Tx Cycles Research Articles

Abstract PO4-12-11: Patient (pt) time burden with IV vs subcutaneous (SC) administration of trastuzumab/pertuzumab (HP): A time and motion (T+M) substudy of a single arm phase II trial of adjuvant endocrine therapy plus HP for stage I HER2+ breast cancer

Abstract Background: The time required for in-clinic drug administration may have a substantial detrimental impact on breast cancer patients’ quality of life. SC drug administration, as opposed to IV, may reduce this time commitment. The purpose of this study was to estimate the relative difference in time and logistical burden between IV and SC administration of HP. Methods: We prospectively enrolled a pre-specified sub-cohort of pts participating on the ADEPT trial (NCT04569747) to this T+M substudy. The ADEPT trial is an ongoing single arm prospective phase II trial of adjuvant SC HP (for 1 yr) plus endocrine therapy for pts with hormone receptor-positive (HR+) and HER2+ stage I (pT1N0 or pT1N1mi) breast cancer. Pts eligible for ADEPT have completed primary breast surgery and are systemic therapy-naïve. Pts who received cycle 1 of loading SC HP at Dana-Farber Cancer Institute and tolerated SC drug administration were eligible and enrolled consecutively to the T+M substudy until the T+M accrual goal; accrual to the T+M substudy was mandatory for eligible pts. The T+M substudy was a single arm crossover design in which pts received 2 cycles of IV HP, followed by 2 cycles of maintenance dose SC HP. During those 4 treatment (tx) cycles, timepoints in the drug preparation and administration process were captured from the electronic medical record or flowsheets filled out by infusion nurses. The primary endpoint of the T+M substudy was total pt chair time in the infusion area (measured from start of first drug administration to end of final post-drug observation period). Exploratory endpoints included total drug preparation time and total pt tx experience time. A sample size of 22 pts was estimated to provide 86% power with 2-sided alpha 0.05 to detect a difference of 70 mins in the primary endpoint by tx arm (IV vs SC). For all endpoints, the average time across both tx cycles was calculated for each pt, and the overall mean across pts for each of IV and SC administration was computed (with standard deviation). Average times for IV vs SC administration were compared via paired Wilcoxon signed rank tests. Adjustments for multiple comparisons were not included. Results: 22 pts participated on the T+M substudy, and each had timepoints captured during 4 tx cycles (2 IV and 2 SC cycles), for a total of 88 patient-cycles analyzed overall. Pts had median age 58 yrs (range 42-83), and were 96% female, 82% White, 9% Black, 9% Asian; and 100% non-Hispanic. Comparison of time intervals for IV vs SC drug administration is shown in the Table. Mean total pt infusion chair time was 84.3 mins with IV HP, vs 22.5 mins with SC HP, for a difference of 61.8 mins shorter pt time commitment in favor of SC administration (p< 0.0001). The mean total drug preparation time was significantly decreased in favor of SC administration (by 78.2 mins; p< 0.0001); and the total pt tx experience time was significantly decreased in favor of SC administration (by 81.8 mins; p< 0.0001). Conclusions: This prospective T+M study demonstrated that pt infusion chair time is significantly decreased with SC as compared to IV administration of HP, shortening this pt time burden by approximately one hour. SC drug administration is an approach that may help to improve and shorten the pt breast cancer therapy experience and decrease pharmacy burden. Table. SD, standard deviation Citation Format: Adrienne Waks, Noah Graham, Emily Chen, Anna Mae Frey, Victoria Attaya, Ibrahim Abbass, Anita Fung, Jesse Sussell, Patricia Cortazar, Caroline Harvey, Kenneth Almeida, Denise Leth, Wendy Chen, Jose Leone, Susan Schumer, Nabihah Tayob, Sara Tolaney. Patient (pt) time burden with IV vs subcutaneous (SC) administration of trastuzumab/pertuzumab (HP): A time and motion (T+M) substudy of a single arm phase II trial of adjuvant endocrine therapy plus HP for stage I HER2+ breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-12-11.

Abstract CT243: Primary analysis of the Phase 2 ELM-2 study: Odronextamab in patients (pts) with relapsed/refractory follicular lymphoma (R/R FL)

Abstract Background: R/R FL is an incurable disease and outcomes worsen with successive relapses. A high unmet need remains for therapies that improve tumor control and extend survival after relapse. Odronextamab, an off-the-shelf CD20×CD3 bispecific antibody, demonstrated compelling efficacy, generally manageable safety, and maintenance of pt-reported overall quality of life scores from baseline in an interim analysis of the ELM-2 study (NCT03888105) in heavily pretreated pts with R/R FL (Villasboas et al. ASH 2023). Here, for the first time, we present the primary analysis of R/R FL in ELM-2. Methods: IV odronextamab was administered in 21-day cycles (C) until disease progression/unacceptable toxicity. Steroid prophylaxis and step-up dosing (0.7/4/20 mg) were used in C1 to mitigate the risk of cytokine release syndrome (CRS), followed by 80 mg on Days (D) 1, 8, and 15 of C2-4. Maintenance dosing continued at 160 mg Q2W, or Q4W if complete response (CR) was durable for 9 months (mo). Primary endpoint was objective response rate (ORR) per Lugano criteria by independent central review (ICR). Secondary endpoints included CR rate, duration of response (DOR), progression-free survival (PFS), and overall survival (OS). Primary analysis was performed when 128 pts had ≥52 weeks’ follow-up. Results: At data cutoff (Oct 20, 2023), 128 pts with FL Grade (Gr) 1-3a were evaluable for efficacy and safety: median age 61 yrs (range 22-84); FLIPI risk score 3-5 57.8%; POD24 49.2%; median 3 prior lines of therapy (2-13); 71.9% refractory to last treatment (Tx); 74.2% refractory to an anti-CD20 antibody. The median no. of Tx cycles was 19.4 (0.1-95.9); 95.3% and 85.2% of pts completed C1 and C4, respectively.Median efficacy follow-up was 20.1 mo; ORR was 80.5% and CR rate was 73.4% confirmed by ICR. Responses were durable (median DOR 22.6 mo; median DOCR 25.1 mo). Median PFS was 20.7 mo and 24-mo PFS was 46.1%. Median OS was not reached and 24-mo OS was 70.1%.The odronextamab safety profile was generally manageable and consistent with previous reports. Tx-emergent adverse events (AEs) occurred in all pts (Gr ≥3 85.9%); 15.6% had AEs leading to Tx discontinuation. With 0.7/4/20 mg step up (n=60), CRS events were mostly low grade (Gr 1 45.0%; Gr 2 10.0%; Gr 3 in 1 pt), occurred mostly in C1, and resolved in a median of 2 days; ICANS was reported in 1 pt (Gr 2). Infection rates were consistent with heavily pretreated, immunosuppressed pts (Leonard et al. JCO 2019; Hayne et al. BBMT 2020), occurring in 79.7% (102/128) of pts (Gr 4/5 14.0%; COVID-19 36.7% [Gr 5 6.3%]).Conclusion: Odronextamab demonstrated deep and durable responses in heavily pretreated pts with R/R FL; 91% of responders achieved CR, correlating with favorable PFS and OS at 24 mo. Odronextamab had a generally manageable safety profile and a low incidence of Gr 3 CRS/ICANS. Odronextamab could offer an important off-the-shelf Tx option for pts with heavily pretreated R/R FL. Citation Format: Geoffrey Chong, Michal Taszner, Silvana Novelli, Seok-Goo Cho, Jose C. Villasboas, Ana Jiménez Ubieto, Benoît Tessoulin, Michelle Poon, David Tucker, Jan Walewski, Yuqin Song, Emmanuel Bachy, Stephanie Guidez, Aranzazu Alonso, Deepa Jagadeesh, Stefano Luminari, Laura Magnano Mayer, Elżbieta Iskierka-Jażdżewska, Monica Tani, Jingxian Cai, Amulya Uppala, Saleem Shariff, Jurriaan Brouwer-Visser, Aafia Chaudhry, Hesham Mohamed, Srikanth Ambati, Tae Min Kim. Primary analysis of the Phase 2 ELM-2 study: Odronextamab in patients (pts) with relapsed/refractory follicular lymphoma (R/R FL) [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 CT243.

