Response-evaluable Population Research Articles

Phase II study to determine the anti-tumor activity and safety of simlukafusp alfa (FAP-IL2v) combined with atezolizumab in esophageal cancer.

Reported here are results from the esophageal squamous cell carcinoma (SCC) cohort of a Phase II, non-comparative, basket study, evaluating the anti-tumor activity and safety of FAP-IL2v plus atezolizumab in patients with advanced/metastatic solid tumors (NCT03386721). Eligible patients had an Eastern Cooperative Oncology Group performance status of 0-1; measurable metastatic, persistent, or recurrent esophageal SCC; progression on ≥1 prior therapy; and were checkpoint inhibitor naive. Patients received FAP-IL2v 10 mg plus atezolizumab 1200 mg intravenously every 3 weeks, or FAP-IL2v weekly for 4 weeks, then every 2 weeks, plus atezolizumab 840 mg intravenously every 2 weeks. Primary endpoint was investigator-assessed objective response rate (ORR). In the response-evaluable population (N=34), best confirmed ORR was 20.6% (95% confidence interval [CI]: 10.4-36.8) with a complete response (CR) seen in one patient and partial responses (PR) in six patients. Disease control rate was 44.1% (CR=2.9%; PR=17.6%; stable disease [SD]=23.5%) and median duration of response was 10.1 months (95% CI: 5.6-26.7). Median progression-free survival was 1.9 months (95% CI: 1.8-3.7). Analysis of response by PD-L1 expression (Ventana SP263) resulted in an ORR of 26.7 % for patients with PD-L1-positive tumors (tumor area positivity [TAP] cut-off ≥1%; n=15) and 7.1% for patients with PD-L1-negative tumors (TAP cut-off <1%; n=14). Overall, the treatment combination was tolerable and adverse events were consistent with the known safety profiles of each drug. FAP-IL2v plus atezolizumab demonstrated clinical activity and was tolerable in patients with previously treated esophageal SCC.

Addition of daratumumab to lenalidomide, bortezomib, and dexamethasone for transplantation-eligible patients with newly diagnosed multiple myeloma (GRIFFIN): final analysis of an open-label, randomised, phase 2 trial

Addition of daratumumab to lenalidomide, bortezomib, and dexamethasone (D-RVd) in the GRIFFIN study improved the stringent complete response rate by the end of consolidation in transplantation-eligible patients with newly diagnosed multiple myeloma. Here, we report the findings of the predefined final analysis. GRIFFIN was an open-label, randomised, active-controlled, phase 2 trial done in 35 research centres in the USA. Patients had newly diagnosed multiple myeloma with measurable disease by M protein or free light chain, were aged 18-70 years, had an ECOG performance score of 0-2, and were eligible for autologous haematopoietic stem-cell transplantation (HSCT). Patients were randomly assigned (1:1) to four D-RVd or RVd induction cycles, autologous HSCT, two D-RVd or RVd consolidation cycles, and lenalidomide with or without daratumumab maintenance therapy for 2 years. Patients received 21-day cycles of oral lenalidomide (25 mg on days 1-14), subcutaneous bortezomib (1·3 mg/m2 on days 1, 4, 8, and 11), oral dexamethasone (40 mg weekly) with or without intravenous daratumumab (16 mg/kg weekly, cycles 1-4; day 1, cycles 5-6). Maintenance therapy (28-day cycles) was oral lenalidomide (10 mg on days 1-21) with or without daratumumab (16 mg/kg intravenously every 4 or 8 weeks, or 1800 mg subcutaneously monthly). Patients could continue lenalidomide maintenance after study treatment completion. The primary endpoint was stringent complete response rate by the end of consolidation in the response-evaluable population, and has already been reported. Here we report updated stringent complete response rates and secondary outcomes including progression-free survival and overall survival. The trial is registered with ClinicalTrials.gov (NCT02874742) and ended on April 8, 2022. Between Dec 20, 2016, and April 10, 2018, 104 patients were randomly assigned to the D-RVd group and 103 were randomly assigned to the RVd group; most patients were White (85 [82%] in the D-RVd group and 76 [74%] in the RVd group) and male (58 [56%] in the D-RVd group and 60 [58%] in the RVd group). At a median follow-up of 49·6 months (IQR 47·4-52·1), D-RVd improved rates of stringent complete response (67 [67%] of 100] vs 47 [48%] of 98]; odds ratio 2·18 [95% CI 1·22-3·89], p=0·0079), and 4-year progression-free survival was 87·2% (95% CI 77·9-92·8) for D-RVd versus 70·0% (95% CI 55·9-80·3) for RVd, with a hazard ratio (HR) of 0·45 (95% CI 0·21-0·95, p=0·032) for risk of disease progression or death with D-RVd. Median overall survival was not reached for either group (HR 0·90 [95% CI 0·31-2·56], p=0·84). The most common grade 3-4 treatment-emergent adverse events in the D-RVd versus RVd groups were neutropenia (46 [46%] of 99 vs 23 [23%] of 102), lymphopenia (23 [23%] vs 23 [23%]), leukopenia (17 [17%] vs eight [8%]), thrombocytopenia (16 [16%] vs nine [9%]), pneumonia (12 [12%] vs 14 [14%]), and hypophosphataemia (ten [10%] vs 11 [11%]). Serious treatment-emergent adverse events occurred in 46 (46%) of 99 patients in the D-RVd group and in 53 (52%) of 102 patients in the RVd group. One patient in each treatment group reported a treatment-emergent adverse event that resulted in death (bronchopneumonia in the D-RVd group; cause unknown in the RVd group); neither was related to study treatment. No new safety concerns occurred with maintenance therapy. Addition of daratumumab to RVd improved the depth of response and progression-free survival in transplantation-eligible patients with newly diagnosed multiple myeloma. These results justify further evaluation in phase 3 studies. Janssen Oncology.

Atezolizumab With or Without Radiotherapy for Advanced Squamous Cell Carcinoma of the Penis (The PERICLES Study): A Phase II Trial.

