Influence of radiation field on safety and efficacy for stage II/III esophageal cancer treated with definitive chemoradiotherapy: An exploratory analysis of JCOG0909.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 104-104
Author(s):  
Azusa Komori ◽  
Shuichi Hironaka ◽  
Ryunosuke Machida ◽  
Yoshinori Ito ◽  
Hiroya Takeuchi ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Lymph Nodes ◽  
Regional Lymph Node ◽  
Progression Free Survival ◽  
Complete Response ◽  
Tumor Location ◽  
Efficacy And Safety ◽  
Definitive Chemoradiotherapy ◽  
Safety And Efficacy ◽  
Upper Thoracic

104 Background: JCOG0909, a single-arm confirmatory trial of definitive chemoradiotherapy (dCRT) including salvage treatment, demonstrated promising efficacy and safety for cStage II/III (UICC-TNM 6th) esophageal cancer (EC) (Ito Y, ASCO 2018). Radiation (RT) fields included the elective regional lymph node during initial 41.4 Gy, such as bilateral supraclavicular fossae and superior mediastinal lymph nodes for upper thoracic (Ut), and mediastinal and perigastric lymph nodes for middle thoracic (Mt)/lower thoracic (Lt) EC. It is unclear whether the safety and efficacy are associated with the tumor location in patients with cStage II/III EC treated with dCRT. Methods: Patients who were enrolled in JCOG0909 and underwent dCRT were analyzed. Patients were categorized into three groups according to primary tumor location (Ut/Mt/Lt). We compared adverse events during dCRT, complete response (CR) rate, progression-free survival (PFS) and overall survival (OS) among groups. Results: Ninety-four patients (Ut/Mt/Lt: 16/59/19) were analyzed. The proportions of cStage IIA/IIB/III were 31%/44%/25% in Ut group, 20%/42%/37% in Mt group, and 21%/32%/47% in Lt group, respectively. The summary of safety and efficacy was listed in Table 1. Grade 3-4 leukopenia, neutropenia and thrombocytopenia were more frequently observed in Mt and Lt groups than in Ut group. CR rate was 63% in Ut, 63% in Mt, and 42% in Lt, respectively. 3-year PFS in Ut/Mt/Lt was 60%/59%/47% and 3-year OS was 73%/78%/58%, respectively. Conclusions: The RT field by the tumor location might be associated with efficacy and safety of dCRT for cStage II/III esophageal cancer. [Table: see text]

Isatuximab plus carfilzomib and dexamethasone in east Asian patients with relapsed multiple myeloma: IKEMA subgroup analysis.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e20015-e20015
Author(s):  
Kihyun Kim ◽  
Chang Ki Min ◽  
Youngil Koh ◽  
Kenichi Ishizawa ◽  
Sung-Hyun Kim ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Disease Progression ◽  
Residual Disease ◽  
East Asian ◽  
Progression Free Survival ◽  
Complete Response ◽  
Efficacy And Safety ◽  
Asian Patients ◽  
Number Of Patients ◽  
East Asian Patients

e20015 Background: The Phase 3 IKEMA study (NCT03275285) demonstrated that isatuximab (Isa) plus carfilzomib and dexamethasone (Kd) significantly improved progression-free survival (PFS) compared with Kd in patients (pts) with relapsed multiple myeloma (RMM) (hazard ratio [HR] 0.53; 99% confidence interval [CI] 0.32–0.89; P= 0.0007). We evaluated the efficacy and safety of Isa-Kd in the East Asian patients (19 Japanese, 27 Korean). Methods: RMM pts who received 1-3 prior lines of therapy were stratified to receive Isa-Kd or Kd. Isa-Kd arm received Isa (10 mg/kg intravenously) weekly for 4 weeks, then every 2 weeks. Both arms received K (20 mg/m2 days 1-2, 56 mg/m2 thereafter) twice-weekly for 3 of 4 weeks, and d (20 mg) twice-weekly. Treatment continued until disease progression or unacceptable adverse events (AE). The primary endpoint was prolongation of PFS. Key secondary endpoints included; very good partial response or better (≥VGPR), complete response (CR) rate and minimal residual disease negativity (MRD–) rate. Results: East Asian pts (25 Isa-Kd, 21 Kd) were randomized. Pt characteristics were similar in the East Asian subgroup compared with the intent to treat (ITT) population (N = 302). Median age (Isa-Kd 64.0 [range 45–83] years vs Kd 60.0 [range 33–73] years); median prior lines Isa-Kd 2.0 (range 1–3) vs Kd 1.0 (range 1–3); refractory to lenalidomide 16.0% Isa-Kd vs 47.6% Kd; refractory to PI 20.0% Isa-Kd vs 33.3% Kd; high-risk cytogenetics 48.0% Isa-Kd vs 42.9% Kd. After a median follow-up of 20.7 months, the addition of Isa to Kd improved ≥VGPR, CR and MRD– rates (Table). The HR 0.64 (95%CI: 0.231-1.764) for disease progression or death favored Isa-Kd. Grade ≥3 AEs were observed in 79.2% Isa-Kd vs 55.0% Kd pts, serious TEAEs in 45.8% Isa-Kd vs 50.0% Kd; TEAEs leading to treatment discontinuation were lower in the Isa-Kd group (4.2% Isa-Kd vs 10.0% Kd). Overall, 64.0% Isa-Kd vs 42.9% Kd pts were still receiving treatment. Conclusions: Efficacy and safety results of Isa-Kd in East Asian pts are consistent with the results of the overall IKEMA population, in which significantly better efficacy (PFS, CR, ≥VGPR and MRD– rate) was reported in favor of Isa-Kd without an increase in the number of patients with serious TEAEs or discontinuations. Isa-Kd is a potential treatment option for East Asian pts with RMM. Clinical trial information: NCT03275285. [Table: see text]