Abstract CT238: Associations of ctDNA levels during neoadjuvant treatment with pathological response in patients with resectable NSCLC from the phase 3 AEGEAN trial

Abstract Background: In AEGEAN, perioperative durvalumab (D) + neoadjuvant (neoadj) chemotherapy (CT) significantly improved pathological complete response (pCR) and event-free survival (primary endpoints), and major pathological response (MPR; key secondary endpoint), with manageable safety vs neoadj CT alone in patients with resectable NSCLC. We report exploratory ctDNA analyses during neoadj treatment (Tx) and associations of ctDNA dynamics and clearance with pathological response, including pCR, MPR and percentage residual viable tumor (%RVT). Methods: AEGEAN is a double-blind placebo (PBO)-controlled study (NCT03800134). Adults with Tx-naïve resectable NSCLC (stage II-IIIB[N2]; AJCC 8th ed) were randomized (1:1) to receive neoadj CT + D or PBO IV (Q3W, 4 cycles) prior to surgery (Sx), followed by D or PBO IV (Q4W, 12 cycles), respectively, after Sx. Evaluable resected samples from patients in the modified intent-to-treat (mITT) population (patients without known EGFR/ALK aberrations) were assessed centrally for %RVT and determination of pCR (absence of any RVT in resection specimen, including primary tumor and all sampled lymph nodes) and MPR (≤10% RVT in primary tumor) per IASLC recommendations. Plasma samples were collected prior to each neoadj Tx cycle (at baseline [BL], C2D1, C3D1, and C4D1) and before Sx. ctDNA analysis was performed using patient-specific, tumor-informed assays, following identification of mutations in Tx-naïve, diagnostic biopsies by whole exome sequencing. ctDNA variant allele fractions (VAFs; mutant sequences as a % of total sequence reads at ctDNA panel sites) and dynamics, including ctDNA clearance, were assessed during neoadj Tx, and their potential associations with pCR, MPR, or %RVT were evaluated. Results: ctDNA was evaluated in 831 samples from 186 patients (D arm, n=90; PBO arm, n=96) in the mITT population from the interim pCR analysis cohort (n=402). ctDNA dynamics were assessed during neoadj Tx in relation to whether patients had a pathological response at surgery; patients without surgery were designated as non-responders. BL VAF levels were not significantly different between patients who had tumors with vs without pCR (D arm, P=0.09; PBO arm, P=0.7) or MPR (D arm, P=0.4; PBO arm, P=0.8); however, on-Tx VAF levels were significantly lower in the D arm from C2D1 onwards in patients with vs without pCR (P≤0.001) or MPR (P≤0.01) and in the PBO arm from C3D1 for pCR (P≤0.003) or C2D1 for MPR (P≤0.002). %RVT was significantly lower in patients with vs without ctDNA clearance from C2D1 onwards in the D arm (median, <5% vs ≥30%, P≤0.01) and from C3D1 onwards in the PBO arm (median, 10% vs ≥50%, P≤0.0004). Conclusions: In AEGEAN, reduced VAF levels during neoadj Tx appeared associated with pCR or MPR. Patients in whom ctDNA clearance was observed tended to have a lower %RVT, from C2D1 in the D arm and from C3D1 in the PBO arm. Citation Format: Davina Gale, Zhou Zhu, Zhongwu Lai, Martin Reck, David Harpole, Janis M. Taube, Tetsuya Mitsudomi, Maximilian Hochmair, Thomas Winder, László Urbán, Jeronimo Rodriguez-Cid, Quincy Chu, Jamie Chaft, Ross Stewart, Darren Hodgson, Gary J. Doherty, John V. Heymach. Associations of ctDNA levels during neoadjuvant treatment with pathological response in patients with resectable NSCLC from the phase 3 AEGEAN trial [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 CT238.

Valemetostat for Relapsed or Refractory Peripheral T-Cell Lymphomas: Primary Results from a Phase 1 Trial