Patients with advanced penile squamous cell carcinoma have a poor prognosis (21% 2-year overall survival [OS] from diagnosis). We assessed the activity of atezolizumab (anti-PD-L1) in patients with advanced penile cancer, with or without radiotherapy (RT). A single-center, nonrandomized phase II study with two treatment arms was conducted in 32 patients with histologically confirmed advanced penile cancer. All patients received atezolizumab (1,200 mg) once every 3 weeks. Twenty patients, who were expected to benefit from RT for locoregional disease control, received additional irradiation. The primary end point was 1-year progression-free survival (PFS) for the complete cohort and was reached if the actual 1-year PFS was at least 35%. Secondary end points included OS, objective response rate (ORR), and tolerability. Exploratory biomarker analyses were conducted in pretreatment specimens. Median follow-up was 29.1 months (IQR, 18.1-33.5). Grade 3-4 adverse events related to atezolizumab or RT were observed in 3/32 (9.4%) and 13/20 (65%) patients, respectively. One-year PFS was 12.5% (95% CI, 5.0 to 31.3), which did not meet the study's primary end point. Median OS was 11.3 months (95% CI, 5.5 to 18.7). In the objective response-evaluable population (n = 30; 93.8%), the ORR was 16.7% (95% CI, 6 to 35), including 2 (6.7%) complete responders and 3 (10%) partial responders. Improved PFS was observed in patients with high-risk human papillomavirus (hrHPV)-positive tumors (P = .003) and those with high infiltration of intratumoral CD3+CD8+ T cells (P = .037). Although the primary end point of 1-year PFS was not met, durable antitumor activity to atezolizumab was observed in a subset of patients. Biomarkers, such as hrHPV and intratumoral CD3+CD8+ T-cell infiltration, may help to better select responders.

Mobocertinib efficacy in patients with NSCLC and EGFR exon 20 insertion mutations (ex20ins) identified by next-generation sequencing (NGS) of circulating tumor DNA (ctDNA).

9082 Background: EGFR ex20ins are distinct targetable driver mutations present in ~2% of all NSCLC. While most EGFR TKIs have limited effectiveness, mobocertinib is the first oral therapy approved for this unmet need. EGFR ex20ins are heterogeneous ( &gt; 60 variants), and PCR testing detects a limited number of variants, leading to undetected disease in ~50% of cases, whereas NGS can identify all such mutations. Testing plasma ctDNA is a noninvasive approach for detection of genomic variants, such as EGFR ex20ins. Methods: In the mobocertinib phase 1/2 study (NCT02716116), patients were enrolled based on EGFR ex20ins detected by various local tissue or liquid clinical trial assays (CTAs). Baseline plasma samples were collected and processed to extract cell-free DNA and were evaluated for EGFR ex20ins status using FoundationOne Liquid CDX (F1LCDX), an NGS-based plasma ctDNA test. Concordance between F1LCDX and the CTAs was demonstrated by testing patient samples from the phase 1/2 trial and paired tissue and plasma samples from commercially acquired and stage-matched patients with NSCLC (N = 305). Efficacy analyses by assay method were performed in EGFR ex20ins–positive platinum-pretreated patients (PPP; n = 114 [FDA approved population]; data cutoff: 1 Nov 2021) in the phase 1/2 trial. Results: Concordance between F1LCDX and CTAs was demonstrated with samples from the CTA-positive (n = 159) and CTA-negative populations (n = 87) tested by F1LCDX where tissue and plasma were assessable; the point estimate of positive percentage agreement (95% CI) was 68.6% (61.0–75.3), and the point estimate of negative percentage agreement was 100% (95.8–100). F1LCDX detected 34 individual EGFR ex20ins variant types. In the response evaluable population, patients who tested EGFR ex20ins positive by F1LCDX (n = 55) demonstrated confirmed ORR (34.5%) and disease control rate (74.5%), which was comparable to those observed among all PPP in the phase 1/2 trial (confirmed ORR: 28%; confirmed disease control rate: 78%). Conclusions: Mobocertinib has shown efficacy in PPP with EGFR ex20ins NSCLC. F1LCDX effectively identified patients with EGFR ex20ins who may benefit from mobocertinib, providing an additional noninvasive diagnostic option to guide treatment. Clinical trial information: NCT02716116 .

The iR2 regimen (ibrutinib plus lenalidomide and rituximab) for relapsed/refractory DLBCL: a multicentre, non-randomised, open-label phase 2 study

This phase 1b/2 PCYC-1123-CA study evaluated efficacy and safety of the combination of ibrutinib, lenalidomide, and rituximab (iR2 regimen) in patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) ineligible for stem cell transplantation. In phase 2, patients with relapsed/refractory non-germinal centre B-cell-like DLBCL received oral ibrutinib 560mg once daily and oral lenalidomide 20mg or 25mg once daily on Days 1-21 of each 28-day cycle until disease progression or unacceptable toxicity and intravenous rituximab 375mg/m2 on Day 1 of Cycles 1-6. The primary endpoint was overall response rate (ORR) in the response-evaluable population (received any study treatment and had ≥1 post-baseline disease assessment). The study was done at 24 academic and community hospitals in Belgium, Germany, United Kingdom, and USA. This study was registered with ClinicalTrials.gov, NCT02077166. Between March 13, 2014 and October 2, 2018, 89 patients were enrolled with a median time on study of 35.0 months. Best ORR in the response-evaluable population (n=85) was 49% (95% confidence interval [CI], 38-61) across dose cohorts and 53% (95% CI, 39-67) and 44% (95% CI, 26-62) in the 20mg and 25mg lenalidomide cohorts, respectively, with complete responses in 24/85 (28%), 17/53 (32%), and 7/32 (22%) patients, respectively. Grade 3/4 adverse events (AEs) occurred in 81/89 patients (91%), most frequently neutropenia (36/89; 40%), maculopapular rash (16/89; 18%), anaemia (12/89; 13%), and diarrhoea (9/89; 10%). Serious adverse events occurred in 57/89 patients (64%). Fatal AEs occurred in 12/89 patients (13%); causes of death were worsening of DLBCL (n=7), pneumonia (n=3), sepsis (n=1), and cardiac arrest (n=1). The most frequent AEs (diarrhoea, neutropenia, fatigue, cough, anaemia, peripheral oedema, and maculopapular rash) were consistent with known safety profiles of the individual drugs. The iR2 regimen demonstrated antitumour activity with durable responses in patients with relapsed/refractory DLBCL. Pharmacyclics LLC, an AbbVie Company.

