Cycles Q3w Research Articles

Abstract PO1-29-03: Efficacy, Safety, and Immunogenicity of TQ-B211 (a Trastuzumab Biosimilar) Plus Docetaxel versus Herceptin® Plus Docetaxel for HER2-positive Metastatic Breast Cancer: a Double-blind, Randomised, Multicenter, Phase 3 Trial

Abstract Background: Breast cancer is one of the most common malignant tumors in women worldwide. In China, the incidence of breast cancer has been steadily increasing. Approximately 30% of human breast cancers exhibit human epidermal growth factor receptor 2 (HER2) positivity, which is closely associated with tumor aggressiveness, high recurrence rate and high mortality. This study aimed to evaluate the efficacy, safety, and immunogenicity of TQ-B211 (a trastuzumab biosimilar) compared to the reference trastuzumab in combination with docetaxel as first-line treatment for patients with HER2-positive metastatic breast cancer. Methods: This randomized, multicenter, double-blind phase III equivalence study enrolled HER2+ metastatic breast cancer patients aged 18-75, ECOG PS ≤1, no prior systemic chemotherapy, biologic, or targeted therapy for recurrent or metastatic disease, and at least one measurable lesion (RECIST 1.1). The patients were randomly assigned to two groups: the experimental group received TQ-B211 (8 mg/kg iv on day 1, cycle 1, followed by 6 mg/kg q3w for cycles 2-8) in combination with docetaxel (75 mg/m2 on day 2, cycle1, followed by 75 mg/m2 on day 1 for cycles 2-8), while the control group received Herceptin® in combination with docetaxel. For subjects who completed 8 cycles of treatment without disease progression and demonstrated tolerability, they were subsequently administered TQ-B211 as monotherapy until disease progression or unsuitable for further treatment. The primary efficacy endpoint was ORR up to week 24 (ORR24w). Equivalence was declared if the 90% confidence interval (CI) of relative ratio (RR) value was within the range of 0.8 to 1.25. Secondary efficacy endpoints included duration of response (DoR); progression-free survival (PFS); disease control rate (DCR); overall survival (OS), safety and immunogenicity. Results: Between December 6, 2018 and July 31, 2021, a total of 386 patients (pts) were enrolled (192 pts in the TQ-B211 group and 194 pts in the Herceptin® group). In the intention-to-treat (ITT) population, the ORR24w of the TQ-B211 group was 67.19% (95% CI: 60.55, 73.83), while the ORR24w of the Herceptin® group was 65.98% (95% CI: 59.31, 72.65). The RR of the confirmed ORR24w between the two groups was 1.02 (90%CI, 0.90, 1.15), which fell entirely in the predefined equivalence margins (0.8, 1.25), indicating comparable efficacy of the two drugs. In the ITT population, the DCR of the TQ-B211 group and the Herceptin® group were 83.85% (78.65, 89.06) and 78.35% (72.56, 84.15) respectively, with no statistically significant difference between the two groups (P=0.1940). By the data cutoff date of October 31, 2021, the median PFS was not statistically different (P=0.6834); the median OS was not reached in both groups (P=0.9246). Additionally, the data results of the per-protocol (PP) population were similar to those of the ITT population. In total, similar rates of treatment-related grade ≥3 adverse events (41.05% vs. 46.39%) occurred in the TQ-B211 and Herceptin® groups, respectively. The incidence and magnitude of immunogenicity were low in both of the two groups (ADA: 0.53% vs. 0%, Nab: both negative). Conclusion: Equivalence for efficacy was demonstrated between TQ-B211 and Herceptin® on the basis of ORR24w. Safety and immunogenicity were comparable. Citation Format: Xichun Hu, Qingyuan Zhang, Shusen Wang, Tao Sun, Xiaohua Zeng, Weimin Xie, Zhongsheng Tong, Hui Cao, Huihua Xiong, Xiuwen Wang, Jin Yang, Shuqun Zhang, Ying Wang, Chunhong Hu, Kaijian Lei, Binlin Ma, Wei Liu, Zhiyong Yu, PeiJian Peng, Hongwei Yang, Zhijun Yuan, Xiaojia Wang, Xujuan Wang, Hong Wang, Yongqian Shu, Nanlin Li, Wenbin Yue, Jingfen Wang, Daqing Wang, Zhiguo Luo, Junyang Mo, Yarong Li, Lili Sheng. Efficacy, Safety, and Immunogenicity of TQ-B211 (a Trastuzumab Biosimilar) Plus Docetaxel versus Herceptin® Plus Docetaxel for HER2-positive Metastatic Breast Cancer: a Double-blind, Randomised, Multicenter, Phase 3 Trial [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-29-03.