Introduction: Treatment (Tx) options for T-cell non-Hodgkin lymphomas (T-NHLs) are limited and prognosis is too often poor for patients (pts) with relapsed or refractory (R/R) disease. Enhancer of zeste homolog (EZH)2 and EZH1 are methyltransferases that catalyze trimethylation of histone H3 at lysine 27 (H3K27me3); this repressive transcriptional profile is broadly associated with gene silencing. Valemetostat tosylate (valemetostat) is a novel, potent, and selective dual inhibitor of EZH2 and EZH1 that prevents H3K27me3 and increases expression of genes involved in immune function ( SLA, PAG1) that can be silenced by H3K27me3. Valemetostat was approved in Japan for the Tx of R/R adult T-cell leukemia/lymphoma (ATLL) in 2022. The clinical activity of valemetostat in pts with R/R NHLs was investigated in the phase 1 DS3201-A-J101 (“J101”; NCT02732275) trial. Interim data were reported previously. Here we report primary outcomes for pts in J101 with R/R T-NHLs treated with valemetostat. Methods: This open-label, multicenter study was conducted in Japan and the United States (US). Eligible pts were ≥ 18 (US) or ≥ 20 (Japan) years (y) of age and relapsed from, refractory to, or ineligible for standard therapies. The trial included a dose-escalation phase (Japan only) followed by a dose-expansion phase (Japan & US). Enrollment in the expansion phase was limited to pts with R/R peripheral T-cell lymphoma (PTCL) or ATLL. Pts received valemetostat once daily in continuous 28-day (d) Tx cycles at 150-300 mg/d in the escalation phase and 200 mg/d in the expansion phase until disease progression or intolerance. Key endpoints for the dose-escalation and dose-expansion cohorts were safety and PK parameters. Preliminary efficacy assessment included objective response rate (ORR), complete response (CR) rate, duration of response (DOR), and progression-free survival (PFS). DOR and PFS were estimated using Kaplan-Meier methods. Results for PTCL and ATLL are reported separately. Results: At the primary data cutoff (Dec 31, 2022), 71 pts were included in the efficacy and safety analyses; 57 with PTCL and 14 with ATLL. Median age at baseline was 68.0 (range 26-83) y in the PTCL group and 66.5 (37-78) y in the ATLL group, and median prior therapies were 2.0 (1-8) and 2.5 (1-8), respectively; 16 (28%; 14 autologous, 2 allogeneic) pts with PTCL and 2 (14%, both allogeneic) with ATLL had previously undergone transplant. The most common PTCL subtypes were PTCL, not otherwise specified (PTCL, NOS; n = 26, 46%) and angioimmunoblastic T-cell lymphoma (AITL; n = 23, 40%). Tx was ongoing for 8 (11%) pts at data cutoff. All 71 pts included at data cutoff experienced ≥ 1 Tx-emergent adverse event; 59 (83%) pts had a Tx-related adverse event (TRAE). The most common all-grade TRAEs were cytopenias, dysgeusia, and alopecia; the most frequent grade ≥ 3 TRAEs were decreased neutrophil (17%), lymphocyte (11%), and platelet (14%) counts ( Table 1). TRAEs led to Tx discontinuation for 4 (6%) pts (1 each: acute myeloid leukemia, myelodysplastic syndrome, colitis, and acute kidney injury), dose reduction for 5 (7%) pts, and Tx interruption for 18 (25%) pts. The ORR was 55% (30/55) in the PTCL group and 64% (9/14) in the ATLL group, with CR rates of 31% (17/55) and 29% (4/14), respectively; within the PTCL group, the ORR among evaluable pts was 50% (13/26) for PTCL, NOS and 64% (14/22) for AITL ( Table 2). Median times to response were 1.8 (range 1.0-5.6) months (mo) in the PTCL group and 1.9 (1.7-19.4) mo in the ATLL group. Median DOR was 21.9 mo (95% confidence interval [CI], 10.2 mo to not reached [NR]) in the PTCL group (median follow-up 16.4 mo) and 21.2 (95% CI, 1.4 to 38.7) mo in the ATLL group (median follow-up 23.0 mo). Median PFS was 7.7 and 4.1 mo, respectively (median follow-up 18.2 mo and NR). Conclusions: Valemetostat was well tolerated and showed encouraging clinical activity in pts with R/R T-NHLs. Cytopenias were common but could usually be managed without Tx discontinuation. Valemetostat induced durable responses, with median DOR of > 1.5 y in both the PTCL and ATLL groups. Results for pts in this trial with R/R B-NHLs (Izutsu et al) and from a phase 2 trial in R/R T-NHLs (Horwitz et al) are reported separately.

A phase 2/3 trial of oral azacitidine (Oral-AZA) in patients (pts) with low- or intermediate-risk myelodysplastic syndromes (MDS).

TPS7083 Background: MDS, a heterogeneous group of clonal myeloid malignancies, are characterized by ineffective hematopoiesis and peripheral blood cytopenias, which can often lead to red blood cell (RBC) transfusion dependence and a risk of progression to acute myeloid leukemia (AML). In early clinical trials, 14- and 21-day (d) dosing regimens of the hypomethylating agent Oral-AZA were well tolerated and induced hematologic improvement (HI) in pts with lower-risk (LR) MDS. In a phase 3 trial, Oral-AZA 300 mg QD for 21d per 28d cycle significantly improved the rate of RBC transfusion independence (TI) and induced durable HI versus placebo (PBO) in patients (pts) with LR-MDS with RBC-transfusion-dependent anemia and thrombocytopenia (Garcia-Manero, et al. J Clin Oncol 2021). Grade 3/4 cytopenias were common in the Oral-AZA arm. Given the substantial clinical benefit of Oral-AZA observed in this setting, a new phase 2/3 trial is ongoing to further evaluate the 14d Oral-AZA regimen in pts with International Prognostic Scoring System Revised (IPSS-R)-defined low or intermediate (int)-risk MDS. Methods: This ongoing, multicenter, randomized, phase 2/3 trial (CA055-026; NCT05469737) will evaluate the safety and efficacy of Oral-AZA in pts with IPSS-R low- or int-risk MDS. Key eligibility criteria include ≥ 18 years, ECOG performance status score ≤ 2, and ≥ 1 cytopenia (anemia, thrombocytopenia, or neutropenia). Pts with an absolute neutrophil count < 0.5 × 109/L within a week of randomization will be excluded. Informed consent will be obtained from all participants. The phase 2 portion will enroll and randomize ~42 pts 1:1 to receive open-label Oral-AZA 200 or 300 mg QD for 14d per 28d cycle, plus best supportive care (BSC), to determine the recommended phase 3 dose (RP3D). The primary endpoints are safety and rate of complete remission (CR) within 6 Tx cycles. The secondary endpoints are overall response rate (ORR), and packed (p) RBC-TI and platelet-TI sustained for 84d in ≤ 6 Tx cycles. ORR includes CR, partial remission (PR), marrow CR, and any HI, per IWG 2006 response criteria. In the phase 3 portion, ~188 additional pts will be enrolled and randomized 1:1 to Oral-AZA at the RP3D or PBO for 14d per 28d cycle, plus BSC. Pts in the PBO arm with stable disease at Tx cycle 6 disease assessment or with documented disease progression after ≥ 3 Tx cycles will have the option to cross over into the Oral-AZA arm. The primary endpoint is CR in ≤ 6 Tx cycles. The key secondary endpoint is 84d pRBC-TI. Other secondary endpoints include those described in the phase 2 portion plus overall survival, event-free survival, time to AML progression, iron parameters, health-related quality of life, healthcare resource utilization, and safety parameters. Pts who benefit from Oral-AZA in phase 2 or 3 may continue to receive Tx in an extension phase. Trial recruitment began in December 2022 and is ongoing. Clinical trial information: NCT05469737 .

