Investigator-assessed Clinical Response Research Articles

Phase 1 Study of CART-Ddbcma for the Treatment of Patients with Relapsed and/or Refractory Multiple Myeloma: Results from at Least 1-Year Follow-up in All Patients

Introduction: CART-ddBCMA, an autologous anti-B-cell maturation antigen (BCMA) chimeric antigen receptor (CAR) T-cell therapy with a unique, synthetic binding domain, is being studied in a first-in-human clinical trial in patients (pts.) with relapsed &/or refractory multiple myeloma (RRMM). One-year or more follow-up clinical data from all patients are presented in this report. Methods: Details of study design have been previously reported (Frigault et al Blood Adv 2023). Briefly, pts with RRMM who have received ≥3 prior lines of therapy were enrolled & received a single infusion of CART-ddBCMA following lymphodepletion chemotherapy (fludarabine: 30 mg/m 2/d & cyclophosphamide: 300 mg/m 2/d daily for 3 days). Two dose levels (DL1 & DL2 respectively) of 100 & 300 (±20%) ×10 6 CAR+ cells were evaluated. The primary endpoints included incidence of adverse events (AEs) & dose-limiting toxicities (DLTs). Additional endpoints included quality & duration of clinical response assessed according to the IMWG Uniform Response Criteria for MM, evaluation of minimal residual disease (MRD), progression-free (PFS) & overall survival (OS). Correlative analyses related to CART-ddBCMA expansion, characterization, patient & disease-related features were also evaluated. Results: As of June 2, 2023, 40 pts; median age 66 years (range: 44-76) were enrolled; 38 received CART-ddBCMA (32, DL1; 6, DL2) & 38 were evaluable for initial safety & clinical response. Two pts who were not dosed had cell product manufactured but were not eligible for cell infusion due to medical complications. Pts had a median of 4 (range: 3-16) prior lines of therapy. All infused pts (100%) were triple-refractory, & 26 (68%) were penta-refractory; 34 pts (89%) were refractory to last-line of treatment; 9 pts (24%) had high tumor burden with ≥60% bone marrow plasma cells; 13 (34%) pts had extramedullary disease; & 11 (29%) pts had high-risk cytogenetics (Del 17p, t(14;16), t(4;14)) at baseline. Median follow-up after CART-ddBCMA infusion was 22 months (range: 9-40 months). CAR+ cells comprised a median 70% (range: 48-87%) of total CD3+ T cells; median vector copy number was 2.2 copies/cell (range: 1.1-3.5); median cell viability was 98% (range: 90-100%), & median cell manufacturing yield was 1174 ×10 6 CAR + cells (range: 470-1626 ×10 6). CART-ddBCMA product characteristics were consistent with the specifications in all the lots, & there were no manufacturing failures. CRS occurred in 36/38 (95%) pts but only 1 pt in DL2 had grade (Gr) 3 CRS & all other cases were Gr≤2. ICANS occurred in 7 pts (5, Gr≤2; 2, Gr3), with 1 Gr3 case in each DL. All cases of CRS & ICANS resolved without further sequalae with management. No cases of off-tumor cell mediated toxicity, delayed neurotoxicity events (i.e., occurring after day 28), or Parkinsonian-like symptoms were observed. All 38 evaluable pts demonstrated investigator-assessed clinical response per 2016 IMWG criteria (ORR, 100%) with 22 sCR, 7 CR (≥CR rate, 76%), 6 VGPR (≥VGPR rate, 92%), & 3 PR. Responses deepened over time & conversion to CR/sCR was observed with longer follow-up (as late as month 12). Of those evaluable for MRD testing to date (n=29), 25 (86%) were MRD-neg at 10 -5. Median duration of response, PFS, & OS were not reached at the time of data-cut because 25 of 38 evaluable pts (66%) had ongoing response. The Kaplan-Meier estimated PFS rates for 6, 12 & 18 months were 92%, 74%, & 67% respectively. Durable responses were also observed in patients with high-risk features (EMD, BMPC ≥ 60%, or B2M ≥ 5.5 at baseline) & high-risk cytogenetics. PFS rates at 6-, 12-, & 18-months are shown in Table 1. Based on the results from the study, a dose of 115 ± 10 ×10 6 cells, consistent with DL1, was recommended for the phase 2 study. Conclusions: Adverse events with CART-ddBCMA, including CRS & ICANS, were manageable & no off-tumor tissue-targeted toxicity, delayed neurotoxicity, or Parkinsonian-like events were observed in the entire cohort at the time of data-cut. Ongoing efficacy results are encouraging, with 100% ORR, including 35 (92%) response of VGPR or better & 29 (76%) with CR/sCR. More importantly, clinical responses were durable with an overall estimated 18-mo PFS rate of 67% with comparable clinical responses seen in ‘high-risk’ patients known to have poor prognosis. Updated data with additional follow-up based on later data-cut will be presented.

Real-world evidence of osimertinib in Chinese patients with EGFR T790M-positive non-small cell lung cancer: a subgroup analysis from ASTRIS study

PurposeASTRIS study aimed the largest to evaluate the effectiveness and safety of second- or higher-line osimertinib in patients with advanced/metastatic epidermal growth factor receptor (EGFR) T790M mutation-positive non–small cell lung cancer (NSCLC) in the real-world setting. Here we report the results of Chinese patients in ASTRIS study.MethodsAdults with EGFR T790M-positive advanced NSCLC pretreated with EGFR-tyrosine kinase inhibitor (EGFR-TKI), having a WHO performance status score of 0–2 and asymptomatic, stable central nervous system (CNS) metastases were included. All patients received once-daily osimertinib 80 mg orally. The outcomes included investigator-assessed clinical response, progression-free survival (PFS), time-to-treatment discontinuation (TTD), and safety.ResultsA total of 1350 patients were included. Response rate was 55.7% (95% confidence interval [CI] 0.53–0.58). The median PFS and the median TTD were 11.7 months (95% CI 11.1–12.5) and 13.9 months (95% CI 13.1–15.2), respectively. Overall, 389 patients (28.8%) had at least one protocol-specified adverse event (AE); AEs of interstitial lung diseases/pneumonitis-like events and QT prolongation were reported in 3 (0.2%) and 59 (4.4%) patients, respectively.ConclusionOsimertinib was effective in Chinese patients with T790M-positive NSCLC who had progressed after first- or second-generation EGFR-TKI in real-word setting and the results were consistent with ASTRIS study overall population and AURA studies. No new safety signals or events were identified.Clinical trial numberNCT02474355.