A Phase 1b Open-Label Study of Loncastuximab Tesirine in Combination with Other Anticancer Agents in Patients with Relapsed or Refractory (R/R) B-Cell Non-Hodgkin Lymphoma (LOTIS-7)

Background: Patients (pts) with relapsed/refractory (R/R) B-cell non-Hodgkin lymphoma (B-NHL) may not respond well to single-agent therapy. Combining agents with different mechanisms of action may enhance the efficacy of single agents. Loncastuximab tesirine (loncastuximab tesirine-lpyl; Lonca) is an FDA-approved CD19-directed antibody-drug conjugate (ADC) indicated for R/R large B-cell lymphoma and showed significant antitumor activity and manageable toxicity in a phase 2 trial in pts with R/R diffuse large B-cell lymphoma (Lancet Oncol 2021;22(6):790-800). In preclinical xenograft models, Lonca in combination with gemcitabine, polatuzumab vedotin (Pola), or phosphatidylinositol 3-kinase inhibitors showed improved antitumor activity. The safety and activity of Lonca in combination with other established anticancer agents in pts with R/R B-NHL will be evaluated in LOTIS-7. Methods: LOTIS-7 is a phase 1b, open-label, multicenter, multiarm study (NCT04970901) with 2 parts: dose escalation (part 1) and dose expansion (part 2). Approximately 200 pts with B-NHL will be enrolled (part 1, 70 pts; part 2, 130 pts). Part 2 may include DLBCL, high-grade B-cell lymphoma, follicular lymphoma, mantle cell lymphoma, marginal zone lymphoma, and Burkitt lymphoma cohorts. The design of part 2, such as the sample size, population, etc., may be informed by data collected in part 1. For safety, tolerability, and identifying the maximum tolerated dose and/or recommended dose for part 2, primary endpoints are frequency and severity of adverse events (AE), serious adverse events, dose-limiting toxicities during cycle 1, and frequency of dose modifications due to AE. For efficacy, pharmacokinetics, and immunogenicity, secondary endpoints are overall response rate, duration of response, complete response rate, progression-free survival, relapse-free survival, overall survival, Lonca concentrations, and antidrug antibodies to Lonca titers. Multiple arms are planned; currently, enrollment is open to 1 arm, wherein patients will be treated with Lonca + Pola as an outpatient infusion every 3 weeks (Q3W). In part 1, patients will receive Lonca at escalating doses (from 90 µg/kg to 150 µg/kg) and Pola at a dose of 1.8 mg/kg on day 1 of each 3-week cycle. In part 2, patients will receive Lonca in combination with Pola at the maximum tolerated dose and/or recommended dose for expansion if favorable results in part 1 are achieved. The study has a screening period (≤28 days from the day of the first dose), a treatment (Tx) period (cycles Q3W, ≤1 year), and a follow-up period (~Q12W visits, ≤2 years after Tx discontinuation). Treatment may continue for up to 1 year or until disease progression, unacceptable toxicity, or other discontinuation criteria-whichever occurs first. Key inclusion criteria are patients age ≥18 years with a pathologic diagnosis of R/R B-NHL (2016 WHO classification) and the following: those who failed/are intolerant to any approved Tx, received ≥2 systemic Tx regimens, need systemic Tx, have an ECOG performance status of 0-2, and have measurable disease (2014 Lugano Classification). Patients who previously received any study drugs; received a stem-cell transplant within 60 days prior to the start of study drugs; have lymphoma with active CNS involvement, serious skin-related disease, ascites, edema, or effusion; and have significant medical comorbidities are excluded. Results: The study opened in December 2021, and the first patient was dosed in the Lonca + Pola arm in June 2022. Funding: ADC Therapeutics SA; medical writing: CiTRUS Health Group.

P926: DARATUMUMAB, BORTEZOMIB AND DEXAMETHASONE FOR TREATMENT OF PATIENTS WITH RELAPSED OR REFRACTORY MULTIPLE MYELOMA AND SEVERE RENAL IMPAIRMENT: RESULTS FROM THE PHASE 2 GMMG-DANTE TRIAL