Tazemetostat in Combination with Lenalidomide and Rituximab in Patients with Relapsed/Refractory Follicular Lymphoma: Phase 1b Results of Symphony-1

Background: The preferred second-line treatment for patients with relapsed/refractory (R/R) follicular lymphoma (FL) is either lenalidomide in combination with rituximab (R2) or an anti-CD20 antibody in combination with chemotherapy/immunotherapy. Tazemetostat (TAZ), an enhancer of zeste homolog 2 (EZH2) inhibitor, is approved by the US Food and Drug Administration for the treatment of patients with R/R FL whose disease has mutant (MT) EZH2 and who have received ≥2 prior therapies or who have no satisfactory alternative treatment options. EZH2 modulates the B-cell tumor microenvironment, supporting combination approaches to treatment. SYMPHONY-1 (EZH-302; NCT04224493) is a phase 1b/3 study designed to determine the recommended phase 3 dose (RP3D), efficacy, and safety of TAZ + lenalidomide and rituximab (R2) in patients with R/R FL after ≥1 prior therapy. We report the results after complete enrollment of the phase 1b safety run-in to assess safety and clinical activity of TAZ when administered with R2, including data for subsets of patients by mutation status, rituximab-refractory disease, and progression of disease in 24 months (POD24). Methods: Patients aged ≥18 years with histologically confirmed FL grade 1-3A who were previously treated with ≥1 prior systemic chemotherapy, immunotherapy, or chemoimmunotherapy were enrolled. The phase 1b portion enrolled patients regardless of EZH2 mutation status. Phase 1b evaluated TAZ at 3 dose levels (400, 600, and 800 mg orally twice daily [BID]) in 28-day cycles with standard-dose R2. Protocol-mandated dose modifications included simultaneous dose interruption and/or reduction of TAZ and lenalidomide for grade 3 neutropenia and thrombocytopenia. Primary endpoints of the phase 1b portion were safety and determination of the RP3D. Secondary endpoints included pharmacokinetic (PK) parameters. Preliminary efficacy analysis was performed on the response-evaluable population, including best overall response, progression-free survival (PFS), and duration of response (DOR) per investigator assessment, according to Lugano 2014 response criteria. Results: As of June 14, 2022, 44 patients were enrolled and receiving TAZ + R2 (400 [n=6], 600 [n=19], and 800 mg [n=19]). Median age was 67 years, and 31.8% of patients had received >1 prior therapy. Overall, 35/42 patients (83.3%) had wild-type (WT) EZH2 FL. Patients with high-risk disease include 15 patients (34.1%) with rituximab-refractory disease and 12 patients (27.3%) with POD24 disease. Median duration of treatment exposure of tazemetostat was 9.1 months. No dose-limiting toxicities were observed in phase 1b, and no new safety signals were identified as of the data cutoff. The PK of TAZ at all dose levels was not altered by concomitant administration of daily oral lenalidomide 20 mg, and the PK of lenalidomide was not altered by concomitant administration of any of the TAZ doses. The RP3D of TAZ was determined to be 800 mg BID in combination with R2. The most common grade 3-4 TEAE was neutropenia (n=15; 34.1%). The most frequent type of dose modification due to TEAEs for any study treatment was drug interruption (n=30; 68.2%). In the 800-mg cohort, the median dose intensity was 98%, 93%, and 100% for tazemetostat, lenalidomide, and rituximab, respectively. Of 41 patients evaluable for tumor assessment, 21 (51.2%) had a complete response, 19 (46.3%) had a partial response, and 1 (2.4%) had stable disease. The overall response rate (ORR) in the response-evaluable population was 97.6% (n=40). The ORRs in patients with WT EZH2 and MT EZH2 were 97% (n=32) and 100% (n=7), respectively. ORRs in patients with rituximab-refractory disease was 100% (n=14) and in patients with POD24 disease was 100% (n=11). With a median follow-up of 11.2 months, median PFS and median DOR were not reached and appeared to be similar, regardless of rituximab-refractory, POD24, or EZH2 mutation status. Conclusions: TAZ + R2 combination therapy demonstrates a consistent and manageable safety profile, with no new safety signals. The combination therapy maintained its efficacy, regardless of mutation status. Durable responses were seen in patients with high-risk disease, including those with rituximab-refractory and POD24 disease. The 2-arm randomized phase 3 portion will further explore the efficacy and safety of TAZ RP3D 800 mg + R2 in ≈500 patients with R/R FL who completed ≥1 prior systemic therapy.

Sintilimab Plus P-Gemox (Pegaspargase, Gemcitabine and Oxaliplatin) Regimen for Newly-Diagnosed Advanced, Extranodal Natural Killer/T Cell Lymphoma, Nasal Type: A Multicenter, Phase 2 Cohort of the Open-Label Spirit Study

Background: Extranodal Natural Killer/T Cell Lymphoma (ENKTL) is an aggressive non-Hodgkin lymphoma with a high incidence in Asian and south American populations. Pegaspargase, oxaliplatin plus gemcitabine are considered as the standard first-line therapy for advanced ENKTL, but the prognosis remains poor. In ENKTL, most patients overexpress PD-L1 protein, which is associated with a poor prognosis, and suggests that ENKTL should be sensitive to PD-1/PD-L1 axis blockade. In a phase II trial, the PD-1 mAb sintilimab showed promising efficacy as monotherapy in r/r ENKTL (Tao, Signal Transduct Target Ther, 2022). Additionally, we previously conducted a retrospective study of PD-1 mAb combined P-GEMOX for the treatment of advanced ENKTL patients (pts), which showing favorable antitumor activity with a non-overlapping toxicity profile (Cai, Signal Transduct Target Ther, 2020). Therefore, we conducted this prospective phase II trial to evaluate the efficacy and safety of sintilimab plus P-GEMOX as first-line therapy in pts with advanced ENKTL. Methods: This is a prospective, single-arm, open-label, multi-center, phase II clinical trial. Adult treatment-naive pts with histologically confirmed ENKTL nasal type had at least one measurable or evaluable lesion were enrolled to receive six cycles of sintilimab 200 mg plus pegaspargase 2000 U/m2 (day 1), gemcitabine 1g/m2 (days 1 and 8), and oxaliplatin 130 mg/m2 (day 1) (induction phase), followed by sintilimab 200 mg maintenance every 3 weeks (maintenance phase) for up to 2 years or until disease progression or unacceptable toxicities. Involved field radiotherapy (IFRT) is allowed for residual lesions after induction therapy. The primary endpoint was the proportion of pts who achieved complete response rate (CR) in response evaluable population. Secondary endpoints included overall response rate (ORR), response at the end of induction therapy (EoT), duration of response (DOR), progression-free survival (PFS), overall survival (OS), disease control rate (DCR), and safety. Treatment related adverse events (TRAE) were rated according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) 5.0. This trial is registered with ClinicalTrials.gov, number NCT04127227. Results: From November 2019 to April 2022, 27 eligible pts were enrolled. Median age was 38 years (range, 25-72), 19 (70.4%) were male, 14 (22.2%) pts had PINK-E score ≥ 3 points (Table 1). Of 24 response evaluable pts, the ORR was 100% (24/24), and the CR rate reached 87.5% (21/24, figure 1, 2). At data cut-off, 18 pts completed 6 cycles of induction therapy and entered the maintenance phase, 1 patient experienced disease progression after 4 cycles of the treatment, and the EoT CR rate of induction phase is 13/19 (68.4%). The median time to response (TTR) was 1.6 (1.4-3.8) months. During the maintenance phase, 5 more pts achieved CR and at the time of analysis, The median follow-up time was 16.7 (3.0-32.0) months. The mOS and mPFS were not reached, estimated 1-year OS rate was 100%, 1-year PFS rate was 95%.All (100%) pts experienced TRAE at any grade. The most common toxicity was neutropenia (96.3%) and the majority of TRAEs were reported during the first two cycles of the induction therapy. Grade 3-4 TRAE reported in ≥5% of pts included neutropenia (48.1%), triglycerides increased (37.0%), leukopenia (29.5%), anemia (25.9%), thrombocytopenia (25.9%), albumin decreased (7.4%), and lipase increased (7.4%). Immune-related AEs (irAEs) were reported in 16 pts, including a grade 3 hypothyroidism which led to permanent treatment discontinuation in 1 (3.7%) patient, and the remaining irAEs were all grade 1-2. All TRAEs were manageable and only 1 patient discontinued treatment due to TRAEs during maintenance phase. Conclusions: Combination of sintilimab plus P-GEMOX Regimen yielded promising clinical activity with a manageable safety profile, supporting immunochemotherapy as a new first-line treatment option for pts with advanced ENKTL. Treatment and follow-up are currently ongoing and further studies have been initiated to explore biomarkers to better predict response and long-term survival. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Subcutaneous Epcoritamab + R-Dhax/C in Patients with Relapsed or Refractory Diffuse Large B-Cell Lymphoma Eligible for Autologous Stem Cell Transplant: Updated Phase 1/2 Results