REAL‐WORLD DURATION OF VENETOCLAX TREATMENT FOR CHRONIC LYMPHOCYTIC LEUKEMIA AND SMALL LYMPHOCYTIC LYMPHOMA

Introduction: Venetoclax (V) is an approved fixed-duration treatment (tx) for chronic lymphocytic leukemia and small lymphocytic lymphoma (CLL/SLL), as a 12-cycle regimen (∼12 mos) with obinutuzumab (O) in the first-line (1L) setting or as a 24-cycle regimen (∼24 mos) with rituximab (R) in the relapsed/refractory (R/R) setting. We analyzed real-world tx patterns of V+O in 1L and V+R in R/R settings in patients (pts) with CLL/SLL in the United States. Methods: A retrospective cohort analysis was conducted using the IQVIA PharMetrics® Plus database to identify pts ≥18 y treated with V+O (1L cohort; May 2019 to September 2021) or V+R (R/R cohort; June 2018 to September 2021). Start of tx regimen was defined as the index date. All pts were required to have ≥1 diagnosis code for CLL/SLL and continuous enrollment 12 mos prior to and ≥3 mos after index date. Duration of tx (DoT) was defined as time from index date to earliest of either tx discontinuation (i.e., ≥60-d gap in V prescription refills) or censoring (i.e., end of follow-up). Fixed-duration tx cycle was defined as 12- or 24-cycle dosing (days 336−364 for 1L setting and days 707−735 for R/R setting, based on the dosing schedule plus 28 days). Kaplan-Meier analysis was used to estimate the probability of remaining on tx for the 1L and R/R cohorts. Results: A total of 116 pts in 1L setting (mean age, 62.3 y) and 145 pts in R/R setting (mean age, 64.2 y) were identified; 48.3% of R/R pts had prior targeted therapy. Median (95% CI) DoT in V+O pts (n = 115) was 12.4 (11.5, 13.4) mos over a median follow-up of 11.4 mos; probability of remaining on tx at 12, 18, and 24 mos was 56.4%, 20.2%, and 5.1%. Median (95% CI) DoT in V+R pts (n = 133) was 24.5 (13.4, 25.2) mos over a median follow-up of 15.5 mos; probability of remaining on tx at 24, 30, and 36 mos was 53.8%, 19.0%, and 19.0%. Among V+O pts, 47.8% (55/115) had ≥12 mos follow-up, of whom 9.1% had fixed cycles and 38.2% discontinued early (median DoT: 4.6 mos). Among V+R pts, 29.3% (39/133) had ≥24 mos follow-up, of whom 5.1% had fixed cycles and 46.2% discontinued early (median DoT: 7.1 mos). The remaining pts in each cohort had DoT >12 or 24 cycles (Table). Conclusions: While median DoT was approximately 12 mos for V+O-treated pts (1L setting) and 24 mos for V+R-treated pts (R/R setting), a high number of pts did not maintain the fixed-dosing schedule. This study provides evidence that a V-based approach may not be suitable for all pts with CLL/SLL. Encore Abstract—previously submitted to regional or national meetings (up to <1’000 attendees), EHA 2023 The research was funded by: AstraZeneca Keyword: Chronic Lymphocytic Leukemia (CLL) Conflicts of interests pertinent to the abstract A. Teschemaker Employment or leadership position: AstraZeneca Stock ownership: AstraZeneca S. Hakre Employment or leadership position: AstraZeneca Stock ownership: AstraZeneca J. Tse Research funding: AstraZeneca Pharmaceuticals. IQVIA received research funding from AstraZeneca to conduct this study. N. F. Shaikh Research funding: AstraZeneca Pharmaceuticals. IQVIA received research funding from AstraZeneca to conduct this study. Y. Gu Research funding: AstraZeneca Pharmaceuticals. IQVIA received research funding from AstraZeneca to conduct this study. A. Near Research funding: AstraZeneca Pharmaceuticals. IQVIA received research funding from AstraZeneca to conduct this study.

Real-World Treatment Experience of Venetoclax in Combination with Hypomethylating Agents in Patients with Newly Diagnosed Acute Myeloid Leukemia: Updated Experience from a Predominately Community Setting in the US

Introduction: Venetoclax (Ven) in combination with hypomethylating agents (HMAs) is approved to treat patients (pts) with newly diagnosed (ND) acute myeloid leukemia (AML) who are ineligible for intensive chemotherapy, based on the results from phase 1b (NCT02203773) and phase 3 (VIALE-A; NCT02993523) studies. This study aims to better understand pre- and post-VIALE-A real-world (rw) treatment (Tx) experience of Ven+HMA in routine clinical care. Methods: This retrospective cohort study used the Flatiron Health electronic health record-derived, nationwide, de-identified database. Pts with ND AML, aged ≥18 years, who initiated Ven+HMA Tx ≤1 month from AML diagnosis between June 1, 2018, and March 31, 2021 (excluding HMA Tx prior to AML diagnosis) were included. The study cohort was stratified into pre- (before July 1, 2020) vs post-VIALE-A (July 1, 2020 onwards). Timing of bone marrow (BM) biopsy, rw complete response/complete response with partial hematologic recovery (rwCR/CRh; <5% BM blasts with a platelet count >50×109/L and absolute neutrophil count [ANC] >0.5×109/L), and rwCR/complete response with incomplete hematologic recovery (rwCR/CRi; <5% BM blasts with either ANC <1000×109/L or platelet <100×109/L) were measured. Tx schedule modifications were documented. Kaplan-Meier analyses summarized time to last administration, time to first BM biopsy, time to first response (<5% BM blasts), time to death, or censoring at the end of follow-up on January 31, 2022. Cox regression analyses with a time varying covariate (Tx schedule modification) were conducted to examine the association between Ven Tx schedule modifications and overall survival (OS). Results: In total, 498 pts treated with Ven+HMA met the study criteria; most pts were treated in community practice (80%) vs academic settings (20%). Overall, 66% (330/498) of pts were pre-VIALE-A and 34% (168/498) were post-VIALE-A (median age was 76 and 75 years, secondary-AML was 33% and 27%, respectively). European LeukemiaNet 2017 classification: adverse, 42% vs 46%; intermediate, 22% vs 28%; favorable, 13% vs 9% for pre- vs post-VIALE-A cohorts, respectively. The median time from diagnosis to Ven Tx initiation was 12 days for the pre-VIALE-A cohort and 14 days for the post-VIALE-A cohort. Median time to last administration was 4.34 months for the pre-VIALE-A cohort (median follow-up: 8.98 months) and 4.67 months for the post-VIALE-A cohort (median follow-up: 8.52 months). Fewer pts in the post- vs pre-VIALE-A cohort (13% [22/168] vs 19% [63/330]) discontinued ≤60 days after Tx initiation (p=0.10). Overall, 65% (323/498) of pts with evaluable BM blast clearance were documented during follow-up and had low early mortality (death ≤60 days; <2% [<5/323]) vs 35% (175/498) of pts without an evaluable BM blast clearance who had higher early mortality (23% [40/175]). Amongst pts with BM blast clearance data available, more pts in the post- (61% [77/126]) vs pre-VIALE-A cohort (45% [101/225]) had their first biopsy by 28 ± 14 days after Tx initiation (proxy for Tx cycle 1). Earlier time to BM assessment after Ven Tx initiation in the post- vs pre-VIALE-A cohorts was associated with an earlier median time to first response (2.34 vs 5.14 months, respectively). More post- vs pre-VIALE-A pts with rwCR/CRi (n=45 vs n=93, respectively) had Ven schedule modifications after remission (days 0-30: 60% vs 39%; days 31-60: 36% vs 29%; anytime: 89% vs 74%). Most common reasons for Ven schedule modifications after remission, as documented in available physician notes (122 pre- vs 79 post-VIALE-A) were: toxic effect of Tx (88% vs 90%) and other reasons e.g. non-cancer related medical issues and cancer-related Tx (49% vs 51%; Table 1). Time-varying survival analysis showed that Ven Tx schedule modifications after remission were associated with longer median OS (Table 2). Conclusions: This study observed an evolution of earlier BM biopsy and an improvement in Ven Tx schedule modification in pts with ND AML who received Ven+HMA from pre- to post-VIALE-A, in a predominantly community setting in the US. Cytopenia was noted as a common reason for Ven Tx schedule modifications. Ven Tx schedule modifications after remission were associated with better median OS. Opportunities remain to further improve the number of pts with earlier BM assessment to determine Ven Tx schedule modifications and provide the best chance for optimal Tx outcomes for pts. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