Background: Renal function impairment is one of the main characteristics of multiple myeloma (MM) leading to diagnosis and defining treatment requirement in first-line and subsequent relapse. However, limited data exist on safety and efficacy of anti-MM regimens in patients (pts) with severe renal impairment and those requiring hemodialysis as pts are mostly excluded from clinical trials and specific trials in this indication are rare. Proteasome inhibitors as bortezomib (BTZ) are known to represent one of the preferable drug classes in patients with renal impairment due to rapid response, lack of dose adjustment and renoprotective effects. Daratumumab (DARA) is an anti-CD38 monoclonal antibody which enhances response rates and efficacy when added to standard of care regimens, both in newly diagnosed and relapsed and refractory (RR)MM. The combination of BTZ, dexamethasone (DEX), and DARA (DVd) has been shown to be efficacious and safe in RRMM in the phase 3 study CASTOR (Palumbo et al., NEJM 2016). In the CASTOR trial, pts with a GFR < 20 ml/min were excluded. Aims: Here, we present results from the primary analysis of the investigator-initiated multicenter GMMG-DANTE (NCT02977494) trial investigating DVd in RRMM pts with severe renal impairment including pts on hemodialysis. Methods: RRMM pts with measurable disease who had received at least 1 prior line of therapy and a GFR < 30 ml/min or undergoing hemodialysis were eligible. Pts received DVd in the approved schedule with 8 cycles (21 d/cycle) of BTZ (1.3 mg/m2, SC) on Days 1, 4, 8, and 11 and DEX (20 mg, PO or IV) on days 1, 2, 4, 5, 8, 9, 11, and 12 + DARA (16 mg/kg, IV) given weekly for cycles 1-3, Q3W for cycles 4-8, and Q4W thereafter. 36 patients were planned to be included into the trial. The trial was closed prematurely after 22 patients due to inferior recruitment. The primary endpoint was overall response rate (ORR). Key secondary endpoints were progression-free survival (PFS), overall survival (OS) and safety. Response assessment was performed using the IMWG criteria. Results: 22 pts from 6 German and one Greek site were included from 2017-2020. Analyzed population included 21 patients. Median age was 70 years. Median GFR was 21.0 ml/min, 8 patients were under hemodialysis. Median number of prior lines was 2 (range 1-10). All patients started DVd treatment. For one patient it was not possible to obtain a response. ORR was 67% (14/20) with 6 pts (29%) showing a partial response (PR), 6 pts (29%) a very good partial response (VGPR) and 2 pts (10%) a complete response (CR). Median treatment duration was 24 weeks (range 2-106). After a median follow-up of 28 months, median PFS was 10.4 months, median OS was not reached (OS after 24 months until 39 months plateau 0.504). The most frequent toxicity ≥ grade 3 was hematologic, with anemia in 23.8%, thrombocytopenia in 23.8% and neutropenia in 9.5%. Main non-hematologic adverse events (AEs) ≥ grade 3 were infections (23.8%) with mainly pneumonias. Polyneuropathy all grade was described in 52.4%. Summary/Conclusion: In this phase II prospective trial we demonstrated that DVd shows relevant efficacy in RRMM pts with severe renal impairment and can be safely administered. Efficacy is comparable to the one reported in patients with no severe renal impairment. Toxicity does not differ from previously reported data on DVd. Acknowledging the generally reported impaired outcome of MM pts showing severe renal impairment, PFS and OS underline the importance of effective MM regimens which can be safely administered in a difficult to treat population.

Systematic Review of Neoadjuvant Immunotherapy for Patients With Non–Small Cell Lung Cancer

There is a paucity of robust clinical evidence for the role of neoadjuvant immunotherapy in patients with resectable non-small cell lung cancer. The primary aim of the study was to identify the available data on the feasibility, safety and efficacy of neoadjuvant immunotherapy. A systematic review was conducted using electronic databases. Relevant studies were identified according to predefined selection criteria. Five relevant publications on 4 completed trials were identified. In most studies, >90% of patients were able to undergo surgery within the planned timeframe after neoadjuvant immunotherapy. There was a high incidence of open thoracotomy procedures, either planned or converted from a planned minimally invasive approach. Mortality ranged from 0 to 5%, but none of the reported deaths were considered directly treatment-related. Morbidities were reported according to adverse events related to neoadjuvant systemic therapy, and postoperative surgical complications. Survival outcomes were limited due to short follow-up periods. Major pathologic response ranged from 40.5 to 56.7%, whilst complete pathologic response of the primary tumor ranged from 15 to 33%. Radiological responses were reported according to RECIST criteria and fluorodeoxyglucose-avidity. This systematic review reported safe perioperative outcomes of patients who underwent resection following neoadjuvant immunotherapy. However, there was a relatively high incidence of open thoracotomy procedures, partly due to the technical challenges associated with increased fibrosis and inflammation of tissue, as well as the more advanced stages of disease in patients enrolled in the studies. Future studies should focus on identifying predictors of pathological response.