Background: For patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) who are eligible for autologous stem cell transplant (ASCT), salvage immunochemotherapy, such as rituximab, dexamethasone, cytarabine, and oxaliplatin or carboplatin (R-DHAX/C), followed by consolidation with high-dose therapy (HDT) and ASCT, is part of the standard of care. However, this treatment plan is unsuccessful in more than half of patients. Novel treatment options are needed to achieve improved responses and more favorable long-term outcomes. Epcoritamab, a subcutaneously administered bispecific antibody that targets CD3 and CD20, has demonstrated clinically meaningful antitumor activity both as a single agent (in the first-in-human phase 1/2 EPCORE NHL-1 trial; NCT03625037) and in combination with standard of care therapies (in the phase 1/2 EPCORE NHL-2 trial; NCT04663347) across B-cell non-Hodgkin lymphoma subtypes. Here we present updated results from arm 4 (epcoritamab + R-DHAX/C) of the EPCORE NHL-2 trial, which is the first clinical study of a bispecific antibody in combination with salvage immunochemotherapy in this high-risk, refractory, ASCT-eligible population. Methods: Adults with R/R CD20+ DLBCL who were eligible for HDT-ASCT were treated with standard R-DHAX/C and subcutaneous epcoritamab (21-d cycles: QW, cycles 1-3). If HDT-ASCT was deferred, patients could continue epcoritamab monotherapy (21-d cycle: QW, cycle 4; 28-d cycles: Q2W, cycles 5-9, and Q4W, cycles ≥10) until disease progression or unacceptable toxicity. Corticosteroid premedication and step-up epcoritamab dosing were required in cycle 1 to mitigate CRS. Response was determined by PET-CT using Lugano 2014 criteria. Results: As of the data cutoff on June 10, 2022, 29 patients had received epcoritamab + R-DHAX/C. The median age was 58 y (range, 28-75), 72% of patients had received 1 prior line of therapy, 28% had received 2 or 3 prior therapies, 34% had transformed disease, 66% had primary refractory disease, and 59% were refractory to their last line of therapy. Three patients had prior CAR T-cell therapy. The median duration of follow-up was 9.2 mo (range, 1.7-14.2). The most common treatment-emergent AEs (TEAEs) of any grade were thrombocytopenia (69%), anemia (45%), CRS (41%), neutropenia (41%), nausea (34%), and fatigue (28%). All CRS events were low grade (grade 1 in 31% of patients, grade 2 in 10% of patients) and resolved, with a median time to resolution of 2 d (range, 1-8). Most CRS events occurred after the first full dose. One patient experienced a grade 2 ICANS event, which resolved but led to treatment discontinuation. No clinical tumor lysis syndrome was observed, and no fatal TEAEs were reported. Of the 26 response-evaluable patients (Figure), 15 (58%) proceeded to transplant per protocol; for these 15 patients, the overall response rate (ORR) with the combination of epcoritamab + R-DHAX/C was 100% (15/15), with 80% (12/15) achieving a complete metabolic response (CMR) and 20% (3/15) achieving a partial metabolic response (PMR). Patients continuing epcoritamab monotherapy instead of HDT-ASCT had an ORR of 64% (7/11), with 45% (5/11) achieving a CMR and 18% (2/11) achieving a PMR. The primary reason for a patient not proceeding to HDT-ASCT was patient choice. Median duration of response was not reached among the 7 responders continuing epcoritamab monotherapy. In the response-evaluable population overall, the ORR was 85% (22/26); rates of CMR and PMR were 65% (17/26) and 19% (5/26), respectively. Conclusions: Subcutaneous epcoritamab in combination with R-DHAX/C demonstrated a manageable safety profile in ASCT-eligible patients with R/R DLBCL. Importantly, no new safety findings were observed. ICANS was rare, and all CRS events were low grade and resolved. High ORRs and CMR rates were observed. As of the data cutoff date, most patients had proceeded to ASCT or remained on epcoritamab in CMR. In conclusion, epcoritamab is well suited for salvage combination therapy. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Updated interim analysis of the randomized phase 1b/3 study of tazemetostat in combination with lenalidomide and rituximab in patients with relapsed/refractory follicular lymphoma.

