Cherian, Mathew

PURPOSEThere are numerous barriers to enrollment in oncology biomarker-driven studies.METHODSThe ELAINE 2 study (ClinicalTrials.gov identifier: NCT04432454 ) is an open-label phase 2 study of lasofoxifene combined with abemaciclib in patients with advanced or metastatic estrogen receptor–positive/human epidermal growth factor receptor 2–negative breast cancer with an ESR1 mutation. ELAINE 2 opened clinical sites by using a Traditional approach, which activated a site before patient identification, and the Tempus TIME Trial network, which opened a site only after identifying an eligible patient. This manuscript presents the operational metrics comparing the Traditional and TIME Trial site data.RESULTSThe study enrolled patients over 34 weeks and 16 sites (six Traditional and 10 TIME Trial) participated. Duration for full clinical trial agreement execution for Traditional sites and TIME Trial sites averaged 200.5 (range, 142-257) and 7.6 days (range, 2-14), respectively. Institutional review board approval time for Traditional sites and TIME Trial sites was 27.5 (range, 12-71) and 3.0 days (range, 1-12), respectively. Duration from study activation to first consent was 33.3 (range, 18-58) and 8.8 days (range, 1-35) for Traditional and TIME Trial sites, respectively. The first patient on study was at a TIME Trial site 115 days before a Traditional site and the first seven patients enrolled were at TIME Trial sites. Traditional sites consented 23 and enrolled 16 patients, while TIME Trial sites consented 16 and enrolled 13. The trial enrolled 29 patients in 8.5 months with the anticipated enrollment duration being 12-18 months.CONCLUSIONThe TIME Trial network opened earlier and enrolled the first study patients. These results demonstrate that the Just-in-TIME model, along with a Traditional model, can improve enrollment in biomarker-driven studies.

1057 Background: Endocrine therapy (ET), particularly aromatase inhibitors (AIs), for estrogen receptor (ER)-positive breast cancer can lead to acquired ESR1 mutations ( mESR1) driving endocrine resistance and tumor progression. Treatments for mBC with mESR1 are limited, especially after progression on ET/cyclin-dependent kinase 4 and 6 inhibitor (CDK4/6i) combinations. In ELAINE 2, LAS, a next-generation ET (breast ER antagonist) plus Abema had a median progression-free survival (PFS) of ~13 mos, objective response rate (ORR) of 33%, and 24-wk clinical benefit rate (CBR) of 62% with a favorable safety profile in patients with resistant mESR1 mBC (Damodaran S, et al. J Clin Oncol. 2022;40:16 suppl 1022). Here, we report ELAINE 2 data with longer patient follow up (Jan 31, 2023). Methods: In this open-label, phase 2, single-arm study, 29 women with mESR1, ER+/HER2- mBC that progressed on prior ET took oral LAS 5 mg/day and Abema 150 mg BID until disease progression/toxicity. The primary endpoint was safety/tolerability; secondary included PFS, CBR, and ORR. Data were summarized descriptively with no formal hypothesis testing. Results: Patients (median age 60 yrs) had received a median of 2 prior therapy lines for mBC; all but one had prior CDK4/6i exposure and 14 (48%) had prior chemotherapy for mBC. LAS/Abema was well tolerated with primarily grade 1/2 treatment-emergent adverse events (most commonly diarrhea, nausea, fatigue, and vomiting). One treatment withdrawal occurred due to grade 2 diarrhea. No deaths occurred. LAS dose was not reduced; Abema dose was reduced to 100 mg BID in 6 (21%) patients. Median PFS was 56.0 wks (~13 mos) and CBR 65.5% (95% CI, 47.3‒80.1). Median overall survival was not estimable. In 18 patients with measurable lesions, ORR was 55.6% (95% CI, 33.7‒75.4), with median time to response of 5.7 mos and median duration of response of 6.4 mos. Seventy-six percent, 56%, and 39% of patients were progression free at 6, 12, and 18 mos, respectively. Three (10%) patients had scan-identified venous thromboembolic events, with one symptomatic pulmonary embolism and one symptomatic deep vein thrombosis. In 26 patients with evaluable baseline and wk 4 ctDNA, ESR1 mutant allele fraction decreased from baseline to wk 4 in 81% of patients and was not detected in 54%. Conclusions: With longer ELAINE 2 follow up, LAS/Abema continues to be well tolerated with clinically meaningful efficacy in women with mESR1, ER+/HER2- mBC that had progressed on ET and CDK4/6is. Decreases in mESR1 ctDNA suggest effective target engagement of LAS. The PFS (median ~13 mos) and ORR (56%) with LAS/Abema are promising and a confirmatory phase 3 study (ELAINE 3) will begin in 2023. If ELAINE 2 results are confirmed, the combination of LAS and Abema would address a critical unmet need, providing a practice changing option for treating mESR1 breast cancer. Clinical trial information: NCT04432454 .