Efficacy and safety of tedizolid for the treatment of ventilated gram-positive hospital-acquired or ventilator-associated bacterial pneumonia in Japanese patients: Results from a subgroup analysis of a phase 3, randomized, double-blind study comparing tedizolid and linezolid

IntroductionThe results from the phase 3 study that evaluated the efficacy and safety of tedizolid phosphate, an oxazolidinone drug, for the treatment of gram-positive ventilated hospital-acquired bacterial pneumonia (vHABP)/ventilator-associated bacterial pneumonia (VABP) compared with linezolid (VITAL study), have been previously reported. We conducted a subgroup analysis to report the data obtained from Japanese patients enrolled in this study. MethodsPatients aged ≥18 years with vHABP/VABP likely to be caused by gram-positive cocci were randomized 1:1 to tedizolid phosphate 200 mg once daily for 7 days or linezolid 600 mg twice daily for 10 days. In both treatment groups, patients with concurrent gram-positive bacteremia were treated for 14 days. Primary efficacy endpoints were day 28 all-cause mortality (ACM) and investigator-assessed clinical response at test-of-cure (TOC) in the intention-to-treat population. Safety outcomes included assessment of treatment-emergent adverse events. ResultsFifty-three Japanese patients were randomized at received study drug (tedizolid, n = 28; linezolid, n = 25). Demographics and characteristics were generally similar between treatment groups. Rates of day 28 ACM were 10.7% and 20.0% with tedizolid and linezolid, respectively (difference, 9.3%; 95% CI, −10.1 to 28.7). Rates of investigator-assessed clinical cure at TOC were 78.6% and 72.0% with tedizolid and linezolid, respectively (difference, 6.6%; 95% CI, −16.7 to 29.8). Tedizolid phosphate was generally well tolerated and no new safety concerns were observed in the Japanese subgroup. ConclusionThe results from this subgroup analysis suggest generally favorable efficacy and safety of tedizolid in adult Japanese patients with vHABP/VABP. (ClinicalTrials.gov identifier: NCT02019420).

Efficacy and Safety of Omadacycline Versus Linezolid in Acute Bacterial Skin and Skin Structure Infections in Persons Who Inject Drugs.

IntroductionAcute bacterial skin and skin structure infections (ABSSSI) represent one of the most common reasons for emergency department visits, and are frequent complications of intravenous drug use in persons who inject drugs (PWID). This study examined the efficacy and safety of omadacycline, versus linezolid, in PWID and persons who do not inject drugs, in the Phase 3 Omadacycline in Acute Skin and Skin Structure Infection (OASIS-1, OASIS-2) studies.MethodsEligible participants were aged ≥ 18 years with qualifying skin infections: wound infection, cellulitis, erysipelas, or major abscess. The primary efficacy endpoint was early clinical response (ECR) in the modified intent-to-treat (mITT) population, defined as survival with ≥ 20% reduction in lesion size at 48–72 h after the first dose of omadacycline or linezolid. Key secondary endpoints included investigator-assessed clinical response at the post-treatment evaluation (PTE) in the mITT and clinical per-protocol populations, and clinical response at PTE in the micro-mITT population. Safety was assessed based on adverse events (AEs) and standard clinical laboratory tests. Efficacy endpoints of clinical response at ECR and PTE were analyzed for the mITT and clinically evaluable (CE) PTE populations.ResultsIn total, 1380 patients (822 PWID, 558 non-PWID) were included in this secondary analysis. Wound infections were reported more frequently in the PWID subgroup (72.8%) at baseline; cellulitis or erysipelas (43.9%) and major abscess (37.4%) were the most frequently reported baseline infections in the non-PWID subgroup. Clinical success rates at ECR and PTE in the mITT population, and at PTE in the CE population, were high for patients receiving omadacycline or linezolid. Severe or serious treatment-emergent AEs (TEAEs), and TEAEs leading to discontinuation, were infrequent.ConclusionThis subgroup analysis showed that omadacycline was effective and well tolerated, regardless of PWID status.

Lefamulin in Patients with Community-Acquired Bacterial Pneumonia Caused by Atypical Respiratory Pathogens: Pooled Results from Two Phase 3 Trials.

Lefamulin was the first systemic pleuromutilin antibiotic approved for intravenous and oral use in adults with community-acquired bacterial pneumonia based on two phase 3 trials (Lefamulin Evaluation Against Pneumonia [LEAP]-1 and LEAP-2). This pooled analysis evaluated lefamulin efficacy and safety in adults with community-acquired bacterial pneumonia caused by atypical pathogens (Mycoplasma pneumoniae, Legionella pneumophila, and Chlamydia pneumoniae). In LEAP-1, participants received intravenous lefamulin 150 mg every 12 h for 5–7 days or moxifloxacin 400 mg every 24 h for 7 days, with optional intravenous-to-oral switch. In LEAP-2, participants received oral lefamulin 600 mg every 12 h for 5 days or moxifloxacin 400 mg every 24 h for 7 days. Primary outcomes were early clinical response at 96 ± 24 h after first dose and investigator assessment of clinical response at test of cure (5–10 days after last dose). Atypical pathogens were identified in 25.0% (91/364) of lefamulin-treated patients and 25.2% (87/345) of moxifloxacin-treated patients; most were identified by ≥1 standard diagnostic modality (M. pneumoniae 71.2% [52/73]; L. pneumophila 96.9% [63/65]; C. pneumoniae 79.3% [46/58]); the most common standard diagnostic modality was serology. In terms of disease severity, more than 90% of patients had CURB-65 (confusion of new onset, blood urea nitrogen > 19 mg/dL, respiratory rate ≥ 30 breaths/min, blood pressure <90 mm Hg systolic or ≤60 mm Hg diastolic, and age ≥ 65 years) scores of 0–2; approximately 50% of patients had PORT (Pneumonia Outcomes Research Team) risk class of III, and the remaining patients were more likely to have PORT risk class of II or IV versus V. In patients with atypical pathogens, early clinical response (lefamulin 84.4–96.6%; moxifloxacin 90.3–96.8%) and investigator assessment of clinical response at test of cure (lefamulin 74.1–89.7%; moxifloxacin 74.2–97.1%) were high and similar between arms. Treatment-emergent adverse event rates were similar in the lefamulin (34.1% [31/91]) and moxifloxacin (32.2% [28/87]) groups. Limitations to this analysis include its post hoc nature, the small numbers of patients infected with atypical pathogens, the possibility of PCR-based diagnostic methods to identify non-etiologically relevant pathogens, and the possibility that these findings may not be generalizable to all patients. Lefamulin as short-course empiric monotherapy, including 5-day oral therapy, was well tolerated in adults with community-acquired bacterial pneumonia and demonstrated high clinical response rates against atypical pathogens.