Subcutaneous Daratumumab (DARA SC) Plus Standard-of-Care (SoC) Regimens in Multiple Myeloma (MM) across Lines of Therapy in the Phase 2 Pleiades Study: Initial Results of the Dara SC Plus Carfilzomib/Dexamethasone (D-Kd) Cohort, and Updated Results for the Dara SC Plus Bortezomib/Melphalan/Prednisone (D-VMP) and Dara SC Plus Lenalidomide/Dexamethasone (D-Rd) Cohorts

Subcutaneous Daratumumab (DARA SC) Plus Standard-of-Care (SoC) Regimens in Multiple Myeloma (MM) across Lines of Therapy in the Phase 2 Pleiades Study: Initial Results of the Dara SC Plus Carfilzomib/Dexamethasone (D-Kd) Cohort, and Updated Results for the Dara SC Plus Bortezomib/Melphalan/Prednisone (D-VMP) and Dara SC Plus Lenalidomide/Dexamethasone (D-Rd) Cohorts

Daratumumab, Bortezomib, Dexamethasone (D-Vd) Versus Bortezomib and Dexamethasone (Vd) in Relapsed or Refractory (RR) Multiple Myeloma (MM): Pooled Subgroup Analysis of Lepus and Castor

Daratumumab, Bortezomib, Dexamethasone (D-Vd) Versus Bortezomib and Dexamethasone (Vd) in Relapsed or Refractory (RR) Multiple Myeloma (MM): Pooled Subgroup Analysis of Lepus and Castor

Sustained Minimal Residual Disease (MRD) Negativity and Clinical Efficacy in Transplant-Ineligible (TIE) Newly Diagnosed Multiple Myeloma (NDMM) Patients (Pts) Treated with Daratumumab-Based Regimens: Analysis of Maia and Alcyone

Sustained Minimal Residual Disease (MRD) Negativity and Clinical Efficacy in Transplant-Ineligible (TIE) Newly Diagnosed Multiple Myeloma (NDMM) Patients (Pts) Treated with Daratumumab-Based Regimens: Analysis of Maia and Alcyone

Long-Term Outcomes and Health-Related Quality of Life (HRQoL) By Response Status for Bortezomib, Melphalan, and Prednisone (VMP) ± Daratumumab (DARA) in Alcyone

Long-Term Outcomes and Health-Related Quality of Life (HRQoL) By Response Status for Bortezomib, Melphalan, and Prednisone (VMP) ± Daratumumab (DARA) in Alcyone

Efficacy and Safety of Daratumumab, Bortezomib, and Dexamethasone (D-Vd) Versus Bortezomib and Dexamethasone (Vd) in First Relapse Patients (pts) with Multiple Myeloma (MM): Four-Year Update of Castor

Efficacy and Safety of Daratumumab, Bortezomib, and Dexamethasone (D-Vd) Versus Bortezomib and Dexamethasone (Vd) in First Relapse Patients (pts) with Multiple Myeloma (MM): Four-Year Update of Castor

TPExtreme randomized trial: TPEx versus Extreme regimen in 1st line recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC).

6002 Background: After promising results from the GORTEC TPEx phase II trial, the role of taxane instead of 5FU in 1st-line R/M HNSCC chemotherapy (CT) remained to be confirmed by comparing TPEx to the reference EXTREME regimen. Methods: Randomized (1:1), open-label trial. Main inclusion criteria were R/M HNSCC not suitable for locoregional treatment, age 18-70 years, PS &lt;2, creatinine clearance &gt;60ml/min, prior cisplatin &lt;300 mg/m². Reference EXTREME regimen (arm A: 6 cycles every 3 weeks (Q3W) of 5FU–cisplatin-cetuximab (cetux) followed by weekly cetux maintenance) was compared to TPEx regimen (arm B: 4 cycles Q3W of docetaxel 75mg/m²–cisplatin 75mg/m²- cetux 250mg/m² with mandatory G-CSF support followed by every 2W cetux 500mg/m² maintenance). The primary endpoint was Overall Survival (OS). To detect a hazard ratio (HR) of 0.72 (median OS increase from 10.1 to 14.0 months (mo) with 88% power, 2-sided significance level of 0.05, 374 deaths were required. 540 patients (pts) were planned to enroll. Results: 539 pts were enrolled in 37 mo. Median age was 60 years, 93% were smokers, 40% had oropharyngeal tumor (p16 or HPV DNA was done in 85%, positive in 28%). In arm A, 44% of pts received all CT cycles vs 72% in arm B. Delays in administration were more frequent in arm A (27% vs 10%). Cisplatin was more frequently switched to carboplatin in arm A (34% vs 9%). Toxicity was lower in arm B: 34% pts had grade ≥4 adverse events during CT in arm B vs 50% in arm A (p&lt;0.001). Less pts in arm A started maintenance than in arm B (53% vs 73%). At time of analysis, the median follow-up duration was 30 mo and 406 pts had died. OS was not significantly different between arms: HR=0.87 (95%CI: 0.71-1.05), p=0.15. Median OS was 13.4 mo in arm A vs 14.5 in arm B. 2-year OS rate was 21.0% in arm A vs 28.6% in arm B. Conclusions: This large randomized trial confirmed the encouraging survival results of the TPEx regimen observed in the first phase II. OS in both arms was higher than observed in previous randomized CT or immunotherapy combination trials. Despite lack of significant OS increase, taxane based TPEx regimen appears to be a new option in 1st line R/M HNSCC, with a shorter time on CT and significantly lower toxicity than the EXTREME regimen. Clinical trial information: NCT02268695.