1504 Background: Trial recruitment that requires specific actionable mutations based on next-generation sequencing (NGS) is challenging. Barriers can include competing studies, physician study awareness, site proximity, mutation incidence, among other concerns. Methods: This study (NCT04432454) opened clinical sites using two methods during the COVID-19 pandemic. The “Traditional” approach included site selection, IRB and contract approval, and trial activation prior to a patient being identified for enrollment. The second approach used the Tempus “TIME” Trials network that would only open a site after identifying a patient with a mutation of interest and eligible for the trial. Results: The first patient enrolled was on 10/12/20 and the last patient was on 6/24/21. A total of 16 sites (6 Traditional and 10 TIME) participated. All Traditional sites, and none of the TIME sites, were affiliated with major academic institutions. Duration for full CTA execution for Traditional sites averaged 200.5 days (range 142 to 257) and for TIME sites averaged 7.6 days (range 2 to 14). IRB approval time average for Traditional sites was 27.5 days (range 12 to 71) and TIME sites was 3.0 days (range 1 to 12 days). Days from site selection to activation letter for Traditional sites was on average 250.0 days (range 187 to 281) and for TIME sites was 131.6 days (range 22 to 248). Time from study activation to first consent was 33.3 days (range 18 to 58) for Traditional sites and 8.8 days (range 1 to 35) for TIME sites. The first patient on-study was at a TIME site 115 days prior to a Traditional site and the first 7 patients enrolled were at TIME sites. Traditional sites consented 23 and enrolled 16 patients while the TIME sites consented 16 and enrolled 13. The trial enrolled all 29 patients in 8 months with the anticipated enrollment duration being 12 to 18 months. Conclusions: Although the Traditional and TIME programs had different operational models, they both contributed a significant number of patients and reduced the projected enrollment timeline. TIME sites enrolled the initial patients. These results demonstrate that the “Just-in-Time model,” in conjunction with a Traditional model, can reduce projected overall time to enrollment in biomarker-driven studies. [Table: see text]

e18739 Background: Hair loss is a well-known side effect of chemotherapy. The Paxman Hair Loss Prevention System, a scalp cooling device, has been shown to be effective in reducing chemotherapy induced alopecia in patients receiving chemotherapy (Nangia, JAMA, 2017). The National Comprehensive Cancer Network and the European Society for Medical Oncology guidelines have recommended scalp cooling as category 2A and 2B options, respectively. Methods: The real world use of scalp cooling using the Paxman device, as documented by orders through the Paxman Hub during the years of 2017-2020 was summarized. Descriptive statistics were used to summarize demographics and utilization. Results: Data from 6649 patients who used scalp cooling were reviewed. Patients with breast cancer were the most common users of scalp cooling (78%, n=5197) followed by gynecology (12%, n=775), gastrointestinal (3%, n=201), lung (1%, n=81) and genitourinary (1%, n=52). The majority of patients were between the ages of 45-65 (55%), followed by 65-74 (18%), older than 75 (5%), and 25-44 (2%). Average number (#) of cycles of cooling completed was 6.53 (range of average # of cycles 4.50-12). Scalp cooling with this device was commonly used in 39 out of 50 states. Conclusions: This is the largest report of scalp cooling usage in the real world setting in the USA, including scalp cooling usage in older adults. Uptake of scalp cooling across various cancers has not been uniform and this deserves further study.