Pooled microbiological findings and efficacy outcomes by pathogen in adults with community-acquired bacterial pneumonia from the Lefamulin Evaluation Against Pneumonia (LEAP) 1 and LEAP 2 phase 3 trials of lefamulin versus moxifloxacin

Lefamulin, a pleuromutilin antibiotic approved for community-acquired bacterial pneumonia (CABP), was evaluated for microbiological efficacy in a prespecified pooled analysis of LEAP 1 and 2 phase 3 clinical trial data in patients with CABP. In LEAP 1, adults (PORT risk class III‒V) received intravenous (IV) lefamulin 150 mg every 12 h (q12h) for 5‒7 days or moxifloxacin 400 mg every 24 h (q24h) for 7 days, with optional IV-to-oral switch. In LEAP 2, adults (PORT II‒IV) received oral lefamulin 600 mg q12h for 5 days or moxifloxacin 400 mg q24h for 7 days. Primary outcomes were early clinical response (ECR) at 96 ± 24 h after treatment start and investigator assessment of clinical response (IACR) 5‒10 days after the last dose. Secondary outcomes included ECR and IACR in patients with a baseline CABP pathogen (detected via culture, urinary antigen testing, serology and/or real-time PCR). Baseline CABP pathogens were detected in 709/1289 patients (55.0%; microbiological intention-to-treat population). The most frequently identified pathogens were Streptococcus pneumoniae (61.9% of patients) and Haemophilus influenzae (29.9%); 25.1% had atypical pathogens and 33.1% had polymicrobial infections. Pathogens were identified most frequently by PCR from sputum, followed by culture from respiratory specimens. In patients with baseline CABP pathogens, ECR rates were 89.3% (lefamulin) and 93.0% (moxifloxacin); IACR success rates were 83.2% and 86.7%, respectively. Results were consistent across CABP pathogens, including drug-resistant isolates and polymicrobial infections. Lefamulin is a valuable IV and oral monotherapy option for empirical and directed CABP treatment in adults.

A Phase I Study of LSZ102, an Oral Selective Estrogen Receptor Degrader, with or without Ribociclib or Alpelisib, in Patients with Estrogen Receptor-Positive Breast Cancer.

Data are sparse for oral selective estrogen receptor (ER) degraders (SERD) in cancer treatment. The investigational oral SERD LSZ102 was assessed in monotherapy and combination use in a phase I study. A phase I, multicenter, open-label dose-escalation study (NCT02734615) of LSZ102 alone (arm A; n = 77) or with ribociclib (arm B; n = 78) or alpelisib (arm C; n = 43) in heavily pretreated adults with histologically confirmed ER-positive breast cancer and prior disease progression. Arm A received LSZ102 200-900 mg/day; arm B, LSZ102 200-600 mg/day plus ribociclib 300-600 mg/day; arm C, LSZ102 300-450 mg/day plus alpelisib 200-300 mg/day. Key outcomes were dose-limiting toxicities (DLT) in the first 28-day treatment cycle, adverse events (AE), laboratory parameters, pharmacokinetics, biopsy ER protein, and investigator-assessed clinical response (RECIST v1.1). The most common AEs were gastrointestinal. Treatment-related serious AEs occurred in 10% of participants (19/198), mostly in arm C [10/43 (23%)]. DLTs occurred in: arm A, 5% (4/77); arm B, 3% (2/78); and arm C, 19% (8/43). LSZ102 exposure was slightly greater than dose proportional. On-treatment biopsy ER reductions were observed, with a trend toward an LSZ102 dose response. Objective response rates (95% confidence interval) were: arm A, 1.3% (0.0-7.0); arm B, 16.9% (9.3-27.1); and arm C, 7.0% (1.5-19.1), and clinical benefit rates 7.8% (2.9-16.2), 35.1% (24.5-46.8), and 20.9% (10.0-36.0), respectively. LSZ102 was well tolerated alone and with ribociclib and had a manageable safety profile with alpelisib. Preliminary clinical activity was observed in combination use.

Effectiveness and Safety of Compound Polymyxin B Ointment in Treatment of Burn Wounds: A Meta-analysis.

Burn injuries represent a global public health concern. The guidelines for burn care mention that the treatment of burn injuries depends on the type of burn injury, depth of tissue, area of wounds, and site on the body. At present, several topical antimicrobial agents are used in the treatment of burn wounds as a first choice. This study aims to investigate the effectiveness of the compound polymyxin B topical agents for the treatment of burn wounds. PubMed, Web of Science, ProQuest, and China National Knowledge Infrastructure databases were searched for articles published until January 2021. The studies that conducted clinical trials comparing compound polymyxin B ointment with other treatment reagents for burn wound treatment were included. A total of three outcomes, which were investigator-assessed clinical response, including mortality, bacterial counts, efficacy and safety were included for analysis in this study. In total, 12 randomized controlled trials, 1 clinical trial, 2 prospective studies, and 1 retrospective study were extracted. The result of mortality showed no significant difference (risk ratio [RR]: 0.70, 95% CI: 0.21-2.31, P = .56); wound healing revealed an RR of 1.59 (95% CI: 1.40-1.81, P < .001); time to heal revealed a mean difference of -5.09 (95% CI: -6.31 to -3.86) days (P < .001); scar incidence was not significantly lower in the treatment group (RR: 0.70, 95% CI: 0.38-1.30, P = .26); and adverse event incidence was significantly lower in the treatment group (RR: 0.26, 95% CI: 0.09-0.72, P < .01). The compound polymyxin B ointment shows the effectiveness of increase in the wound healing and accelerates the time of healing with fewer adverse effects.