Evaluation of Sustained Minimal Residual Disease (MRD) Negativity in Relapsed/Refractory Multiple Myeloma (RRMM) Patients (Pts) Treated with Daratumumab in Combination with Lenalidomide Plus Dexamethasone (D-Rd) or Bortezomib Plus Dexamethasone (D-Vd): Analysis of Pollux and Castor

Evaluation of Sustained Minimal Residual Disease (MRD) Negativity in Relapsed/Refractory Multiple Myeloma (RRMM) Patients (Pts) Treated with Daratumumab in Combination with Lenalidomide Plus Dexamethasone (D-Rd) or Bortezomib Plus Dexamethasone (D-Vd): Analysis of Pollux and Castor

Efficacy and Safety of Daratumumab, Bortezomib, and Dexamethasone (D-Vd) Versus Bortezomib and Dexamethasone (Vd) in First Relapse Patients: Two-Year Update of Castor

Efficacy and Safety of Daratumumab, Bortezomib, and Dexamethasone (D-Vd) Versus Bortezomib and Dexamethasone (Vd) in First Relapse Patients: Two-Year Update of Castor

One-Year Update of a Phase 3 Randomized Study of Daratumumab Plus Bortezomib, Melphalan, and Prednisone (D-VMP) Versus Bortezomib, Melphalan, and Prednisone (VMP) in Patients (Pts) with Transplant-Ineligible Newly Diagnosed Multiple Myeloma (NDMM): Alcyone

One-Year Update of a Phase 3 Randomized Study of Daratumumab Plus Bortezomib, Melphalan, and Prednisone (D-VMP) Versus Bortezomib, Melphalan, and Prednisone (VMP) in Patients (Pts) with Transplant-Ineligible Newly Diagnosed Multiple Myeloma (NDMM): Alcyone

Comparative Efficacy and Safety of Daratumumab in Combination with Bortezomib, Melphalan, and Prednisone (D-VMP) in Alcyone Versus Bortezomib, Melphalan, and Prednisone (VMP) in Vista in Newly Diagnosed Multiple Myeloma (NDMM) Patients Using Propensity Score Matching (PSM)

Comparative Efficacy and Safety of Daratumumab in Combination with Bortezomib, Melphalan, and Prednisone (D-VMP) in Alcyone Versus Bortezomib, Melphalan, and Prednisone (VMP) in Vista in Newly Diagnosed Multiple Myeloma (NDMM) Patients Using Propensity Score Matching (PSM)

Phase 3 Randomized Study of Daratumumab Plus Bortezomib, Melphalan, and Prednisone (D-VMP) Versus Bortezomib, Melphalan, and Prednisone (VMP) in Newly Diagnosed Multiple Myeloma (NDMM) Patients (Pts) Ineligible for Transplant (ALCYONE)

Phase 3 Randomized Study of Daratumumab Plus Bortezomib, Melphalan, and Prednisone (D-VMP) Versus Bortezomib, Melphalan, and Prednisone (VMP) in Newly Diagnosed Multiple Myeloma (NDMM) Patients (Pts) Ineligible for Transplant (ALCYONE)

Safety and efficacy of daratumumab-based regimens in elderly (≥75 y) patients (Pts) with relapsed or refractory multiple myeloma (RRMM): Subgroup analysis of POLLUX and CASTOR.