7572 Background: Tazemetostat (TAZ), an enhancer of zeste homolog 2 (EZH2) inhibitor, showed antitumor activity as monotherapy in patients with relapsed or refractory (R/R) follicular lymphoma (FL) who received ≥2 prior lines of therapy. In clinical studies in patients with R/R FL, lenalidomide and rituximab (R2) demonstrated an objective response rate (ORR) of 73%–78% and median progression-free survival (PFS) of 36–39 months. This global, multicenter phase 1b/3 study is designed to determine the recommended phase 3 dose (RP3D), efficacy, and safety of TAZ + R2 in patients with R/R FL after ≥1 prior therapy. We report an updated interim analysis of the phase 1b safety run-in where we assess the clinical activity and pharmacokinetics (PK) of TAZ when administered with R2 in patients with R/R FL. Methods: Phase 1b evaluated TAZ at 3 dose levels (400, 600, and 800 mg orally twice daily) in 28-day cycles with standard-dose R2 (NCT04224493). In addition to PK and safety, preliminary efficacy analysis was performed on the response-evaluable population, including best overall response, PFS, and duration of response (DOR) per investigator assessment according to Lugano 2014 response criteria. Results: As of January 22, 2022, 43 patients were enrolled and receiving TAZ + R2 (400 [n = 4], 600 [n = 18], and 800 mg [n = 21]). These patients had a median age of 67 years (range, 39–83) and received a median of 1 prior therapy (range, 1–4). Overall, 15/43 (34.9%) patients were refractory to rituximab, 10/39 (25.6%) had POD24, and 6/41 (14.6%) had mutant-type EZH2. Median duration of treatment exposure was 32.0 weeks (range, 4.1–68.1). Mean Cmax and AUC0–t of TAZ 800 mg + R2 at steady state were similar to those found for TAZ as monotherapy. PK of TAZ was not altered by concomitant administration of daily oral lenalidomide 20 mg, and PK of lenalidomide was not altered by concomitant administration of TAZ. No dose-limiting toxicities were observed in phase 1b, and no new safety signals were identified as of the January 2022 data cutoff. Serious treatment-emergent adverse events (TEAEs) were observed in 14 (32.6%) patients. Grade 3–4 TEAEs were observed in 24 (55.8%) patients; the most common grade 3–4 TEAE was neutrophil count decrease (n = 13; 30.2%). Of 38 patients evaluable for tumor assessment, 19 (50.0%) had a complete response, 17 (44.7%) had a partial response, and 2 (5.3%) had stable disease. ORR was 94.7% (n = 36). With a median follow-up of 5.8 months, median PFS and DOR were not reached and appeared to be similar, regardless of mutation status. Conclusions: TAZ + R2 combination demonstrates consistent and unaltered PK for TAZ and lenalidomide as well as a favorable safety profile and efficacy trend. The 2-arm randomized phase 3 portion will further explore the efficacy and safety of TAZ RP3D 800 mg + R2 in ≈500 patients with R/R FL. Clinical trial information: NCT04224493.

Crizotinib in ROS1-rearranged lung cancer (EUCROSS): Updated overall survival.

9078 Background: ROS1 rearrangements are found in approximately 1% of non-small cell lung cancer (NSCLC) patients. Prospective clinical trials showed high efficacy of crizotinib in this molecular subset. Lately, we reported an overall response rate (ORR) of 70% and a median progression-free survival (PFS) of 19.4 months for patients treated within the EUCROSS trial (Michels et al. Clin Oncol, 37(15_suppl):9066-9066, 2019). Here we present an updated analysis of the overall survival. Methods: EUCROSS is a European multi-centre, single arm phase 2 trial (Clinicaltrial.gov identifier: NCT02183870). Key eligibility criteria were ≥18 years of age, advanced/metastatic lung cancer, centrally confirmed ROS1-rearranged (fluorescence-in situ hybridisation) and no or stable brain metastases at baseline. Crizotinib was given at a dose of 250 mg twice daily. Primary endpoint of the trial was investigator-assessed ORR in the response-evaluable population (Response Evaluation Criteria in Solid Tumors, version 1.1), with secondary endpoints of PFS and overall survival (OS). Results: Of the 34 patients who received at least one dose of crizotinib (intention-to-treat population, ITT), 30 were included the primary efficacy analysis set (PAS). After a median follow-up of 55.9 months, 13 (43%) patients in the PAS and 15 (44%) in the ITT had died. Median OS was not reached in either group (95% CI, 17.1-NR and 20.3-NR, respectively). OS was negatively correlated with the presence of brain metastases (Log-rank p = 0.1805) and TP53 mutations (Log-rank p = 0.015). Detailed listings of the survival rates are depicted in Table. No new safety signals were observed. Owing to the approval of crizotinib by the European Medicines Agency, all patients who were still on treatment by January 24th 2018 (n=8), were prescribed crizotinib outside the trial. Conclusions: Updated OS highlights the efficacy of crizotinib in patients with ROS1-rearranged lung cancer. Patients with co-occurring TP53 mutations or brain metastases had worse outcomes and represent challenging populations. Clinical trial information: NCT02183870. [Table: see text]

Olutasidenib (FT-2102) in patients with relapsed or refractory IDH1-mutant glioma: A multicenter, open-label, phase Ib/II trial.

Olutasidenib (FT-2102) is a highly potent, orally bioavailable, brain-penetrant and selective inhibitor of mutant isocitrate dehydrogenase 1 (IDH1). The aim of the study was to determine the safety and clinical activity of olutasidenib in patients with relapsed/refractory gliomas harboring an IDH1R132X mutation. This was an open-label, multicenter, nonrandomized, phase Ib/II clinical trial. Eligible patients (≥18 years) had histologically confirmed IDH1R132X-mutated glioma that relapsed or progressed on or following standard therapy and had measurable disease. Patients received olutasidenib, 150 mg orally twice daily (BID) in continuous 28-day cycles. The primary endpoints were dose-limiting toxicities (DLTs) (cycle 1) and safety in phase I and objective response rate using the Modified Response Assessment in Neuro-Oncology criteria in phase II. Twenty-six patients were enrolled and followed for a median 15.1 months (7.3‒19.4). No DLTs were observed in the single-agent glioma cohort and the pharmacokinetic relationship supported olutasidenib 150 mg BID as the recommended phase II dose. In the response-evaluable population, disease control rate (objective response plus stable disease) was 48%. Two (8%) patients demonstrated a best response of partial response and eight (32%) had stable disease for at least 4 months. Grade 3‒4 adverse events (≥10%) included alanine aminotransferase increased and aspartate aminotransferase increased (three [12%], each). Olutasidenib 150 mg BID was well tolerated in patients with relapsed/refractory gliomas harboring an IDH1R132X mutation and demonstrated preliminary evidence of clinical activity in this heavily pretreated population.

Abstract P1-17-11: Updated data from AMEERA-1: Phase 1/2 study of amcenestrant (SAR439859), an oral selective estrogen receptor (ER) degrader (SERD), combined with palbociclib in postmenopausal women with ER+/HER2- advanced breast cancer