Clinical effectiveness of olaparib monotherapy in germline BRCA-mutated, HER2-negative metastatic breast cancer in a real-world setting: phase IIIb LUCY interim analysis

BackgroundIn the phase III OlympiAD trial, olaparib significantly increased progression-free survival (PFS) compared with chemotherapy of physician's choice in patients with germline BRCA-mutated (gBRCAm), human epidermal growth factor 2 (HER2)-negative metastatic breast cancer (mBC). The phase IIIb LUCY trial assessed the clinical effectiveness of olaparib in similar patients, in a setting reflecting clinical practice. MethodsThis open-label, single-arm trial of olaparib (300 mg, twice daily) enrolled patients with BRCAm, HER2-negative mBC who had received taxane and/or anthracycline in the (neo)adjuvant/metastatic setting and not more than two lines of prior chemotherapy for mBC. Patients with hormone receptor–positive mBC had progressed on at least one line of endocrine therapy in an adjuvant/metastatic setting and were unsuitable for further endocrine treatment. This interim analysis was planned after 160 PFS events. ResultsOf 563 patients screened, 252 patients with gBRCAm were enrolled and received at least one dose of olaparib. The median investigator-assessed PFS was 8.11 months (95% confidence interval [CI], 6.93–8.67; 166/252 events [65.9% maturity]). The investigator-assessed clinical response rate was 48.6%, and median time to first subsequent treatment or death was 9.66 months (95% CI, 8.67–11.14). The most common treatment-emergent adverse events (TEAEs; >20% patients) were nausea, anaemia, asthenia, vomiting and fatigue. Eleven patients (4.4%) discontinued treatment because of a TEAE. Grade 3 or higher TEAEs occurred in 64 patients (25.4%), including anaemia (33 patients; 13.1%). ConclusionOlaparib was clinically effective in patients with gBRCAm, HER2-negative mBC with safety outcomes consistent with previous findings. ClinicalTrials.gov identifier: NCT03286842.

Lefamulin efficacy and safety in a pooled phase 3 clinical trial population with community-acquired bacterial pneumonia and common clinical comorbidities

BackgroundLefamulin, a first-in-class pleuromutilin antibiotic approved for intravenous and oral use in adults with community-acquired bacterial pneumonia (CABP), was noninferior to moxifloxacin in the Lefamulin Evaluation Against Pneumonia (LEAP) 1 intravenous-to-oral switch study and the LEAP 2 oral-only study. Using pooled LEAP 1/2 data, we examined lefamulin efficacy/safety overall and within subgroups of patients presenting with comorbidities typical in CABP management.MethodsIn LEAP 1, adults with CABP were randomized to receive intravenous lefamulin (150 mg every 12 h) for 5‒7 days or moxifloxacin (400 mg every 24 h) for 7 days, with optional intravenous-to-oral switch if predefined improvement criteria were met. In LEAP 2, adults with CABP were randomized to receive oral lefamulin (600 mg every 12 h) for 5 days or moxifloxacin (400 mg every 24 h) for 7 days. Both studies assessed early clinical response (ECR) at 96 ± 24 h after first study drug dose and investigator assessment of clinical response (IACR) at test-of-cure (5‒10 days after last dose). Pooled analyses of the overall population used a 10% noninferiority margin.ResultsLefamulin (n = 646) was noninferior to moxifloxacin (n = 643) for ECR (89.3% vs 90.5%, respectively; difference − 1.1%; 95% CI − 4.4 to 2.2); IACR success rates at test-of-cure were similarly high (≥ 85.0%). High efficacy with both lefamulin and moxifloxacin was also demonstrated across all well-represented patient subgroups, including those with advanced age, diabetes mellitus, a history of cardiovascular diseases (e.g., hypertension, congestive heart failure, or arrhythmia) or chronic lung diseases (e.g., asthma or chronic obstructive pulmonary disease), elevated liver enzymes, or mild-to-moderate renal dysfunction. No new safety signals were identified.ConclusionsLefamulin may provide a valuable intravenous/oral monotherapy alternative to fluoroquinolones or macrolides for empiric treatment of patients with CABP, including cases of patients at risk for poor outcomes due to age or various comorbidities.Trial registrationClinicalTrials.gov LEAP 1 (NCT02559310; Registration Date: 24/09/2015) and LEAP 2 (NCT02813694; Registration Date: 27/06/2016).

A Phase 3, Randomized, Double-Blind Study Comparing Tedizolid Phosphate and Linezolid for Treatment of Ventilated Gram-Positive Hospital-Acquired or Ventilator-Associated Bacterial Pneumonia.

BackgroundHospital-acquired bacterial pneumonia (HABP) and ventilator-associated bacterial pneumonia (VABP) are associated with high mortality rates. We evaluated the efficacy and safety of tedizolid (administered as tedizolid phosphate) for treatment of gram-positive ventilated HABP/VABP.MethodsIn this randomized, noninferiority, double-blind, double-dummy, global phase 3 trial, patients were randomized 1:1 to receive intravenous tedizolid phosphate 200 mg once daily for 7 days or intravenous linezolid 600 mg every 12 hours for 10 days. Treatment was 14 days in patients with concurrent gram-positive bacteremia. The primary efficacy end points were day 28 all-cause mortality (ACM; noninferiority margin, 10%) and investigator-assessed clinical response at test of cure (TOC; noninferiority margin, 12.5%) in the intention-to-treat population.ResultsOverall, 726 patients were randomized (tedizolid, n = 366; linezolid, n = 360). Baseline characteristics, including incidence of methicillin-resistant Staphylococcus aureus (31.3% overall), were well balanced. Tedizolid was noninferior to linezolid for day 28 ACM rate: 28.1% and 26.4%, respectively (difference, –1.8%; 95% confidence interval [CI]: –8.2 to 4.7). Noninferiority of tedizolid was not demonstrated for investigator-assessed clinical cure at TOC (tedizolid, 56.3% vs linezolid, 63.9%; difference, –7.6%; 97.5% CI: –15.7 to 0.5). In post hoc analyses, no single factor accounted for the difference in clinical response between treatment groups. Drug-related adverse events occurred in 8.1% and 11.9% of patients who received tedizolid and linezolid, respectively.ConclusionsTedizolid was noninferior to linezolid for day 28 ACM in the treatment of gram-positive ventilated HABP/VABP. Noninferiority of tedizolid for investigator-assessed clinical response at TOC was not demonstrated. Both drugs were well tolerated.Clinical Trials RegistrationNCT02019420.