8033 Background: Daratumumab (D) plus lenalidomide and dexamethasone (Rd; POLLUX) or with bortezomib and dexamethasone (Vd; CASTOR) demonstrated prolonged PFS and tolerability compared with Rd and Vd alone, respectively, in RRMM pts. We examined the safety and efficacy profiles of DRd and DVd in elderly (≥75 y) pts from these phase 3 studies. Methods: Pts with ≥1 prior line of therapy were enrolled. All pts in POLLUX were treated until progression; CASTOR pts received 8 cycles of Vd ± daratumumab. Different D (16 mg/kg) dosing schedules were used in POLLUX (qw for cycles 1-2, q2w for cycles 3-6, and q4w thereafter) and CASTOR (qw in Cycles 1-3, q3w for Cycles 4-8, and q4w thereafter). Elderly pts received a reduced dexamethasone dose (20 mg once weekly). Results: In POLLUX, 29/286 (DRd) and 35/283 (Rd) were ≥75 y, with 86% and 91% having ECOG status ≤1, respectively. With 17.3 months of median follow up, 10% in DRd and 11% in Rd discontinued due to treatment-emergent adverse events (TEAEs). Common (&gt;10%) grade 3/4 TEAEs for DRd included neutropenia and hypokalemia (Table). Twelve (41%) DRd pts experienced infusion-related reactions (IRR) and 4 (14%) experienced grade 3/4 IRR; none discontinued due to IRR. Median PFS was not reached (NR) in DRd vs 11.4 months in Rd (HR 0.19; 95% CI, 0.06-0.55; P=0.0007), and ≥CR % was significantly higher with DRd vs Rd (52% vs 9%; P=0.0002). In CASTOR, 23/251 (DVd) and 35/247 (Vd) were ≥75 y, with 100% and 94% having ECOG status ≤1, respectively. With 13.0 months of median follow up, rates of discontinuation due to TEAEs were similar (15% vs 20%). Thrombocytopenia, fatigue, and pneumonia were common grade 3/4 TEAEs for DVd (Table). Thirteen (65%) pts reported IRR (10% grade 3/4) and no pts discontinued due to IRR. Median PFS was NR in DVd vs 8.1 months in Vd (HR 0.27; 95% CI, 0.12-0.61; P=0.0007), and significantly higher ≥CR % was observed in DVd vs Vd (25% vs 3%; P=0.0154). Conclusions: The safety and efficacy profiles in elderly pts were generally comparable with the overall population in each study. Clinical trial information: NCT02136134 and NCT02076009. [Table: see text]

Abstract P4-21-42: MetaPHER phase IIIb multicenter, open-label, single-arm safety study of subcutaneous trastuzumab in combination with pertuzumab and docetaxel in patients with HER2-positive advanced breast cancer: First results

Abstract Background: MetaPHER investigates fixed-dose subcutaneous trastuzumab (Herceptin® [H SC]) in combination with intravenous (IV) pertuzumab (PERJETA® [P IV]) plus docetaxel (D IV). The MetaPHER study treatment regimen is based on CLEOPATRA (phase III; NCT00567190), which demonstrated a significant progression-free and overall survival benefit in patients (pts) with HER2-positive metastatic breast cancer (BC) following first-line treatment with IV trastuzumab (Herceptin® [H IV]) plus P IV plus D IV. Fixed-dose H SC was non-inferior to H IV in terms of pathological complete response and serum trough concentration, and had a comparable safety profile to H IV, in pts with HER2-positive early BC in HannaH (phase III; NCT00950300). Furthermore, PrefHer (NCT01401166) results showed compelling patient preference for H SC vs H IV (88.9% vs 9.6%) in the HER2-positive early BC setting. To date, limited data exist for H SC in combination with P IV and D IV; we report the first results of safety and tolerability from MetaPHER for this combination in pts with HER2-positive advanced BC. Methods: MetaPHER enrollment is ongoing at &amp;gt;100 sites in 12 countries. Females aged ≥18 years with metastatic or locally recurrent HER2-positive BC previously untreated with non-hormonal anticancer therapy, an Eastern Cooperative Oncology Group performance status of 0 or 1, and left ventricular ejection fraction (LVEF) ≥50% receive fixed-dose H SC 600 mg/5 mL q3w, P IV (840 mg loading dose, then 420 mg at subsequent cycles q3w), and D IV (at least 6 cycles with a recommended initial dose of 75 mg/m2 q3w; possible escalation to 100 mg/m2 q3w and continuation of D IV after Cycle 6 at the investigator's discretion). Study treatment is given until disease progression, unacceptable toxicity, withdrawal of consent, death, or predefined study end, whichever occurs first. The primary endpoint is safety and tolerability of H SC in combination with P IV and D IV in pts with HER2-positive advanced BC. Adverse events (AEs) and serious AEs (SAEs) were graded per National Cancer Institute – Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.0. Results are descriptive. Results: 150 pts were enrolled and received a median of 4 treatment cycles by the data cutoff date of June 23, 2016. Safety data are shown in the table. Pts with ≥1 event, n (%)H SC + P IV + D IV (N = 150)Any grade AEs136 (90.7)Grade ≥3 AEs59 (39.3)SAEs23 (15.3)Deaths2 (1.3)AEs leading to discontinuation of H SC, P IV, or D IV16 (10.7)AEs leading to discontinuation of H SC5 (3.3)AEs of Interest Administration-related and local injection-site reactions for H SC5 (3.3)*Cardiac: Grade ≥3 cardiac AEs†1 (0.7)Any grade congestive heart failure‡0Pts with a significant LVEF drop§1 (0.7)*Grade 1 &amp; 2 AEs only; †Events classified as System Organ Class Cardiac Disorders; ‡Preferred terms of reported AEs; §≥10% from baseline to LVEF &amp;lt;50%. Conclusion: MetaPHER's first report of H SC with P IV and D IV as first-line treatment for pts with HER2-positive advanced BC is consistent with the known safety profile for H IV with P IV and D IV from CLEOPATRA, and no new safety signals were identified. Citation Format: Kümmel S, Abraham J, Martin M, Crepelle-Fléchais A, Swat A, Nüesch E, Shing M, Tondini CA. MetaPHER phase IIIb multicenter, open-label, single-arm safety study of subcutaneous trastuzumab in combination with pertuzumab and docetaxel in patients with HER2-positive advanced breast cancer: First results [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P4-21-42.