Retrospective Review of Safety and Efficacy of Anlotinib in Advanced Osteosarcoma With Metastases After Failure of Standard Multimodal Therapy

2021 ◽  
Author(s):  
Hanqing Li ◽  
Yang Li ◽  
Lei Song ◽  
Qiuchi Ai ◽  
shuai zhang
Keyword(s):  
Adverse Events ◽  
Multimodal Therapy ◽  
Objective Response ◽  
Progression Free Survival ◽  
Complete Response ◽  
Free Survival ◽  
Safety And Efficacy ◽  
Common Drug ◽  
Grade 3 ◽  
Therapeutic Doses

Abstract To study and observe the safety and efficacy of anlotinib in the treatment of advanced osteosarcoma with metastases. We retrospectively studied patients with advanced osteosarcoma and metastases who received anlotinib treatment in our hospital from June 2018 to April 2020. All patients had received standard multimodal therapies, before taking anlotinib. Therapeutic doses of anlotinib were 12 mg for adults and 10 mg for children and adolescents once a day for 2 consecutive weeks, followed by a week of withdrawal. This 3-week cycle of treatment was continued until the tumor progressed rapidly or the patients failed to tolerate the side effects. Adverse drug reactions were recorded, and therapeutic efficacy was evaluated based on progression free survival (PFS), disease control rate (DCR), overall survival (OS), and objective response rate (ORR). The median PFS was 9.81 ± 0.9 months, and the 6-month and 10-month PFS rates were 73.3% and 33.3%, respectively. The median OS was 11.43 ± 0.58 months. No patients achieved complete response. After 6 months of treatment, the DCR and ORR were 80% and 13.3%, respectively. No drug-related deaths or Grade 4 adverse events occurred in the patients. Five patients (33.3%) had Grade 3 adverse events. The most common drug-related adverse events were hand-food syndrome, fatigue, high blood pressure, anorexia, and pneumothorax. Anlotinib had a certain curative effect on patients with advanced osteosarcoma and metastases after failure of standard treatment. The adverse events were mostly tolerable or relieved after treatment.

PS02.038: SAFETY AND EFFICACY OF REPETITIVE PHOTODYNAMIC THERAPY FOR RESIDUAL ESOPHAGEAL CANCER LESIONS AFTER INITIAL PHOTODYNAMIC THERAPY

2018 ◽  
Vol 31 (Supplement_1) ◽  
pp. 130-131
Author(s):  
Masashi Tamaoki ◽  
Yusuke Amanuma ◽  
Takahiro Horimatsu ◽  
Shinya Ohashi ◽  
Manabu Muto
Keyword(s):  
Esophageal Cancer ◽  
Photodynamic Therapy ◽  
Conflicts Of Interest ◽  
Complete Response ◽  
Best Supportive Care ◽  
Local Failure ◽  
University Hospital ◽  
Safety And Efficacy ◽  
Lesion Depth ◽  
Talaporfin Sodium

Abstract Background Photodynamic therapy (PDT) is an effective salvage treatment for local failure after chemoradiotherapy in patients with esophageal cancers. However, the treatment strategy for local failure after initial PDT has not been established, and the safety and efficacy of repetitive PDT for such lesions are also unknown. Methods We retrospectively investigated 33 esophageal cancer patients who received initial salvage PDT at Kyoto University Hospital between May 2012 and November 2017. Additionally, we examined the treatment outcomes of those patients who received repetitive PDT. Results Twenty-one patients (64%) achieved local complete response (CR) by initial PDT, and local recurrence did not occur in those patients. Eleven patients (33%) had residual lesions after initial PDT. Among these, 7 patients were treated with repetitive PDT, 2 patients selected best supportive care, 1 patient was treated with surgery, and 1 patient was treated with chemotherapy. Five of the 7 patients who received repetitive PDT were treated with talaporfin sodium, and 2 patients were treated with porfimer sodium. The median age of the patients who received repetitive PDT was 70 years old, and all patients were men. Regarding histology, 6 patients were squamous cell carcinoma and 1 patient was adenocarcinoma. The median period from initial PDT to repetitive PDT was 3 months (range 1–4). Lesion depth before initial PDT was T1 in 3 patients and T2 in 4 patients. Lesion depth before repetitive PDT was T1 in 5 patients, and T2 in 2 patients. Local CR rate in 7 patients treated with repetitive PDT was 42.9% (3/7). Additionally, local CR rate in T1 cases was 60% and 0% in T2 cases. Adverse events of grade 3 or higher were not observed in any patient. Conclusion Repetitive salvage PDT was considered to be an effective and safe treatment option in residual T1 lesions after initial PDT for local failure of esophageal cancer treated with chemoradiotherapy. Disclosure All authors have declared no conflicts of interest.