Abstract BACKGROUND: Azacitidine and decitabine are indicated for the first line treatment of intermediate and high risk MDS. About 40% to 47% of patients respond to 1st line hypomethylating agents. The median duration of response is 13 months. There are no effective therapies for patients who fail to respond to or progress on hypomethylating agents. A phase II trial of high dose lenalidomide (50mg/day) induction therapy followed by low dose (10mg/day) maintenance therapy in elderly patients with AML had demonstrated a high CR/CRi of 30%. CR was restricted to patients with presenting WBC counts <10000/µL, peripheral blast counts <1000/ µL and < 30%, many of whom could have been classified as having MDS rather than AML by FAB criteria. With the rationale that MDS and AML represent a continuum of disease, and the promising results in AML we aimed to assess the clinical activity of high dose lenalidomide by conducting a clinical trial of high dose Lenalidomide induction followed by low dose maintenance in patients with hypomethylating agent refractory MDS. METHODS: We conducted an open label, single arm, multi-center phase II trial of high dose lenalidomide induction (50mg/day for two 28 day cycles) followed by low dose lenalidomide maintenance therapy (10mg/day for 12 cycles) for patients with MDS (as defined by FAB criteria) refractory to hypomethylating agents. Patients who had failed to show CR, PR or HI (hematological improvement) after at least 6 cycles of azacytidine or decitabine or who had progressed on treatment were considered eligible. Patients were enrolled in a Simon's optimal two-stage design with an intended sample size of 43. The primary endpoint was proportion of confirmed responses (CR, PR or HI), as defined by international working group criteria, during the 14 cycles of treatment. RESULTS: 24 patients were enrolled in the first stage of the study. 16 patients completed at least one cycle of therapy and were considered evaluable for efficacy. Efficacy: Characteristics and outcomes of patients are detailed in Table 1. There were no complete or partial remissions. Marrow complete remission (MCR) was seen in 8/16 patients (50%). One of the 8 patients with a MCR had 5q- karyotype; 3/8 had trisomy 8 and one patient had a complex karyotype with monosomy 7. Median duration of MCR was 70 days (range 28-336 days). MCR lasted beyond the high dose induction period in 2 patients, one of whom had a 5q interstitial deletion (112 days) and one patient with trisomy 8 (336 days). Hematologic improvement (HI) was seen in 2/16 patients (12.5%) (Refer to table below). Toxicity: ≥grade 3 toxicities included pneumonia (12/24, 50%), sepsis (4/24, 17%), febrile neutropenia (8/24, 33%), rash (2/24, 8%), thromboembolic event (1/24), MI (1/24), new cancer -mammary analogue salivary carcinoma- (1/24). TABLE 1 Pt No: Age IPSS Prior cycles of 5-aza/ decitabine Cycles of Lenalidomide Reason off trial Best Response 1 69 1.5 2 4 Pancytopenia MCR 2 78 3 8 1 Death-Unrelated SD 3 73 2 7 1 Consent withdrawn SD 4 87 2 14 12 Progression MCR, HI-p&n 6 72 2 13 2 Thrombocytopenia MCR 7 69 2 13 1 PE SD 8 75 1 7 2 New Cancer MCR 9 74 1 4 3 Progression SD 10 75 2 0 2 Progression SD 11 72 1 13 3 Thrombocytopenia MCR 12 75 3 6 1 Progression PD 13 78 1 9 3 Gr3 Fatigue MCR 14 70 0 19 2 Progression MCR, HI-p 15 72 1 23 1 Progression PD 16 73 1 8 2 Gr 3 fatigue MCR CONCLUSIONS: High dose lenalidomide followed by standard dose maintenance in hypomethylating agent refractory MDS resulted in a marrow complete remission rate of 50% and hematological improvement rate of 12.5%. Future protocols should explore whether an extended schedule of intermittent dosing of high dose lenalidomide would allow for improved efficacy with acceptable toxicity. Disclosures Off Label Use: Lenalidomide is used in this study in patients with MDS both with and without deletion 5q.Use in patients without deletion 5q is off label use.. Tibes:Tetralogic Pharmaceuticals: Research Funding. Stockerl-Goldstein:Celgene: Speakers Bureau. Jacoby:Norvo Nordisk: Consultancy. Cashen:Celgene: Speakers Bureau. Vij:Onyx: Honoraria, Research Funding; Sanofi: Honoraria; Jannsen: Honoraria; Novartis: Honoraria; Millennium: Honoraria; Celgene: Honoraria, Research Funding.