Pertuzumab plus trastuzumab in combination with standard neoadjuvant anthracycline-containing and anthracycline-free chemotherapy regimens in patients with HER2-positive early breast cancer: a randomized phase II cardiac safety study (TRYPHAENA)

BackgroundPertuzumab (P) combined with trastuzumab (H)-based chemotherapy improves efficacy in early and advanced HER2-positive breast cancer. We assessed the tolerability, with particular focus on cardiac safety, of H and P with chemotherapy in the neoadjuvant treatment of HER2-positive early breast cancer. Patients and methodsIn this multicenter, open-label phase II study, patients with operable, locally advanced, or inflammatory breast cancer were randomized 1 : 1 : 1 to receive six neoadjuvant cycles q3w (Arm A: 5-fluorouracil, epirubicin, cyclophosphamide [FEC] + H + P ×3 → docetaxel [T] + H + P ×3; Arm B: FEC ×3 → T + H + P ×3; Arm C: T + carboplatin + H [TCH]+P ×6). pCR was assessed at surgery and adjuvant therapy given to complete 1 year of H. ResultsTwo hundred twenty-five patients were randomized. During neoadjuvant treatment, two patients (2.7%; Arm B) experienced symptomatic left ventricular systolic dysfunction (LVSD) and 11 patients (Arm A: 4 [5.6%]; Arm B: 4 [5.3%]; Arm C: 3 [3.9%]) had declines in left ventricular ejection fraction of ≥10% points from baseline to <50%. Diarrhea was the most common adverse event. pCR (ypT0/is) was reported for 61.6% (Arm A), 57.3% (Arm B), and 66.2% (Arm C) of patients. ConclusionThe combination of P with H and standard chemotherapy resulted in low rates of symptomatic LVSD.

1247P - Randomised Phase II Trial of Oral Vinorelbine (N) and Cisplatin (P) or Pemetrexed and C (PC) in First Line Advanced Non Squamous (NSCC) Non Small Cell Lung Cancer (NSCLC) Patients (PTS). Navotrial01: Final Results

ABSTRACT Background Individualized treatments in NSCLC are now based on molecular and/or histological data. This randomized trial (2/1) was set up to assess the efficacy of NC compared to PC for pts with nSCC. The primary end-point was disease control rate (DCR) including overall response rate (ORR) and stable disease (SD). Methods Pts received N60-80 mg/m2 D1, D8 + C80 mg/m2 D1 or P500 mg/m2 + C75 mg/m2 D1 for 4 cycles q3w; pts with DCR received single agent continuation maintenance (CM) until progression or toxicity. Results From 10/09 to 02/11, 151 pts were treated with NC or PC. ITT = 151 NC n = 100 PC n = 51 Male/Stage IV (%) 62.0/87.0 64.7/88.2 Median age (y, range) 61.0 (38.4-75.1) 63.8 (40.3-75.5) Combination: (%) ITT(95% CI) DCR 75.0 (65.3-83.1) 74.5 (60.4-85.7) ORR 21.0 (13.5-30.3) 23.5 (12.8-37.5) Combination + CM:(%) ITT (95% CI) n= 53 n = 33 DCR 75 (65.3-83.1) 76.5 (62.5-87.2) ORR 24 (16.0-33.6) 31.4 (19.1-45.9) Median PFS ITT (m,range) 4.2 (3.6-4.7) 4.2 (3.2-5.6) PFS ITT at 6/12/18m (%) 33.0/10.3/5.5 27.5/7.4/2.5 Median OS ITT (m,range) 10.6 (7.8-12.1) 10.8 (7.0-14.5) Related toxicities G3/4 (%pts) NC/PC during Combination: anemia 9.0(G3)/8.2, leucopenia 26.0/10.2, neutropenia 44.0/18.3, febrile neutro 2.0/2.0, thrombocytopenia 0/6.1, fatigue(G3) 7.0/3.9, hyperglycemia 4.0/7.8, nausea(G3) 5.0/0, vomiting(G3) 7.0/2.0, stomatitis(G3) 0/2.0, pneumonia(G3) 0/2.0, deep vein thrombosis(G3) 0/2.0, pulmonary embolism(G4) 0/2.0. During Maintenance: anemia 5.0/4.1, leucopenia 2.0/10.2, neutropenia 11.0/20.4, febrile neutro 3.8/0, fatigue (G3) 3.8/0, stomatitis(G3) 1.9/ 3.0, pain 3.8/6.0, Respiratory disorders 0/4.0, deep vein thrombosis (G3)0/2.0. Deaths potentially related to CT 2/1. Conclusions NC and PC had similar efficacy. In the present economic context, the acquisition cost of the two platinum based doublets should be considered in the treatment decision making of pts with advanced nSCC NSCLC. Disclosure S. Malasse: Statistician of the study Employment for the sponsor. F. Biville-Hedouin: Medical Project Manager of the study Employment for the sponsor. All other authors have declared no conflicts of interest.