1553O Health-related quality of life (HRQoL) in the phase III TROPiCS-02 trial of sacituzumab govitecan (SG) vs chemotherapy in HR+/HER2- metastatic breast cancer (MBC)

The antibody-drug conjugate SG comprises an anti-Trop-2 antibody coupled to SN-38 via a hydrolyzable linker. In the ongoing randomized TROPiCS-02 trial, SG is being evaluated vs single-agent chemotherapy treatment of physician’s choice (TPC) after CDK 4/6 inhibitor, endocrine therapy, and at least 2 chemotherapies in HR+/HER2- MBC setting. Here we assess the impact of SG on HRQoL in TROPiCS-02. Patients (pts) with locally determined HR+/HER2- MBC following (2-4 prior chemotherapies) for metastatic disease, were randomized to receive SG (10 mg/kg IV on days 1 and 8 of a 21-day treatment [Tx] cycle) or TPC (capecitabine, eribulin, gemcitabine, or vinorelbine). HRQoL was assessed at baseline (BL), day 1 of each Tx cycle (CxDx) and at end of treatment visit using the EORTC QLQ-C30. The analysis included all pts with valid HRQoL assessments at BL and ≥1 post-BL visit. Linear mixed-effect models for repeated measures were used to estimate differences in overall least-square mean changes from BL between Tx arms, using on-Tx data up to C11D1 (n ≥25 in both arms). The analysis included 446 pts (236 SG, 210 TPC; median age 56 y). The EORTC QLQ-C30 completion rate was ≥85% up to C13D1 in both Tx arms. Mean HRQoL scores at BL were generally similar for SG and TPC. The SG arm showed a trend of improvement in most HRQoL domains. A significantly greater improvement in physical functioning and dyspnea was observed for SG vs TPC and greater worsening in diarrhea (table).Table: 1553OEORTC QLQ-C30 least-square mean change from baselineSG vs TPC (95% CI)Global health status/QoL2.4 (-0.7, 5.5)FunctioningPhysical3.9 (0.9, 6.9)Role3.1 (-1.2, 7.4)Emotional0.9 (-2.4, 4.3)Cognitive-0.2 (-3.3, 2.9)Social0.8 (-3.2, 4.7)Summary Score0.6 (-1.8, 3.1)SymptomsFatigue-3.3 (-7.1, 0.5)Pain-1.6 (-5.5, 2.3)Nausea/Vomiting1.4 (-0.9, 3.8)Dyspnea-4.3 (-8.5, -0.1)Insomnia-3.7 (-8.1, 0.8)Appetite Loss-3.3 (-7.3, 0.8)Constipation-1.0 (-5.5, 3.4)Diarrhea10.4 (6.3, 14.5)Financial Difficulties0.9 (-2.5, 4.2)Positive value represents improvement for functioning and worsening for symptoms.SG, sacituzumab govitecan; TPC, treatment of physician’s choice. Open table in a new tab SG, sacituzumab govitecan; TPC, treatment of physician’s choice. Despite the association with worsening diarrhea, SG demonstrated an overall HRQoL benefit in heavily-pretreated patients with HR+/HER2- MBC.

P1041: IMPACT OF FEDRATINIB ON SPLEEN VOLUME AND MYELOFIBROSIS SYMPTOMS IN PATIENTS WITH SUBSTANTIAL SPLENOMEGALY: POST HOC ANALYSES FROM THE JAKARTA AND JAKARTA2 TRIALS

Background: In myelofibrosis (MF), splenomegaly is a marker of disease progression, and larger spleen size (SS) is correlated with poorer survival and debilitating symptoms. Fedratinib (FEDR) is an oral, selective Janus kinase 2 (JAK2) inhibitor approved as first-line (1L) treatment (Tx) of patients (pts) with MF and in pts previously treated with ruxolitinib (RUX). In the phase 3, placebo-controlled JAKARTA trial (NCT01437787) and the phase 2, single-arm JAKARTA2 trial (NCT01523171), pts experienced substantial improvements in spleen volume and MF symptoms after receiving 6 FEDR Tx cycles. Given the prognostic impact of splenomegaly, these analyses explore whether these clinical benefits were influenced by pre-Tx SS. Aims: Investigate the efficacy of FEDR 400 mg/d in JAKARTA and JAKARTA2, in pt subgroups defined by baseline (BL) SS. Methods: The JAKARTA trial assessed FEDR 400 mg/d, FEDR 500 mg/d, and placebo in pts with JAK inhibitor-naïve MF, and the JAKARTA2 trial evaluated FEDR 400 mg/d (starting dose) in pts resistant/intolerant to prior RUX. Both studies enrolled pts with intermediate- or high-risk MF, SS >5 cm from the left costal margin by palpation, platelets ≥50×109/L, and ECOG PS ≤2. These post hoc analyses included pts from both studies who were allocated to receive FEDR 400 mg/d (the approved dosage) in continuous 28-d Tx cycles. Pt subgroups were divided according to BL median SS (mSS) in each trial. Changes from BL in spleen volume and Myelofibrosis Symptom Assessment Form (MFSAF) total symptom score (TSS) were measured at the end of cycle 6 (EOC6). Spleen volume was assessed by MRI/CT scan; MFSAF TSS was the sum of 6 MF symptom scores: night sweats, early satiety, pruritus, pain under ribs-left side, abdominal discomfort, and bone/muscle pain. Eligible pts must have had spleen volume and/or TSS data at BL and EOC6. Results: Overall, 96 pts in JAKARTA and 97 pts in JAKARTA2 received FEDR 400 mg/d; mSS (range) at BL was 16 (5–40) cm and 18 (5–36) cm, respectively. In the JAKARTA <mSS and ≥mSS cohorts, median BL spleen volume was 1771 (316–3396) mL and 3329 (983–6430) mL, respectively, and median TSS was 13.0 (0.0–54.9) and 17.2 (0.4–57.0). In JAKARTA2, median BL spleen volume was 1937 (737–4305) mL and 4002 (1821–7815) mL for pts with <mSS and ≥mSS, respectively; BL TSS was 17.2 (0.7–48.0) and 23.6 (1.0–44.0). Overall, 75 (78%) pts in JAKARTA and 51 (53%) pts in JAKARTA2 had spleen volume data available at BL and EOC6; the <mSS and ≥mSS cohorts, comprised 37 and 38 pts, respectively, in JAKARTA, and 31 and 20 pts in JAKARTA2. Median spleen volume reduction (SVR) from BL was similar between the <mSS and ≥mSS cohorts in each trial, and 97% of pts with ≥mSS in both trials achieved some degree of SVR. In JAKARTA, median SVR at EOC6 was −38% (95% CI, −43 to −31) in the <mSS and −40% (95% CI, −40 to −28) in the ≥mSS cohort; in JAKARTA2, median SVR was −37 (95% CI, −43 to −30) in the <mSS and −38.5% (95% CI, −49 to −14) in the ≥mSS cohort. TSS data were available at BL and EOC6 for 71 (74%) pts in JAKARTA and 51 (53%) pts in JAKARTA2. Changes from BL in TSS at EOC6 were similar in the JAKARTA <mSS and ≥mSS cohorts, with median TSS reductions of −49% and −51%, respectively. Median TSS changes at EOC6 in JAKARTA2 were greater for pts with larger spleens, −36% and −49% in the <mSS and ≥mSS cohorts, respectively. Image:Summary/Conclusion: Pts who completed 6 Tx cycles with FEDR 400 mg/d, whether used as 1L MF Tx or after RUX Tx, experienced substantial improvements in spleen volume and MF symptom severity regardless of the extent of splenomegaly at BL.