Omadacycline vs moxifloxacin in adults with community-acquired bacterial pneumonia

ObjectiveCommunity-acquired bacterial pneumonia (CABP) is a major clinical burden worldwide. In the phase III OPTIC study (NCT02531438) in CABP, omadacycline was found to be non-inferior to moxifloxacin for investigator-assessed clinical response (IACR) at post-treatment evaluation (PTE, 5–10 days after last dose). This article reports the efficacy findings, as specified in the European Medicines Agency (EMA) guidance. MethodsPatients were randomized 1:1 to omadacycline 100 mg intravenously (every 12 h for two doses, then every 24 h) with optional transition to 300 mg orally after 3 days, or moxifloxacin 400 mg intravenously (every 24 h) with optional transition to 400 mg orally after 3 days. The total treatment duration was 7−14 days. The primary endpoint for EMA efficacy analysis was IACR at PTE in patients with Pneumonia Patient Outcomes Research Team (PORT) risk class III and IV. ResultsIn total, 660 patients were randomized as PORT risk class III and IV. Omadacycline was non-inferior to moxifloxacin at PTE. The clinical success rates were 88.4% and 85.2%, respectively [intent-to-treat population; difference 3.3; 97.5% confidence interval (CI) −2.7 to 9.3], and 92.5% and 90.5%, respectively (clinically evaluable population; difference 2.0; 97.5% CI 3.2–7.4). Clinical success rates with omadacycline and moxifloxacin were similar against identified pathogens and across key subgroups. ConclusionsOmadacycline was non-inferior to moxifloxacin for IACR at PTE, with high clinical success across pathogen types and patient subgroups.

637. Outcomes by Body Mass Index (BMI) in the STRIVE Phase 2 Trial of Once-Weekly Rezafungin for Treatment of Candidemia and Invasive Candidiasis Compared with Caspofungin

BackgroundThere is increasing evidence of antifungal underdosing in the treatment of invasive disease, particularly in special populations such as the obese. Body size is often an important variable affecting drug exposure, and pharmacokinetic (PK) models of antifungal dosing have suggested size-based dose adjustments to achieve target drug exposure.Rezafungin (RZF) is a novel echinocandin in Phase 3 development for treatment of candidemia and invasive candidiasis (IC) and for prevention of invasive fungal disease caused by Candida, Aspergillus, and Pneumocystis in blood and marrow transplant recipients. Distinctive PK properties of RZF (e.g., long half-life, extensive tissue distribution, and front-loaded drug exposure) lend themselves to RZF once-weekly (QWk) dosing and antifungal efficacy. In this sub-analysis of the Phase 2 STRIVE trial of RZF in the treatment of candidemia and/or IC, outcomes based on patient BMI were evaluated.MethodsThe STRIVE trial (NCT02734862) compared the safety and efficacy of RZF QWk compared with once-daily caspofungin (Fig. 1). For this subanalysis, data were stratified by BMI categories of < 30 kg/m2 and ≥ 30 kg/m2. Efficacy (overall response [resolution of clinical signs of infection + mycological eradication], mycological response, and investigator assessment of clinical response) and safety (treatment-emergent adverse events [TEAEs]) endpoints by treatment group were evaluated, as well as PK data (area under the curve [AUC]) from RZF-treated patients.Figure 1. ResultsMean BMI values were similar across treatment arms (26.9 kg/m2 in RZF Group 1 and 26.8 kg/m2 in RZF Group 2 and CAS arms). Efficacy outcomes at Day 14 were similar between BMI categories (Table 1). Rates of TEAEs were generally similar between BMI categories as well (Table 2), with no concerning safety trends. Following one dose of RZF 400 mg (Week 1), the ranges of AUCs by BMI category overlapped and there was a minor mean difference of ~20% (lower for those with BMI ≥ 30 kg/m2) (Fig. 2).Table 1 Table 2 Figure 2. ConclusionThe safety, efficacy, and PK of RZF in the Phase 2 STRIVE trial was consistent across BMI categories. These results suggest that dose adjustments in obese patients are not necessary. These findings contribute to the evaluation of RZF in a range of patient populations and its ongoing development.Disclosures Shawn Flanagan, PhD, Cidara Therapeutics, Inc. (Employee, Shareholder) Peter Pappas, MD, SCYNEXIS, Inc. (Consultant, Advisor or Review Panel member, Research Grant or Support) Taylor Sandison, MD, MPH, Cidara Therapeutics, Inc. (Employee, Shareholder) Patrick M. Honore, MD, PhD, FCCM, Cidara Therapeutics, Inc. (Scientific Research Study Investigator)

LEFAMULIN EFFICACY AND SAFETY IN ADULTS WITH COMMUNITY-ACQUIRED BACTERIAL PNEUMONIA: POOLED ANALYSIS OF THE LEFAMULIN EVALUATION AGAINST PNEUMONIA (LEAP) 1 AND LEAP 2 TRIALS BY AGE, INCLUDING IN PATIENTS AGED ≥85 YEARS