Abstract Background: In Arm 2 of the ongoing AMEERA-1 trial (NCT03284957), amcenestrant, an optimized oral SERD combined with the CDK4/6 inhibitor (CDK4/6i) palbociclib demonstrated favorable safety and encouraging antitumor activity among patients with endocrine-resistant ER+/HER2− advanced breast cancer in dose escalation (Part C) and dose expansion (Part D) (Chandarlapaty et al., ASCO 2021; abstract 1058). Here we report an update of safety, antitumor activity data, and progression-free survival (PFS), of amcenestrant 200 mg in combination with palbociclib. Analysis of genomic data, including modulation over time and correlation with clinical outcome, will also be presented. Methods: The trial enrolled postmenopausal women with ER+/HER2- locally-advanced or metastatic breast cancer with disease progression while on ≥ 6 months of prior endocrine therapy (ET) in the advanced setting, or who relapsed on adjuvant ET after the first 2 years of treatment or within 12 months of completing adjuvant ET. Prior chemotherapy (≤ 1) was allowed as well as prior CDK4/6i-based therapy (≤ 1, in Part C only). In this pooled analysis (N = 39), patients in Parts C + D received amcenestrant 200 mg once daily + palbociclib 125 mg (21 days on/7 days off), administered in 28-day cycles. Safety in the pooled analysis was reported using methods previously described (Chandarlapaty et al., ASCO 2021; abstract 1058). Data from investigator-assessed, response-evaluable patients in the pooled analysis without prior exposure to targeted therapies (N = 34) were used to evaluate antitumor activity per RECIST v1.1, including the objective response rate (ORR), clinical benefit rate (CBR), and PFS. Results: At a data cutoff of May 30, 2021, in the pooled analysis (N = 39), the median (range) duration of treatment exposure was 44.3 weeks (1-80). Of 39 patients, 24 (61.5%) had initiated at least 10 cycles (40 weeks) of treatment, with 20/39 (51.3%) still receiving ongoing treatment. Among the 34/39 (87.2%) patients in the response-evaluable population, median follow-up was 48.3 weeks with a PFS probability of being event free at 24 weeks of 78.2% (95% CI: 59.6%; 89.0%). Median PFS is not yet mature, with 14/34 (41.2%) patients having had a PFS event (all were progression events and no deaths occurred). The ORR was 11/34 (32.4%; all partial responses). Clinical benefit at 24 weeks was seen in 25/34 (CBR = 73.5%) patients. Median (range) time to first response was 16.3 weeks (8-32). Amcenestrant treatment-related adverse events (TRAEs) and palbociclib TRAEs, respectively, occurred in 27/39 (69.2%) and 35/39 (89.7%) patients for all grade events and in 5/39 (12.8%) and 18/39 (46.2%) patients for Grade ≥ 3 events. Non-hematological amcenestrant and palbociclib TRAEs are reported in Table 1. Neutrophil count decrease based on hematological laboratory abnormalities was observed in the majority of patients (94.9%; with Grade ≥ 3 in 56.4%). Conclusions: Among postmenopausal women with endocrine-resistant ER+/HER2- advanced breast cancer, amcenestrant 200 mg in combination with the approved dose of palbociclib continues to demonstrate encouraging long-term antitumor activity, sustained clinical benefit, and a favorable safety profile consistent with previous results. Funding: Sanofi. Table 1.Non-hematological amcenestrant and palbociclib TRAEs occurring in &amp;gt; 10% of patientsPooled Analysis. Amcenestrant 200 mg + Palbociclib. (Parts C + D; N = 39)Amcenestrant Non-hematological TRAEs, n (%)All GradesGrade ≥ 3–Fatigue7 (17.9)0–Nausea7 (17.9)0–Arthralgia4 (10.3)0–Asthenia4 (10.3)0–Hot flush4 (10.3)0Palbociclib Non-hematological TRAEs, n (%)All GradesGrade ≥ 3–Fatigue12 (30.8)0–Nausea10 (25.6)0–Asthenia4 (10.3)0–Dysgeusia4 (10.3)0–Stomatitis4 (10.3)0 Citation Format: Sarat Chandarlapaty, Hannah M Linden, Patrick Neven, Katarina Petrakova, Aditya Bardia, Peter Kabos, Sofia Braga, Valentina Boni, Alice Gosselin, Marina Celanovic, Patrick Cohen, Gautier Paux, Vasiliki Pelekanou, Nils Ternès, Joon Sang Lee, Mario Campone. Updated data from AMEERA-1: Phase 1/2 study of amcenestrant (SAR439859), an oral selective estrogen receptor (ER) degrader (SERD), combined with palbociclib in postmenopausal women with ER+/HER2- advanced breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-17-11.

Daratumumab (DARA) Plus Lenalidomide, Bortezomib, and Dexamethasone (RVd) in Patients (Pts) with Transplant-Eligible Newly Diagnosed Multiple Myeloma (NDMM): Updated Analysis of Griffin after 24 Months of Maintenance

Daratumumab (DARA) Plus Lenalidomide, Bortezomib, and Dexamethasone (RVd) in Patients (Pts) with Transplant-Eligible Newly Diagnosed Multiple Myeloma (NDMM): Updated Analysis of Griffin after 24 Months of Maintenance

AdoRN Trial: Atezolizumab in combination with neoadjuvant chemotherapy and interval cytoreductive surgery for patients with newly-diagnosed advanced-stage epithelial ovarian cancer

<h3>Objectives:</h3> To determine safety, efficacy, and biomarkers of response to neoadjuvant therapy (NACT) with atezolizumab (atezo), weekly paclitaxel and carboplatin (wPC) followed by maintenance (maint) atezo±bevacizumab (bev) in women with advanced epithelial ovarian, tubal, and peritoneal cancer (EOC). <h3>Methods:</h3> Patients (pts) with high-grade EOC were eligible. Pts underwent pretreatment biopsy, received paclitaxel 80 mg/m² IV D1/8/15 + carboplatin AUC6 IV D1 + atezo 1200 mg D1 every 3 weeks x 3 cycles followed by interval cytoreductive surgery (ICS). Post-surgery, pts received adjuvant atezo, wPC±bev followed by maint atezo±bev. Primary objective was to assess safety of the combination when given prior to ICS. Early stopping rules were built around the primary safety endpoint if patients were unable to proceed to planned ICS within the specified timeframe (≤6 weeks from last dose of NACT) due to atezo-related toxicities. Safety was assessed in all treated pts using frequency and severity of adverse events (AE). Objective response rate (ORR), pathologic complete response rate (pCR) at ICS, and progression free survival (PFS) were determined. Planned exploratory objectives included quantitation of changes in PD-L1 expression, tumor-infiltrating lymphocyte subpopulations, immune checkpoint receptor profile, and immune blood-based markers. <h3>Results:</h3> A total of 18 pts enrolled and received therapy between 05/15/2018 - 07/14/2020. Median age was 69 years (range 46-87). Key disease characteristics: 18 (100%) pts had high-grade serous EOC; 13 (72%) pts had Stage III and 5 (28%) had stage IV disease; <i>BRCA</i> status: 5 (28%) mutations, 13 (72%) wildtype. Grade (G) 3/4 atezo-related AEs included 1 (6%) G3 anemia, 2 (11%) G3 thrombocytopenia, 2 (11%) G4 hypokalemia, 2 (11%) G3 rash, 1 (6%) thrombotic event. Other AEs of special interest included pneumonitis (n=3, 2 G2, 1 G1), blurred vision (n=1, G1), and myositis (n=1, G1). A total of 3 pts withdrew prior to ICS; 1 to change to every 3 weeks therapy locally, 1 due to non-atezo related AEs, and 1 due to negative results of IMAGYN050. These 3 pts are not included in the response-evaluable population (n=15). Nine (60%) pts had a partial response (PR) after 3 cycles and 6 (40%) had stable disease. All 15 pts underwent ICS; 1 had delayed cytoreduction due to pulmonary embolism, possibly atezo-related. Cytoreduction status was optimal in 86% pts [R0 8 (53%), R1 (33%)], and suboptimal in 2 (13%) pts; no pCRs were observed. All response-evaluable pts completed chemotherapy. Pts opted for maint therapy as follows: 6 (40%) adjuvant/maint atezo+bev; 4 (27%) atezo alone; and 5 (33%) withdrew for PARP inhibitor maint. A total of 2 (20%) of 10 receiving atezo maint discontinued due to recurrence. Blood-based and tumor biomarker results will be presented. <h3>Conclusions:</h3> NACT with atezo + wPC followed by maint atezo±bev was feasible with no new safety signals. Biomarker analysis is ongoing to identify potential candidates who may benefit from atezo front-line therapy.