P499: THE PHASE 1B OMNIVERSE TRIAL OF ORAL AZACITIDINE IN COMBINATION WITH VENETOCLAX FOR TREATMENT OF RELAPSED/REFRACTORY OR NEWLY DIAGNOSED ACUTE MYELOID LEUKEMIA (TRIAL IN PROGRESS)

Background: For older patients (pts) with acute myeloid leukemia (AML) who are ineligible for standard intensive chemotherapy (IC) regimens, traditional lower-intensity AML treatment (Tx) options include low-dose cytarabine (LDAC) or hypomethylating agents (HMAs; azacitidine [AZA] and decitabine), which are generally well tolerated but associated with suboptimal outcomes vs IC [Vey 2020]. Therefore, there remains a need for less toxic and more efficacious lower-intensity AML Tx regimens, especially agents that can be administered in the outpatient setting, which may increase convenience and reduce resource utilization. Venetoclax (VEN) is an oral, selective, small-molecule BCL2 inhibitor that has demonstrated considerable activity when combined with LDAC or HMAs in older pts with AML. In a recent phase 3 trial, VEN + injectable AZA significantly improved response and survival vs AZA alone in IC-ineligible pts with newly diagnosed (ND) AML [DiNardo 2020]. In the USA, VEN is approved in combination with an HMA or LDAC for Tx of pts with ND AML ≥ 75 years (y) of age or who cannot use IC due to comorbidities. Oral-AZA (CC-486) is approved for pts with AML in first remission (CR1) after IC who are ineligible for transplant or other curative therapies. In the randomized, phase 3 QUAZAR AML-001 trial of Oral-AZA in pts with AML in CR1 after IC, Oral-AZA 300 mg QD for 14 days (d)/28d Tx cycle was generally well tolerated and associated with significantly improved overall survival vs placebo. Gastrointestinal symptoms were the most common adverse events reported with Oral-AZA [Wei 2020]. Oral-AZA has also shown clinical activity in pts with active AML [Savona 2015]. As incorporation of AZA into DNA is S-phase-restricted, extended Oral-AZA dosing regimens (> 7d/28d Tx cycle) increase drug incorporation into cycling tumor cells to prolong epigenetic activity throughout the Tx cycle [Laille 2015]. An all-oral VEN + Oral-AZA combination regimen allows for outpatient administration and thus improves pt adherence [Eek 2016]. Aims: Describe the study design and objectives of the OMNIVERSE trial of Oral-AZA + VEN in older pts with ND AML or pts with AML relapsed/refractory (R/R) to prior Tx. Methods: OMNIVERSE (NCT04887857) is a multicenter, open-label, 2-part phase 1b trial (Figure). The key objectives of the trial are to assess safety and determine the maximum tolerated dose of Oral-AZA + VEN in pts with R/R AML (WHO 2016 criteria) ineligible to receive further IC (part I), and then in pts with ND AML ≥ 75 y of age, or those ≥ 18–74 y of age ineligible for IC or HSCT due to comorbidities (part 2). Main eligibility criteria include an ECOG performance status of 0–2 (ECOG 3 is allowed for pts ≥ 18–74 y of age with comorbidities) and an unfavorable cytogenetic risk profile for pts with ND AML. The initial dose of Oral-AZA is 300 mg QD × 14d/28d cycle, with de-escalation to 200 mg × 14d/28d cycle allowed for dose-limiting toxicities. VEN 400 mg is taken orally QD in continuous 28d cycles (or for 21d/cycle for dose level –2). A modified toxicity probability interval-2 design is used to evaluate the planned dose levels. The sample size is dependent on the dose levels included in the study (≤ 18 pts/part). Results: N/A Image:Summary/Conclusion: Study enrollment began in 2021. The trial is ongoing at clinical sites in the United States and Australia.

Updated results of the FOENIX-CCA2 trial: Efficacy and safety of futibatinib in intrahepatic cholangiocarcinoma (iCCA) harboring FGFR2 fusions/rearrangements.

4009 Background: Survival outcomes are historically poor in patients (pts) with advanced/metastatic iCCA, with median overall survival (mOS) times of approximately 1 year with first-line gemcitabine plus cisplatin and approximately 6 months with second-line chemotherapy. Futibatinib, a highly selective, irreversible FGFR1–4 inhibitor, demonstrated efficacy with durable responses in pts with iCCA harboring FGFR2 fusion/rearrangements in the pivotal FOENIX-CCA2 phase 2 study (NCT02052778). At the primary analysis of this trial (data cutoff: October 1, 2020), an objective response rate (ORR) of 41.7% was observed, with a median duration of response (mDOR) of 9.7 mo. Here, we report updated efficacy (including mature OS data) and safety data from the final analysis with an additional 8 mo of follow-up. Methods: FOENIX-CCA2 was a single-arm phase 2 study that enrolled pts with advanced/metastatic iCCA with FGFR2 fusion/rearrangement and progressive disease (PD) after ≥1 prior treatment (tx; including gemcitabine plus platinum-based chemotherapy). Pts received futibatinib 20 mg once daily until PD/intolerability. The primary endpoint was ORR per RECIST v1.1 by independent central review. Secondary endpoints were DOR, disease control rate (DCR), progression-free survival (PFS), OS, safety, and patient-reported outcomes. Results: At the time of the final data cutoff (May 29, 2021), median follow-up was 25.0 mo, and 96/103 pts (93%) had discontinued tx. The median number of tx cycles was 13.0 for a median tx duration of 9.1 mo. The confirmed ORR was 41.7% (43/103) and thereby the same as of the primary analysis, as was the DCR (at 82.5%). The ORR was consistent across pt subgroups. The mDOR was 9.5 mo, and 74% of responses lasted ≥6 mo. mPFS was 8.9 mo, with a 12-mo PFS rate of 35.4%. Mature mOS was 20.0 mo, with a 12-mo OS rate of 73.1% . No new safety signals were identified. Common tx-related adverse events (TRAEs) included hyperphosphatemia (85%), alopecia (33%), dry mouth (30%), diarrhea (28%), dry skin (27%), and fatigue (25%). TRAEs resulted in tx discontinuation in 4 pts (4%). No tx-related deaths occurred. Quality of life was maintained from baseline to tx cycle 13. Conclusions: Findings from the final analysis of FOENIX-CCA2 confirm the results of the primary analysis and reinforce the durable efficacy and continued tolerability of futibatinib in previously treated pts with advanced/metastatic iCCA harboring FGFR2 fusion/rearrangements. Mature OS data were consistent with data from the primary analysis and far exceed historical data in this patient population. Clinical trial information: NCT02052778.