SESSION TITLE: Chest Infections Posters SESSION TYPE: Original Investigation Posters PRESENTED ON: October 18-21, 2020 PURPOSE: Community-acquired bacterial pneumonia (CABP) is the most common cause of infectious death in US adults aged >65y. Worldwide, the aging population is increasing, and older patients (pts) with CABP are especially at risk, with higher hospitalization and mortality rates than younger pts. Those with advanced age are more vulnerable to having or developing CABP complications, and treatment is often more difficult in these pts (eg, due to multimorbidity, immunosenescence, polypharmacy). The efficacy/safety of lefamulin (LEF), a novel pleuromutilin approved for intravenous (IV) and oral use in adults with CABP, were shown in 2 noninferiority phase 3 trials, LEAP 1 and LEAP 2. Here, we report pooled LEAP 1 and 2 efficacy/safety outcomes by age group (18-64, 65-74, 75-84, and ≥85y). METHODS: In LEAP 1, adults with CABP (PORT risk class III–V) received IV LEF 150mg q12h for 5–7d or moxifloxacin (MOX) 400mg q24h for 7d, with optional IV-to-oral switch (LEF 600mg q12h or MOX 400mg q24h). In LEAP 2, adults with CABP (PORT II–IV) received oral LEF 600mg q12h (5d) or MOX 400mg q24h (7d). Both studies assessed early clinical response (ECR) at 96±24h after first study drug dose in the intent-to-treat (ITT) population (all randomized pts) and investigator assessment of clinical response (IACR) at test of cure (TOC; 5–10d after last dose) in the modified ITT (received ≥1 study drug dose) and clinically evaluable (met predefined evaluability criteria) populations. Treatment-emergent adverse events (TEAEs) were also assessed. RESULTS: In the pooled ITT population, 1289 pts were randomized to LEF (n=646) or MOX (n=643); 772 (59.9%) were aged 18–64y, 297 (23.0%) were 65–74y, 177 (13.7%) were 75–84y, and 43 (3.3%) were ≥85y. Older pts (ages 75–84y, ≥85y) were more likely to have comorbidities (eg, moderate/severe renal impairment, hypertension, arrhythmia) vs younger pts (ages 18–64y, 65–74y). For all age groups, high and similar ECR (LEF ≥88%; MOX ≥82%) and IACR success (LEF ≥82%; MOX ≥83%) rates were seen with each treatment, including in pts aged ≥85y (ECR: 88.5% [LEF] vs 82.4% [MOX]; IACR success: 88.5%-95.5% vs 88.2%-100%). The most common TEAEs were gastrointestinal, with generally similar rates across age groups for LEF (8.6%–15.0%) and MOX (5.9%–14.0%). With both treatments, rates of serious TEAEs and TEAEs leading to death were somewhat lower in younger (3.4%–5.3% and 0.5%–2.6%, respectively) vs older (5.9%–12.4% and 0%–4.5%) pts. Rates of study drug discontinuation due to TEAEs were similar for older (3.5%) and younger (3.0%) pts with LEF, while rates with MOX were higher in older (7.8%) vs younger (2.4%) pts. CONCLUSIONS: LEF efficacy was high across all age groups, including pts aged ≥85y. The AE profile and study drug discontinuation rates were similar across all age groups. CLINICAL IMPLICATIONS: LEF is a promising new option for treating CABP in pts with advanced age and comorbidities at risk of poor outcomes. DISCLOSURES: Employee relationship with Vir Biotech Please note: >$100000 Added 06/12/2020 by Elizabeth Alexander, source=Web Response, value=Salary Former Employee, Holds Stock relationship with Nabriva Therapeutics Please note: $1001 - $5000 Added 06/12/2020 by Elizabeth Alexander, source=Web Response, value=Company Stock Employee relationship with Nabriva Therapeutics Please note: >$100000 Added 06/01/2020 by Steven Gelone, source=Web Response, value=Salary Employee relationship with Nabriva Therapeutics Please note: >$100000 Added 06/01/2020 by Steven Gelone, source=Web Response, value=Ownership interest Employee relationship with Nabriva Therapeutics Please note: >$100000 Added 04/15/2020 by Lisa Goldberg, source=Web Response, value=Salary Employee relationship with Nabriva Therapeutics Please note: $20001 - $100000 Added 04/15/2020 by Lisa Goldberg, source=Web Response, value=Stock Employee relationship with Nabriva Therapeutics Please note: >$100000 Added 04/08/2020 by Andrew Meads, source=Web Response, value=Salary Employee relationship with Nabriva Therapeutics Please note: $5001 - $20000 Added 04/08/2020 by Andrew Meads, source=Web Response, value=Shareholder Consultant relationship with Allergan and Nabriva Therapeutics Please note: $1-$1000 Added 04/07/2020 by Christian Sandrock, source=Web Response, value=Consulting fee Removed 04/07/2020 by Christian Sandrock, source=Web Response Consultant relationship with Allergan Please note: $1-$1000 Added 04/07/2020 by Christian Sandrock, source=Web Response, value=Consulting fee Consultant relationship with Nabriva Therapeutics Please note: $1-$1000 Added 04/07/2020 by Christian Sandrock, source=Web Response, value=Consulting fee Employee relationship with Nabriva Therapeutics Please note: >$100000 Added 06/02/2020 by Jennifer Schranz, source=Web Response, value=Salary

Real-world clinical effectiveness and safety of olaparib monotherapy in HER2-negative gBRCA-mutated metastatic breast cancer: Phase IIIb LUCY interim analysis.

1087 Background: OlympiAD (NCT02000622) demonstrated the benefit of olaparib over standard of care in patients (pts) with HER2-negative (HER2-) metastatic breast cancer (MBC) and germline BRCA mutations (gBRCAm). LUCY (NCT03286842) aimed to provide additional data on the real-world effectiveness and safety of olaparib monotherapy in this setting. Methods: This Phase IIIb, open-label, single-arm study of olaparib 300 mg twice-daily, enrolled pts with HER2- gBRCAm MBC who had received a taxane and/or anthracycline in the (neo)adjuvant/metastatic setting, and ≤2 lines of chemotherapy for MBC. Hormone receptor-positive (HR+) pts had progressed on prior endocrine therapy (ET), and further ET was considered unsuitable. Primary endpoint: investigator-defined progression-free survival (PFS). Secondary endpoints: overall survival, time to first subsequent therapy or death (TFST), and investigator-assessed clinical response rate (CRR). The interim analysis was planned after 160 PFS events. Results: From Oct 2018-Sept 2019, 252 pts were enrolled (160 sites, 15 countries; mean age 46.2 [range 22-75] years; 73.4% ECOG PS 0). Median total treatment duration: 7.9 months (mo; range 0.2-20.0). Median PFS: 8.1 mo (95% confidence interval [CI] 6.9, 8.7; 166 events [65.9%]). Clinical trial information: NCT03286842 . Median TFST: 9.7 mo (95% CI 8.7, 11.1). CRR: 48.6% (95% CI 42.2, 55.0). Adverse events (AEs) in &gt;20% of pts (all grades): nausea, anemia, asthenia, vomiting, and fatigue. 24.6% of pts reported a grade ≥3 AE, including anemia (n=33 [13.1%]). 4.4% of pts had an AE leading to treatment discontinuation. Conclusions: Interim results in this real-world population of pts with HER2- gBRCAm MBC were consistent with the OlympiAD study, and support olaparib as a chemotherapy-free alternative treatment for pts with gBRCAm advanced BC. [Table: see text]

664. Efficacy in Adults With Moderate to Severe Community-Acquired Bacterial Pneumonia (CABP) and Pneumonia Outcomes Research Team (PORT) Risk Class III to V: Results of a Pooled Analysis of Lefamulin Evaluation Against Pneumonia (LEAP) 1 and LEAP 2 Study Outcomes