Daratumumab in Combination with Carfilzomib and Dexamethasone in Patients (pts) with Relapsed Multiple Myeloma (MMY1001): An Open-Label, Phase 1b Study

Daratumumab in Combination with Carfilzomib and Dexamethasone in Patients (pts) with Relapsed Multiple Myeloma (MMY1001): An Open-Label, Phase 1b Study

Final results of a phase 1b study of isatuximab short-duration fixed-volume infusion combination therapy for relapsed/refractory multiple myeloma

Part B of this phase 1b study (ClinicalTrials.gov number, NCT02283775) evaluated safety and efficacy of a fixed-volume infusion of isatuximab, an anti-CD38 monoclonal antibody, in combination with pomalidomide and dexamethasone (Pd) in relapsed/refractory multiple myeloma patients. Isatuximab (10 mg/kg weekly for 4 weeks, then every other week) was administered as a fixed-volume infusion of 250 mL (mL/h infusion rate) with standard doses of Pd on 28-day cycles. Patients (N = 47) had a median of three prior treatment lines (range, 1–8). Median duration of exposure was 36.9 weeks and median duration of first, second, and 3+ infusions were 3.7, 1.8, and 1.2 h, respectively. The most common non-hematologic treatment-emergent adverse events were fatigue (63.8%), infusion reactions (IRs), cough, and upper respiratory tract infection (40.4% each). IRs were all grade 2 and occurred only during the first infusion. The overall response rate was 53.2% in all patients (55.5% in response-evaluable population, 60.0% in daratumumab-naïve patients). Efficacy and safety findings were consistent with data from the isatuximab plus Pd infusion schedule in Part A of this study and also from the phase 3 ICARIA-MM study, and these new data confirm the safety, efficacy, and feasibility of fixed-volume infusion of isatuximab.

LocoMMotion: A prospective, non-interventional, multinational study of real-life current standards of care in patients with relapsed/refractory multiple myeloma (RRMM) receiving ≥3 prior lines of therapy.

8041 Background: Multiple myeloma (MM) remains incurable despite advances in medical treatment that have improved survival. Even with these improvements, most patients with MM eventually progress through standard drug classes of proteasome inhibitors (PIs), immunomodulatory drugs (IMiDs), anti-CD38 monoclonal antibodies (mAbs), and others. There are currently no prospective data on real-world standard-of-care (SOC) in patients who progress after PIs, IMiDs, and anti-CD38 mAbs. Here, we present interim results from LocoMMotion (NCT04035226), the first prospective efficacy and safety study of real-life SOC in patients with RRMM. Methods: Eligible patients (aged ≥18 years [y]) with a diagnosis of MM were enrolled between August 2019 and October 2020 from 75 sites across 9 European countries and the US. Patients were included if they received ≥3 prior lines of therapy or were double-refractory to a PI and IMiD, had measurable disease at screening, received at least a PI, an IMiD, and anti-CD38 mAb with documented progressive disease since their last line of therapy, and had an ECOG PS score of 0 or 1. Responses were assessed per International Myeloma Working Group response criteria. A Response Review Committee assessed the overall response rate (ORR, primary objective) of real-life current SOC. Secondary objectives of the study included additional efficacy and safety evaluation of real-life SOC. Results: The data cut-off was November 4, 2020 for the first interim analysis of 225 patients with a median follow-up of 3.7 months (range: 0–12.7), 22 (9.8%) patients were from the US and 203 (90.2%) were from Europe. Median age was 68 y (range: 41–89), 124 (55.1%) were male, 162 (72.0%) had a baseline ECOG PS score of 1, and median time since initial MM diagnosis was 6.0 y (range: 0.3–22.8). Patients had received a median of 4.0 (range: 2–13) prior lines of therapy; all patients were triple-class exposed, 166 (73.8%) were triple-class refractory, and 208 (92.4%) were refractory to last line of therapy. The ORR with real-life SOC salvage therapy was 20.1% (95% CI: 15.0–26.0) in the response-evaluable population (n = 219). Treatment-emergent adverse events (TEAEs) were reported in 148 (65.8%) patients, 95 (42.2%) were grade ≥3. The most common grade ≥3 TEAEs were anemia, thrombocytopenia, and neutropenia. Fifteen deaths (6.7%) occurred due to TEAEs during the study. Treatment is ongoing in 121 (53.8%) patients. Conclusions: The interim results of this first, prospective study of real-life SOC treatment in heavily pretreated, triple-class exposed patients with RRMM demonstrate that patients continue to progress after multiple lines of therapy and have poor outcomes. Therefore, there is a need for new treatments with novel mechanisms of action for this patient population. Clinical trial information: NCT04035226.