Health-related quality of life (HRQoL) with enasidenib versus conventional care regimens in older patients with late-stage mutant-IDH2 relapsed or refractory acute myeloid leukemia (R/R AML).

7032 Background: Enasidenib (ENA) is an oral inhibitor of mutant-IDH2 (mIDH2) proteins. In the phase 3 IDHENTIFY trial, ENA improved event-free survival (EFS), overall response, and complete remission rate vs conventional care regimens (CCR) ( P &lt; 0.01 for all) in patients (pts) ≥ 60 years of age with m IDH2 R/R AML with 2 or 3 prior treatments (Tx) (DiNardo 2021). Pt-reported HRQoL was a secondary trial endpoint. Methods: IDHENTIFY is an open-label, randomized trial (NCT02577406). Pts were preselected to a CCR (SC azacitidine, intermediate- or low-dose Ara-C, or supportive care) and then randomized 1:1 to ENA 100 mg/d or CCR in 28-d cycles. Key HRQoL endpoints were mean changes from baseline (CFB) overall and by clinical response in the Global Health Status/QoL, Physical Functioning, Role Functioning, Fatigue, and Dyspnea domains of the EORTC QLQ-C30 questionnaire, and in EQ-5D-5L utility index (UI) and visual analogue scale scores. The QLQ-C30 and EQ-5D-5L were assessed on D1 of each Tx cycle (C) and at end of Tx. Minimally important differences (MIDs) in CFB scores within or between Tx arms were based on accepted thresholds. Sensitivity analysis using imputed data on CFB was conducted using pattern mixture modeling. Results: HRQoL-evaluable cohorts included 118/158 (74.7%) pts in the ENA arm and 80/161 (49.7%) in the CCR arm; 40 ENA pts and 81 CCR pts were not evaluable due to missing data at baseline (BL; 22 ENA and 51 CCR) and/or at ≥1 post-BL visit (26 ENA and 69 CCR). Pts ineligible for HRQoL analyses had lower response rates and worse EFS and overall survival than HRQoL-evaluable pts. Overall QLQ-C30 completion rates in the ENA and CCR arms were 79% and 65%, respectively ( P &lt; 0.001). While there was no meaningful improvement or worsening from BL (ie, exceeding MID) within either Tx arm in the key QLQ-C30 domains, scores worsened during initial Tx cycles and then improved with continued Tx. Mean EQ-5D-5L scores also worsened during early cycles in both Tx arms, with meaningful UI deterioration in the ENA arm from C2 through C7. However, between-group comparisons showed no consistent differences between ENA and CCR in mean CFB. Sensitivity analysis with imputation of missing CFB data showed worsened HRQoL compared with non-imputed data in the CCR arm but not with ENA. In the ENA arm, clinical responders reported relatively stable mean HRQoL scores over time, and non-responders showed no meaningful differences in CFB vs the CCR arm. Conclusions: HRQoL measures tended to worsen during early cycles in both Tx arms and gradually improved with continued Tx. Data should be interpreted with caution as only approximately one-half of pts in the CCR arm were HRQoL-evaluable. ENA improved clinical efficacy measures vs CCR without compromising HRQoL in older pts with R/R AML. Clinical trial information: NCT02577406.

Oral azacitidine plus venetoclax in patients with relapsed/refractory or newly diagnosed acute myeloid leukemia: The phase 1b OMNIVERSE trial.

TPS7068 Background: For patients (pts) with acute myeloid leukemia (AML) who cannot undergo intensive chemotherapy (IC), lower-intensity treatment (Tx) regimens, including low-dose cytarabine (LDAC) and hypomethylating agents (HMAs; azacitidine [AZA], decitabine), are generally well tolerated but are associated with lower response rates than IC [Vey 2020]. Similarly, the BCL2 inhibitor, venetoclax (VEN), has shown antileukemic activity, although only modest clinical benefit as monotherapy [Konopleva 2016]. VEN + AZA shows synergistic activity in preclinical models, enhancing leukemic cell apoptosis in vitro and anti-tumor activity in vivo [Jin 2020]. In IC-ineligible pts with ND AML, VEN + injectable AZA significantly increased complete remission (CR)/CR with incomplete hematologic recovery (CRi) rates ( P &lt; 0.001) and prolonged overall survival (OS; P &lt; 0.001) vs AZA only [DiNardo 2020]. VEN, in combination with an HMA or LDAC, is approved in the US for Tx of pts with ND AML ≥ 75 years (y) of age or who cannot undergo IC due to comorbidities. Oral-AZA (CC-486) is approved for Tx of pts with newly diagnosed (ND) AML in first CR or CRi after IC who cannot receive curative therapy (eg, HSCT). In the phase 3 QUAZAR AML-001 trial, maintenance Tx with Oral-AZA 300 mg QD for 14 days (d)/28-d Tx cycle improved OS and relapse-free survival vs placebo in older pts in CR/CRi after IC [Wei 2020]. Incorporation of AZA into DNA is S-phase-restricted; thus, extending AZA exposure over a longer duration by using an oral formulation increases the opportunity for cycling tumor cells to incorporate the drug to sustain therapeutic activity [Laille 2015]. Additionally, an all-oral combination regimen allows for outpatient administration to optimize pt convenience and reduce resource utilization. Methods: OMNIVERSE (NCT04887857) is an open-label, multicenter, 2-part phase 1b trial. The main goals are to evaluate safety and establish the maximum tolerated dose of Oral-AZA + VEN in pts ≥ 18 y of age with relapsed/refractory AML who are ineligible for further IC ( part 1), and subsequently, in pts with ND AML ≥ 75 y of age, or pts 18–74 y of age with comorbidities that prevent use of IC or HSCT ( part 2). Key eligibility criteria include ECOG performance status of 0–2 (ECOG 3 is allowed for pts 18–74 y of age with comorbidities) and unfavorable-risk cytogenetics for pts with ND AML. The Oral-AZA starting dose is 300 mg QD × 14 d/28-d cycle, which can be de-escalated to 200 mg QD × 14 d depending on dose-limiting toxicities; oral VEN 400 mg QD is taken continuously (or 21 d/cycle for dose level −2). A modified toxicity probability interval-2 design is used to evaluate dose levels. Sample size depends on the dose levels utilized (≤ 18 pts/part). Enrollment began in 2021. The trial is ongoing at clinical sites in the United States and Australia. Clinical trial information: NCT04887857.

Trial in progress update on ENGOT-cx8/GOG-3024/innovaTV 205: Addition of a new cohort with first-line (1L) tisotumab vedotin (TV) + pembrolizumab (pembro) + carboplatin (carbo) ± bevacizumab (bev) in recurrent/metastatic cervical cancer (r/mCC).

