of anti–PD-1 therapies. Fianlimab (anti–LAG-3) and cemiplimab (anti–PD-1) are high-affinity, fully human, immunoglobulin G4 monoclonal antibodies. In a Phase 1 study (NCT03005782), fianlimab + cemiplimab showed promising clinical activity with durable responses and an acceptable risk–benefit profile in patients with programmed death-ligand 1 (PD-L1)-naïve, advanced NSCLC. Immuno-oncology + chemotherapy is a new standard of care in the perioperative setting, but potential improvements to outcomes in early-stage disease remain under investigation. Methods: This is a randomized, multicenter, double-blind, Phase 2 peri-operative study (NCT06161441) in patients with fully resectable stage II–IIIB (N2), operable, and treatment-naïve NSCLC with squamous or non-squamous histology. The aim of this study is to investigate the efficacy and safety of fianlimab + cemiplimab + chemotherapy versus cemiplimab + chemotherapy as peri-operative treatment. The study will be conducted globally at ∼130 sites. Key inclusion criteria: age ≥18 years; newly diagnosed, histologically confirmed, fully resectable stage II–IIIB (N2) NSCLC; no distant metastases; evaluable PD-L1 immunohistochemistry results; no cancer treatment in the past 3 years, except adjuvant hormone therapy for hormone-sensitive cancers in long-term remission; Eastern Cooperative Oncology Group performance status ≤1; no known EGFR mutations or ALK aberrations; and adequate organ and bone marrow function. Mediastinal lymph node sampling is required for patients with mediastinal adenopathy. Enrolled patients (n=∼180) will be stratified by clinical TNM stage (II vs III), histology (nonsquamous vs squamous), and PD-L1 expression (&lt;1%, 1–49%, ≥50%), and randomized (1:1:1) to the following study arms for the neoadjuvant period (≤4 cycles; each cycle is every 3 weeks): arm A, placebo + cemiplimab 350 mg + platinum doublet chemotherapy; arm B, fianlimab dose 1 + cemiplimab 350 mg + platinum doublet chemotherapy; arm C, fianlimab dose 2 + cemiplimab 350 mg + platinum doublet chemotherapy. After surgery, in the adjuvant period (≤14 cycles), patients in all arms will continue the same IO regimen with approved maintenance chemotherapy. Treatment will last ∼12 months (12 weeks’ neoadjuvant therapy + 42 weeks’ adjuvant therapy), or until disease recurrence, unacceptable toxicity, or a decision from the patient or investigator. Primary endpoint: pathological complete response as determined by blinded independent pathological review (BIPR). Key secondary endpoints: event-free survival and tumor response by investigator assessment, major pathological response by BIPR, safety, pharmacokinetics, immunogenicity, and patient-reported outcomes. Clinical trial information: NCT06161441 .

Health Related Quality of Life Results from the Open-Label, Randomized, Phase III Endeavor Trial Evaluating Carfilzomib and Dexamethasone Versus Bortezomib and Dexamethasone in Patients with Relapsed or Refractory Multiple Myeloma

Background: The real-world survival outcomes of first-line (1L) immunotherapy (IO)-based regimens for the treatment of advanced non-small cell lung cancer (aNSCLC) were assessed utilizing the Flatiron Health database from January 2011 to June 2023. Methods: Adult patients (pts) with aNSCLC receiving 1L IO monotherapy or single-agent IO + chemotherapy on or after January 1, 2016, were identified. Pts were excluded if they had EGFR/ALK mutations or unknown histological type. Overall survival (OS) and real-world progression-free survival (rwPFS) of 1L IO monotherapy and IO + chemotherapy were described using Kaplan-Meier analyses. Results: A total of 14,320 pts were included (5,166 pts receiving IO monotherapy; 9,154 pts receiving IO + chemotherapy). Among pts receiving IO monotherapy, the 1-, 2-, 3-, and 4-year OS rates were 52.3%, 36.5%, 27.4%, and 21.9%, respectively. The corresponding rwPFS rates were 29.2%, 17.5%, 12.7%, and 9.2%. Among pts receiving IO + chemotherapy, the 1-, 2-, 3-, and 4-year OS rates were 50.7%, 32.6%, 23.9%, and 19.2%. The corresponding rwPFS rates were 27.0%, 15.1%, 10.3%, and 7.8%. Table 1 presents the 4-year OS and rwPFS rates stratified by histological type, tumor programmed death ligand 1 (PD-L1) expression level, and Eastern Cooperative Oncology Group (ECOG) performance status. Patients with lower PD-L1 expression level (&amp;lt;1%), worse ECOG performance status (≥2), and squamous cell carcinoma had worse survival outcomes, regardless of the type of 1L treatment received. Conclusions: The real-world survival rates for patients with aNSCLC who were treated with 1L IO-based regimens were lower than those observed in pivotal trials, which indicates an unmet need for the management of newly-diagnosed aNSCLC. However, on average approximately 1 in 11 pts receiving IO monotherapy and 1 in 13 pts receiving IO + chemotherapy remained progression-free at the four year landmark and achieved an extended period of survival. Table: 4-year OS and rwPFS rates 1L IO monotherapy 1L IO + chemotherapy PD-L1 &amp;lt;1% PD-L1 ≥1-49% PD-L1 ≥50% PD-L1 &amp;lt;1% PD-L1 ≥1-49% PD-L1 ≥50% OS by histological type (sample size; 4-year rate, %) Squamous 122; 12.7 329; 14.0 814; 15.1 585; 11.7 647; 15.1 295; 23.3 Non-squamous 231; 16.7 516; 20.0 2563; 26.3 2263; 14.9 2058; 20.8 1313; 28.9 OS by ECOG performance status (sample size; 4-year rate, %) 0-1 193; 17.0 439; 20.8 1880; 27.6 1852; 16.8 1802; 21.9 1065; 28.0 ≥2 89; 6.7 261; 14.5 840; 12.7 478; 5.6 452; 11.1 241; 22.8 rwPFS by histological type (sample size; 4-year rate, %) Squamous 122; 7.6 329; 4.4 814; 6.8 585; 5.2 647; 8.3 295; 9.2 Non-squamous 231; 5.1 516; 10.0 2563; 11.2 2263; 4.3 2058; 6.3 1313; 14.7 rwPFS by ECOG performance status (sample size; 4-year rate, %) 0-1 193; 6.9 439; 10.4 1880; 11.9 1852; 5.4 1802; 6.8 1065; 14.5 ≥2 89; NA 261; 3.7 840; 5.0 478; 2.2 452; 3.9 241; 8.2 Citation Format: David Waterhouse, Saurabh Ray, Keith A. Betts, Sophie Gao, Yong Yuan, Manasvi Sundar, Shumin Rui, David Stenehjem. Real-world long-term survival outcomes of first-line immunotherapy-based regimens in advanced non-small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3819.

AK112, a novel PD-1/VEGF bispecific antibody, in combination with chemotherapy in patients with advanced non-small cell lung cancer (NSCLC): an open-label, multicenter, phase II trial

Health-related quality of life and symptoms in patients with previously untreated, locally advanced or metastatic non-squamous non-small cell lung cancer treated with sintilimab or placebo plus pemetrexed and platinum (ORIENT-11): A randomized, double-blind, phase 3 trial.