BackgroundCABP, the second most common cause of hospitalization in the US, has prognoses ranging from rapid resolution to death, the likelihood of which can be estimated via PORT pneumonia severity index. Patients with PORT scores ≤III have predicted mortality rates <3% and may be managed as outpatients; those with scores of IV/V are often hospitalized, owing to higher predicted mortality rates (8%–31%). Lefamulin (LEF), a novel systemic antibiotic, was noninferior to moxifloxacin (MOX) for treatment of adults with CABP in 2 phase 3 trials (LEAP 1 and 2). We report the results of pooled analyses of LEAP 1/2 data in patients with PORT III and IV/V scores.MethodsIn LEAP 1, patients (PORT III–V) received IV LEF 150 mg for 5–7 d or MOX 400 mg for 7 d, with optional IV-to-oral switch. In LEAP 2, patients (PORT II–IV) received oral LEF 600 mg for 5 d or MOX 400 mg for 7 d. In both studies, randomization was stratified by PORT score. The studies assessed early clinical response (ECR; 96±24 h after first dose) in the intent-to-treat (ITT; all randomized patients) population (FDA primary endpoint) and investigator assessment of clinical response (IACR) success at test of cure (5–10 d after last dose) in the modified ITT (received ≥1 dose) and clinically evaluable (met predefined evaluability criteria) populations (EMA coprimary endpoints).ResultsOver 50% of patients (52.8% LEF; 51.9% MOX) were PORT III and >18% (18.7% LEF; 18.2% MOX) were PORT IV/V, reflective of the CABP population. As expected, PORT IV/V patients were older and more likely to have comorbidities (eg, moderate/severe renal impairment) vs. PORT III patients (Table 1). ECR and IACR response rates were high and similar for LEF and MOX in PORT III (Figure 1) and PORT IV/V (Figure 2) patients, with slightly higher rates in PORT III vs. PORT IV/V patients. LEF and MOX had similar safety profiles, with more adverse events overall in PORT IV/V vs. PORT III patients (Table 2). Mortality rates were low, with higher rates in PORT IV/V (4.2% LEF; 5.2% MOX) vs. PORT III (1.5% LEF; 0.6% MOX) patients.ConclusionECR and IACR rates with LEF were high and similar to MOX in patients who are candidates for outpatient (PORT III) and inpatient (PORT IV/V) treatment; LEF may be an alternative oral and IV monotherapy option for empiric CABP treatment in both populations. Disclosures All authors: No reported disclosures.

2233. Efficacy and Symptom Resolution by Visit in Adults With Community-Acquired Bacterial Pneumonia (CABP) Treated With Lefamulin (LEF) or Moxifloxacin (MOX): Pooled Analysis of Lefamulin Evaluation Against Pneumonia (LEAP) 1 and LEAP 2 Study Results

BackgroundEfficacy and safety of LEF were shown in 2 noninferiority trials (LEAP 1/2) vs. MOX in adults with CABP. We assessed the efficacy of LEF by visit based on a pooled analyses of LEAP 1/2 data.MethodsIn LEAP 1, PORT III–V patients (patients) received LEF 150 mg IV q12h for 5–7 days or MOX 400 mg IV q24h for 7 days, with optional IV-to-oral switch (600 mg LEF q12h or 400 mg MOX q24h). In LEAP 2, PORT II–IV patients received oral LEF 600 mg q12h for 5 days or oral MOX 400 mg q24h for 7 days. Criteria for defining the FDA primary endpoint of early clinical response (ECR) at 96 ± 24 hours after first dose were applied to each visit through late follow-up (LFU; days 27–34) in the intent-to-treat (ITT; all randomized patients) population. Investigator assessment of clinical response (IACR) was examined at end of treatment (EOT; within 2 days after last dose), test-of-cure (TOC; 5–10 days after last dose; EMA primary endpoint), and LFU in the modified ITT (mITT; received ≥1 dose of study drug) and clinically evaluable (CE; met predefined evaluability criteria) populations. Results are presented by visit for pooled LEAP 1/2 data.Results1289 ITT patients were randomized (LEF, n = 646; MOX, n = 643). Most patients in both groups achieved ECR at Day 3, with further increases through Day 7 and sustained efficacy through LFU (Fig 1). In mITT patients, IACR success rates at EOT/TOC/LFU were 87.1/85.0/83.2% with LEF and 88.1/87.1/86.1% with MOX; results were consistent in CE patients. The proportions of ITT patients with resolution of all baseline signs/symptoms of CABP increased similarly by visit in both treatment groups (Fig 2). Most patients did not achieve complete sign/symptom resolution until TOC, with fever generally being the first and cough the last to resolve. There was no apparent relationship between ECR and age, gender, renal status, SIRS, PORT, prior antibiotic use, baseline pathogens, typical/atypical pathogens, or mono/polymicrobial pathogens. The high percentage of patients at LFU with baseline symptom resolution suggests that symptom resolution was sustained.ConclusionIn this pooled analysis, efficacy results were similar by visit in the LEF and MOX groups, with high ECR rates maintained through LFU. LEF will provide a potential new effective systemic monotherapy alternative to fluoroquinolones for the empiric treatment of CABP. Disclosures All authors: No reported disclosures.

663. Efficacy and Safety of Lefamulin (LEF) vs. Moxifloxacin (MOX) for Legionella pneumophila (LP) in Patients with Community-Acquired Bacterial Pneumonia (CABP): Pooled Results From the Lefamulin Evaluation Against Pneumonia (LEAP) 1 and LEAP 2 Phase 3 Clinical Trials

Background LP is associated with severe CABP, rapid onset, and high morbidity/mortality. Poor outcomes in CABP have been linked to receiving inappropriate empiric therapy or delayed treatment (tx). LEF, a novel IV/oral pleuromutilin, demonstrated efficacy/safety in noninferiority studies (LEAP 1/2) vs. MOX in adults with CABP. We report efficacy/safety of LEF in patients with LP based on a pooled analyses of LEAP 1/2 data.MethodsIn LEAP 1, PORT III–V patients received LEF 150 mg IV q12h for 5–7 days or MOX 400 mg IV q24h for 7 days, with optional IV-to-oral switch (600 mg LEF q12h or 400 mg MOX q24h). In LEAP 2, PORT II–IV patients received oral LEF for 5 days or oral MOX for 7 days. Both studies assessed early clinical response (ECR) at 96 ± 24 hours after first dose in the intent-to-treat (ITT; all randomized patients) population and investigator assessment of clinical response (IACR) at test-of-cure (TOC; 5–10 days after last dose) in the modified ITT (received ≥1 dose) and clinically evaluable (met predefined evaluability criteria) populations. LP was identified from baseline (BL) samples by culture, serology (IgG, Zeus L. pneumophila group 1–6 indirect fluorescent antibody assay), urine antigen testing (BinaxNOW), and real-time PCR (positive for ssrA). Efficacy analyses herein were done in the microbiological ITT (microITT, treated patients with BL CABP-causing pathogen), microITT-2 (no PCR), and microbiologically evaluable populations; safety analyses included all randomized/treated patients.ResultsOf 65 pooled microITT patients, median age was 60 y, 66% were male, 51% had a normal renal function, and 54%/25% were PORT III/IV. LP was identified in 9.3% (34/364) of LEF patients (7 [20.6%]/19 [55.9%]/8 [23.5%] PORT II/III/IV) and in 9.0% (31/345) of MOX patients (7 [22.6%]/16 [51.6%]/8 [25.8%] PORT II/III/IV), primarily by urine antigen or serology (table). Patients with LP in both tx groups achieved high and similar responses across all endpoints (Figures 1 and 2). In both tx groups, TEAE rates were low and comparable (~32%) and most were mild to moderate; 5 patients (3 LEF; 2 MOX) had treatment-emergent SAEs, all unrelated to tx. No patients died due to TEAEs; no LEF patients and 2 MOX patients discontinued tx due to TEAEs.ConclusionLEF appears to be as safe and effective as MOX in treating patients with LP, including when given as short-course (5 days) oral therapy. Disclosures All authors: No reported disclosures.