TPS5603 Background: Despite the use of platinum-taxane doublets ± bev in eligible patients (pts), overall survival (OS) outcomes for pts with r/mCC remain poor. With the US approval of pembro + chemotherapy ± bev in the 1L setting for r/mCC with ≥1% of programmed death ligand 1–positive cells in the tumor, an unmet need remains for pts who do not meet this threshold and for pts who progress or are intolerant to standard treatment (tx). TV is a tissue factor–directed antibody–drug conjugate that has been granted accelerated approval in the United States for the tx of adults with r/mCC with disease progression on or after chemotherapy. To develop more effective treatments, we investigated TV in combination with agents with known activity in cervical cancer. We conducted a 2-part, multicohort phase 1b/2 trial, ENGOT-cx8/GOG-3024/innovaTV 205 (NCT03786081), to evaluate TV in combination with bev, pembro, or carbo. The phase 1b dose-escalation phase of innovaTV 205 established the recommended phase 2 dose (RP2D) and the feasibility of these doublet combinations (Monk et al, IGCS 2021). Moreover, we recently reported encouraging antitumor activity from the dose-expansion cohort of TV + carbo (1L; confirmed objective response rate [ORR], 55%; median duration of response [DOR], 8.3 mo) and TV + pembro (second-line; confirmed ORR, 38%; median DOR, 13.8 mo) (Vergote et al, ESMO 2021). The current report describes the design of a new, ongoing dose expansion cohort in the innovaTV 205 study to evaluate the combinations of TV, pembro, and carbo ± bev. Methods: A new cohort has been added to the innovaTV 205 study, comprising adult pts with recurrent or stage IVB squamous, adenosquamous, or adenocarcinoma of the cervix with no prior systemic therapy and an Eastern Cooperative Oncology Group score of 0 or 1. Pts will be treated with the RP2D of TV (2.0 mg/kg) + carbo (AUC 5 mg/mL), pembro (200 mg), and bev (15 mg/kg) every 3 weeks or with TV + carbo (AUC 5 mg/mL) and pembro (200 mg). To assess the regimen’s initial tolerability, there will be a dose-limiting toxicity evaluation period that will consist of completion of 1 tx cycle of 21 days for 6 pts enrolled to receive the quadruplet combination. The primary endpoint of this dose expansion phase is confirmed ORR per RECIST v1.1; secondary endpoints include DOR, time to response, progression-free survival, OS, and safety. Enrollment is ongoing in the United States and Europe, with additional sites planned globally. Clinical trial information: NCT03786081.

Health-related quality of life (HRQoL) in patients with relapsed/refractory multiple myeloma (RRMM) receiving real-life current standard of care (SOC) in the LocoMMotion study.

8030 Background: Evaluation of patient (pt)-reported outcomes provides insight into how real-life SOC treatments (tx) affect HRQoL for pts with RRMM. LocoMMotion (NCT04035226) is the first prospective, multinational study of real-life SOC in triple-class exposed pts with RRMM. Here, we present measures of symptoms, functioning, and overall HRQoL. Methods: LocoMMotion is a prospective, noninterventional study across 76 sites (63 European; 13 US). Pts had received ≥3 prior lines of therapy (LOT) or were refractory to PI and IMiD; received PI, IMiD, and anti-CD38 mAb; and had disease progression during/after last LOT. Real-life SOC tx were defined as those used in local clinical practice. The questionnaires were EORTC QLQ-C30, 4 single items from EORTC QLQ-MY20, and EQ 5D-5L. HRQoL was assessed at baseline (BL), day 1 of each tx cycle, end of tx visit, and during the follow-up period (every 4 weeks). Improvement compared to BL health status was evaluated using established thresholds. Within-group change was assessed using mixed models for repeated measures. Results: Questionnaire completion for pts in the LocoMMotion study (N=248; 54.4% male; median age 68 yrs; median 4.0 [range, 1–20] cycles of SOC) was 75.6% during SOC tx. Most pts did not achieve meaningful improvement in PRO scores, defined by a literature-based minimally important difference of 10 points in mean score. This was most pronounced in pain symptoms (62% of pts had no meaningful improvement during the first 3 months of tx; 55% had no improvement during full tx duration). For the overall population, the least square (LS) mean changes from BL during SOC tx and subsequent LOT are described (Table). Pts who achieved very good partial response and better during SOC tx had greater improvement in PRO scores, including in LS mean change for pain score (-14.9 [95% confidence interval (CI): -22.9, -7.0]). Conclusions: In this first prospective study of real-life current SOC in triple-class exposed pts, limited gains in HRQoL were reported, most notably in pain symptoms. There is an urgent need for effective therapies that can help pts achieve deep responses and delay disease progression, as these are associated with improved HRQoL. Clinical trial information: NCT04035226. [Table: see text]

Health-Related Quality of Life (HRQoL) during Treatment with Enasidenib (ENA) Plus Azacitidine (AZA) in Patients with Newly Diagnosed Mutant IDH2 (m IDH2) Acute Myeloid Leukemia (AML) Not Eligible for Intensive Chemotherapy (IC)

Health-Related Quality of Life (HRQoL) during Treatment with Enasidenib (ENA) Plus Azacitidine (AZA) in Patients with Newly Diagnosed Mutant IDH2 (m IDH2) Acute Myeloid Leukemia (AML) Not Eligible for Intensive Chemotherapy (IC)

Safety and Tolerability of Fedratinib (FEDR), an Oral Inhibitor of Janus Kinase 2 (JAK2), in Patients with Intermediate- or High-Risk Myelofibrosis (MF) Previously Treated with Ruxolitinib (RUX): Results from the Phase 3b FREEDOM Trial

Safety and Tolerability of Fedratinib (FEDR), an Oral Inhibitor of Janus Kinase 2 (JAK2), in Patients with Intermediate- or High-Risk Myelofibrosis (MF) Previously Treated with Ruxolitinib (RUX): Results from the Phase 3b FREEDOM Trial

Long-Term Overall Survival (OS) with Oral Azacitidine (Oral-AZA) in Patients with Acute Myeloid Leukemia (AML) in First Remission after Intensive Chemotherapy (IC): Updated Results from the Phase 3 QUAZAR AML-001 Trial

Long-Term Overall Survival (OS) with Oral Azacitidine (Oral-AZA) in Patients with Acute Myeloid Leukemia (AML) in First Remission after Intensive Chemotherapy (IC): Updated Results from the Phase 3 QUAZAR AML-001 Trial

OMNIVERSE: A Phase 1b/2 Study of Oral Azacitidine Plus Venetoclax in Patients with Relapsed/Refractory (R/R) or Newly Diagnosed (ND) Acute Myeloid Leukemia (AML)

OMNIVERSE: A Phase 1b/2 Study of Oral Azacitidine Plus Venetoclax in Patients with Relapsed/Refractory (R/R) or Newly Diagnosed (ND) Acute Myeloid Leukemia (AML)

Real World Treatment Patterns and Outcomes of Venetoclax (Ven) and Hypomethylating Agents (HMA) in Patients with Newly Diagnosed Acute Myeloid Leukemia (AML) in the United States

Real World Treatment Patterns and Outcomes of Venetoclax (Ven) and Hypomethylating Agents (HMA) in Patients with Newly Diagnosed Acute Myeloid Leukemia (AML) in the United States