Abstract PD8-08: A phase 1/2 study of SAR439859, an oral selective estrogen receptor (ER) degrader (SERD), as monotherapy and in combination with other anti-cancer therapies in postmenopausal women with ER-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (mBC): AMEERA-1

Abstract Background SERDs belong to a class of ER-targeted therapies that antagonize and degrade ERs, including in ER-dependent tumors resistant to other endocrine therapies (ET). This study (AMEERA-1; NCT03284957) investigates SAR439859, an oral SERD, as monotherapy and (in ongoing cohorts) in combination with targeted therapies in patients (pts) with ER+/HER2- mBC. Here we report updated safety and antitumor activity with SAR439859 monotherapy, including exploratory analyses by prior therapy and ESR1 status. Methods This open-label, phase 1/2, first-in-human study assessed SAR439859 as monotherapy in Parts A (dose escalation 20-600 mg once daily [QD]) and B (dose expansion with recommended dose at 400 mg QD). Eligible pts were heavily pre-treated, postmenopausal women with ER+/HER2- mBC and measurable disease who received ≥6 months of prior ET in the advanced setting. Prior chemotherapy, mammalian target of rapamycin inhibitors (mTORi) and cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) for advanced disease were allowed. This analysis pooled data from pts receiving SAR439859 ≥150 mg (Part A) and 400 mg (Part B), administered in 28-day cycles. Antitumor activity was assessed by the objective response rate and clinical benefit rate (CBR: complete response [CR], partial response [PR] and stable disease [SD] ≥24 weeks) per RECIST v1.1, determined by investigators. Analyses by prior therapy and baseline ESR1 mutation status were performed. Safety was also evaluated. Results Pts (n = 62; Part A: 13; Part B: 49) had a median age of 63 (range 37-88) years and ECOG PS 0 (59.7%) or 1 (40.3%); 93.5% had visceral metastases. Pts had a median of 2 (range 1-8) prior lines of therapy in the advanced setting (48.4% had ≥3 prior lines): all had prior ET and 72.6% had prior targeted therapy. SAR439859 monotherapy showed antitumor activity in the response-evaluable population (n = 59) and in subset populations with ≤3 prior lines (n = 33) or without prior mTORi, CDK4/6i, or SERD (n = 14) (Table 1). For pts with ESR1 status (n = 58), CBR with SAR439859 was comparable in ESR1 wild-type (36.7%) and mutant mBC (32.1%), with similar results in subpopulations. Treatment-related adverse events (TRAEs) occurred in 62.9% of pts (all grade 1-2); none resulted in SAR439859 discontinuation. Most frequent TRAEs were hot flush (16.1%); constipation and arthralgia (each 9.7%); decreased appetite, vomiting, diarrhea and nausea (each 8.1%); and fatigue (6.5%). Conclusions Among heavily pre-treated pts, SAR439859 demonstrated antitumor activity, similar to historical single-agent fulvestrant activity in less heavily pre-treated pts with advanced/mBC (2L+ setting; no prior targeted agents) (indirect comparison). In both subsets of pts with fewer prior advanced lines of therapy, SAR439859 showed trends of greater clinical activity versus historical fulvestrant activity. SAR439859 had a favorable safety profile with limited TRAEs. No safety signals of cardiac or ocular toxicities were observed. Ongoing parts of the study are investigating SAR439859 in combination with targeted therapies. Based on the monotherapy results, a randomized phase 2 study is investigating SAR439859 compared with physician’s choice in a 2L+ setting (AMEERA-3; NCT04059484). Funding: Sanofi. Antitumor activity overall and in subpopulations by prior lines of therapy (Parts A+B)Overall population (A+B)≤3 Prior advanced linesWithout prior targeted therapy(n = 59)a(n = 33)b(n = 14)cBOR, n (%)–CR000–PR5 (8.5)5 (15.2)3 (21.4)–SD24 (40.7)15 (45.5)8 (57.1)–PD30 (50.8)13 (39.4)3 (21.4)ORR, n (%)5 (8.5)5 (15.2)3 (21.4)CBR, n (%)20 (33.9)14 (42.4)9 (64.3)aPooled cohort (A ≥150 mg QD + B);bSubset of pooled cohort with ≤3 prior lines in the metastatic setting, including ≤1 of either prior chemotherapy or CDK4/6i and no prior mTORi; cSubset of pooled cohort with no prior mTORi, CDK4/6i, or fulvestrant.BOR, best overall response; CBR, clinical benefit rate; CR, complete response; ORR, objective response rate; PD, progressive disease; PR, partial response; SD, stable disease. Citation Format: Hannah M Linden, Mario Campone, Aditya Bardia, Gary A Ulaner, Alice Gosselin, Séverine Doroumian, Vasiliki Pelekanou, Marina Celanovic, Sarat Chandarlapaty. A phase 1/2 study of SAR439859, an oral selective estrogen receptor (ER) degrader (SERD), as monotherapy and in combination with other anti-cancer therapies in postmenopausal women with ER-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (mBC): AMEERA-1 [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PD8-08.

Nivolumab versus chemotherapy in Japanese patients with advanced esophageal squamous cell carcinoma: a subgroup analysis of a multicenter, randomized, open-label, phase 3 trial (ATTRACTION-3)

BackgroundThe efficacy and safety of nivolumab versus chemotherapy was evaluated in the Japanese subpopulation from the overall intent-to-treat (ITT) population of the ATTRACTION-3 trial conducted in patients with advanced esophageal squamous cell carcinoma (ESCC) as second-line treatment.MethodsData from Japanese patients enrolled in the multicenter, randomized, open-label, phase 3 ATTRACTION-3 trial were analyzed. The primary endpoint was overall survival (OS). Secondary endpoints included duration of response (DOR), objective response rate (ORR), disease control rate (DCR), and safety. Exploratory subgroup analyses evaluated the association between OS and stratification factors/baseline variables.ResultsOverall, 274 (nivolumab, 136; chemotherapy, 138) of the 419 patients in ATTRACTION-3 were enrolled from Japan: response-evaluable population (107; 108) and safety population (135; 138). OS tended to be longer in the nivolumab group versus the chemotherapy group (median: 13.4 months vs. 9.4 months; HR, 0.77; 95% CI 0.59–1.01). Median DOR was longer in the nivolumab group (7.6 months) versus the chemotherapy group (3.6 months). ORRs were similar between the nivolumab [22.4% of patients (24/107)] and chemotherapy groups [22.2% (24/108); odds ratio, 0.98; 95% CI 0.52–1.87]. DCR was lower in the nivolumab group [41.1% (44/107)] versus the chemotherapy group [66.7% (72/108)]. OS in the exploratory analysis consistently favored the nivolumab group versus the chemotherapy group. Overall, nivolumab demonstrated favorable efficacy and safety versus chemotherapy in the Japanese subpopulation, and the trend was similar to that observed in the overall ATTRACTION-3 ITT population.ConclusionNivolumab represents a new standard second-line treatment option for Japanese patients with advanced ESCC.

Daratumumab (DARA) Plus Lenalidomide, Bortezomib, and Dexamethasone (RVd) in Patients with Transplant-Eligible Newly Diagnosed Multiple Myeloma (NDMM): Updated Analysis of Griffin after 12 Months of Maintenance Therapy

Daratumumab (DARA) Plus Lenalidomide, Bortezomib, and Dexamethasone (RVd) in Patients with Transplant-Eligible Newly Diagnosed Multiple Myeloma (NDMM): Updated Analysis of Griffin after 12 Months of Maintenance Therapy