717. Lefamulin (LEF) vs. Moxifloxacin (MOX) in Patients With Community-Acquired Bacterial Pneumonia (CABP) at Risk for Poor Efficacy or Safety Outcomes: Pooled Subgroup Analyses From the Lefamulin Evaluation Against Pneumonia (LEAP) 1 and LEAP 2 Phase 3 Noninferiority Clinical Trials

BackgroundIn the United States, CABP is the second most common cause of hospitalization and a leading cause of infectious death. Patients with chronic obstructive pulmonary disease (COPD)/asthma or diabetes are at risk for CABP and associated mortality. Similarly, patients with underlying cardiac or liver disease are at risk for potential cardiac or liver toxicities, respectively, associated with CABP antimicrobials, and patients aged ≥65 years are at risk for both efficacy/safety concerns. We report pooled efficacy/safety outcomes in at-risk subgroups from the LEAP 1 and 2 phase 3 trials.MethodsIn LEAP 1, patients with CABP (PORT III–V) received IV LEF 150 mg q12h for 5–7 days or MOX 400mg q24h for 7 days, with optional IV-to-oral switch (600 mg LEF q12h or 400 mg MOX q24h). In LEAP 2, patients with CABP (PORT II–IV) received oral LEF 600 mg q12h for 5 days or MOX 400 mg q24h for 7 days. Both studies assessed early clinical response (ECR; 96 ± 24 hours after first dose) in the intent-to-treat (ITT; all randomized patients) population (FDA primary endpoint) and investigator assessment of clinical response (IACR) at test-of-cure (TOC; 5–10 days after last dose) in the modified ITT (≥1 study drug dose) and clinically evaluable (met predefined evaluability criteria) populations (EMA coprimary endpoints). Pooled analyses used a 10% noninferiority margin. Safety was assessed in all randomized and treated patients.Results1289 ITT patients were randomized to LEF (n = 646) or MOX (n = 643); of whom, 297 (23.0%) were aged 65–74 years and 220 (17.1%) were ≥75 years; 232 patients (18.0%) had COPD/asthma and 168 (13.0%) had diabetes mellitus (DM). At baseline, 501 patients (38.9%) had history of hypertension, 73 (5.7%) had history of arrhythmia, and 263 (20.4%) had transaminitis. The figure shows efficacy by age and in COPD/asthma and DM patients. Treatment-emergent adverse events, electrocardiogram assessments, and laboratory results in patients at risk for cardiac and hepatic safety concerns are shown in Tables 1 and 2.ConclusionIn pooled analyses of LEAP 1 and 2, LEF efficacy was high and similar to MOX in patients at risk of efficacy concerns and LEF showed a safety profile similar to that of MOX in patients at risk of safety concerns. LEF is a promising new option for IV/oral monotherapy of CABP in patients at risk of poor outcomes due to CABP or to antimicrobial therapy for CABP. Disclosures All authors: No reported disclosures.

110. Clinical Outcomes of Patients with Secondary Bacteremia in the Omadacycline Phase 3 Acute Bacterial Skin and Skin Structure Infections and Community-Acquired Bacterial Pneumonia Studies

BackgroundLow serum concentrations of tetracycline antibiotics may raise concerns on their efficacy in patients with secondary bacteremia, especially in comorbid patients and in those with higher acuity of illness. Omadacycline (OMC), an aminomethylcycline antibiotic, showed noninferiority to linezolid (LZD) in two acute bacterial skin and skin structure infections (ABSSSI) studies (Omadacycline in Acute Skin and skin structure Infections Study [OASIS]-1 and -2), or to moxifloxacin (MOX) in a community-acquired bacterial pneumonia (CABP) study (Omadacycline for Pneumonia Treatment In the Community study [OPTIC]). This analysis considers clinical outcomes in patients with secondary bacteremia identified in these studies.MethodsBaseline blood cultures were taken from adult patients enrolled in Phase 3 randomized, double-blind clinical studies of OMC. Patients received ≥1 treatment dose: N = 1,347 ABSSSI (OMC n = 676; LZD n = 671); N = 774 CABP (OMC n = 386; MOX n = 388). Efficacy was evaluated by investigator assessment of clinical response at a post-treatment evaluation (PTE) 7–14 days (ABSSSI) or 5–10 days (CABP) after the last dose.ResultsBacteremia was confirmed in 63 patients (3%) across the three studies. Staphylococcus aureus was the most common pathogen in patients with ABSSSI (N = 30: OMC n/N = 7/13; LZD n/N = 9/17), with a median treatment duration of median 9 days (OMC) and median 10 days (LZD). Streptococcus pneumoniae was the most common pathogen in patients with CABP (N = 33; OMC n/N = 11/15; MOX n/N = 11/18), with a median treatment duration of 11 days (OMC) and 14 days (MOX). Clinical success was numerically comparable between treatment groups within each study (figure) after completion of therapy.ConclusionThe clinical successes of patients receiving OMC for ABSSSI or CABP with secondary bacteremia were comparable to results for LZD and MOX, respectively. Although limited by the small sample size, data from ABSSSI and CABP study patients with secondary bacteremia provide reassurance for the use of OMC. Real-world OMC data in patients with ABSSSI and CABP will be needed to assess outcomes in patients with additional comorbidities and/or higher acuity of illness. Disclosures All authors: No reported disclosures.