A randomized phase II study of paclitaxel (P) and carboplatin (C) ± bevacizumab (B) ± dulanermin (D) in non-small cell lung cancer (NSCLC).

7534 Background: D is a pro-apoptotic agonist of death receptors 4 and 5. A randomized, open-label, 5-arm, phase II study evaluated the efficacy and safety of PC ± B ± D in patients (pts) with advanced NSCLC. Methods: Planned sample size = 200 (40/arm). Eligible pts: chemonaïve, advanced NSCLC, ECOG PS 0-1. A brain scan was mandatory. Pts received P (200 mg/m2) + C (AUC = 6 mg/mL min). Pts with squamous NSCLC and/or CNS metastases (met) received PC (Arm 1) vs. PC + D (8 mg/kg for 5 days; Arm 2). Pts with non-squamous NSCLC and no CNS met received PC + B (15 mg/kg; Arm 3) vs. PCB + D (8 mg/kg for 5 days; Arm 4) vs. PCB + D (20 mg/kg for 2 days; Arm 5). Pts received PC ± B ± D ≤ 6 cycles Q3W, then continued B and/or D until disease progression. Primary endpoint: objective response rate (ORR; central assessment of complete and partial responses by modified RECIST). Results: 213 pts were randomized (41, 42, 44, 43, 43 to arms 1-5); all were eligible; 41, 39, 42, 40, 41 received ≥ 1 dose of study drug. Median age was 60 (range 23-79) years, 63% were men, 42% were ECOG PS 0. As of 10/09, 194 pts (dosed; 96%) had discontinued treatment; median follow-up = 49 (range 0-91) wks. See Table for efficacy and safety. The most common serious adverse events (SAE) were pneumonia and pulmonary embolism (each = 4%). Conclusions: PC ± D ± B was well tolerated. In this study, the addition of D did not appear to improve efficacy compared with the standard treatment arms. Squamous NSCLC and/or CNS met Nonsquamous NSCLC and no CNS met 1: PC 2: PC + D 2 vs. 1 3: PCB 4: PCB + D 5: PCB + D 4 vs. 3 5 vs. 3 ORR 16(39%) 16 (38%) OR = 1.04 (0.39, 2.76), p = 1 22 (50%) 17 (40%) 17 (40%) OR = 1.53 (0.6, 3.91), p = 0.39 OR = 1.53 (0.6-3.91), p = 0.39 PFS events; KM median (95% CI), mo 85%; 6.1 (5.4-7.4) 76%; 5.5 (4.7-6.7) HR = 0.89 (0.54, 1.46), p = 0.65 68%; 7.3 (5.6, 8.5) 63%; 8.6 (6, 12.6) 63%; 9.5 (6.8, 13.7) HR = 0.83 (0.49, 1.40), p = 0.48 HR = 0.88 (0.52, 1.48), p = 0.62 OS events; KM median (95% CI), mo 61%; 10.1 (8.2, NE) 60%; 9.8 (5.9, 16.4) HR = 1.14 (0.66, 1.99) p = 0.64 52%; 15.1 (9, NE) 51%; 13.9 (11.4, 18.3) 56%; 14.3 (10, 16.1) HR = 1.03 (0.57, 1.86) p = 0.92 HR = 1.04 (0.59, 1.85) p = 0.89 AE 37 (90%) 36 (92%) 41 (98%) 40 (100%) 39 (95%) Grade ≥ 3 AE 17 (41%) 30 (77%) 29 (69%) 23 (58%) 30 (73%) SAE 11 (27%) 22 (56%) 19 (45%) 18 (45%) 18 (44%) Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Amgen Amgen, Roche Amgen Amgen, Roche Amgen