Salvage lymphadenectomy without esophagectomy is an option for recurrent or residual lymph nodes after definitive chemoradiotherapy for esophageal cancer

Esophagus ◽  
2014 ◽  
Vol 11 (3) ◽  
pp. 197-203 ◽  
Author(s):  
Satoru Matono ◽  
Hiromasa Fujita ◽  
Toshiaki Tanaka ◽  
Naoki Mori ◽  
Takeshi Nagano ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Lymph Nodes ◽  
Definitive Chemoradiotherapy ◽  
Salvage Lymphadenectomy

Phase II cisplatin, irinotecan, cetuximab and concurrent radiation therapy followed by surgery for locally advanced esophageal cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 4064-4064 ◽  
Author(s):  
P. C. Enzinger ◽  
T. Yock ◽  
W. Suh ◽  
P. Fidias ◽  
H. Mamon ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Radiation Therapy ◽  
Phase Ii ◽  
Locally Advanced ◽  
Complete Response ◽  
Tumor Location ◽  
Advanced Esophageal Cancer ◽  
Early Results ◽  
Ecog Ps ◽  
Locally Advanced Esophageal Cancer

4064 Background: Weekly irinotecan, cisplatin, and concurrent radiation therapy is a well-tolerated, active regimen in locally advanced esophageal cancer. (Ilson. JCO 2003) Cetuximab, an EGFR inhibitor, is a potent radiation sensitizer in head and neck cancer. (Bonner. Proc ASCO 2004) Methods: In this phase II trial, patients (pts) with T2–4N0–1M0–1A esophageal adenocarcinoma (A) or squamous cell carcinoma (S) receive 5040 cGy/28 fractions of radiation therapy (RT) and concurrent weekly cisplatin 30mg/m2 plus irinotecan 65 mg/m2 on weeks 1, 2, 4, and 5, followed by surgery 4–8 weeks after completion of RT. Additionally, pts receive weekly infusions of cetuximab 250 mg during RT, up to one week before surgery, and for 6 months following surgery. Results: Seventeen pts have been entered: male: female = 14:3, median age 54, ECOG PS 0:1 = 6:11, A:S = 17:0, stage IIA:IIB:III:IVA = 6:1:8:2, tumor location-esophagus-mid:lower:gastroesophageal junction = 1:4:12, >10% weight loss-yes:no = 8:9. Of 17 pts entered, 15 pts have proceeded to surgery, 1 pt died from Aspergillus infection resulting in respiratory failure and sepsis, and 1 pt is pending surgery. Of the 15 pts who underwent surgery, 2 (13%) had a complete pathologic response; pathologic stage for other pts: 0 = 1, I = 3, IIA = 3, IIB = 1, III = 4, IV = 1. Grade III/IV toxicity (17 pts) was: diarrhea 9 pts, neutropenia 9 pts, febrile neutropenia 5 pts, anorexia 5 pts, vomiting 4 pts, fatigue 3 pts, mucositis 1 pt. Chemotherapy dose attenuation was required for diarrhea in 5 pts, for neutropenia in 4 pts, and for folliculitis in 1 pt. One patient was removed from study during week 6 for prolonged diarrhea/ dehydration. Due to the 2-step design of the trial, accrual is on hold pending a 3rd required pathologic CR in the first 17 patients. Conclusions: Compared to other trials of irinotecan, cisplatin, radiation therapy, and surgery in similar groups of esophageal cancer patients, early results for this combination with cetuximab suggest a lower complete response rate and higher overall toxicity. Additional data will be available at ASCO. Supported by Bristol-Myers Squibb. No significant financial relationships to disclose.

Randomized phase II study of the safety and efficacy of a human anti-αv integrin monoclonal antibody (CNTO 95) alone and in combination with dacarbazine in patients with stage IV metastatic melanoma: 12-month results

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 9029-9029
Author(s):  
C. Loquai ◽  
A. Pavlick ◽  
D. Lawson ◽  
R. Gutzmer ◽  
J. Richards ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Research And Development ◽  
Metastatic Melanoma ◽  
Single Agent ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Complete Response ◽  
Open Label ◽  
Safety And Efficacy ◽  
To Receive

9029 Objectives: Evaluate the safety and efficacy of CNTO 95, a human anti-αv integrin monoclonal antibody, when administered alone or in combination with dacarbazine (DTIC). Methods: Patients with Stage IV metastatic melanoma were randomized 1:1:1:1 to receive 5 or 10mg/kg CNTO 95 alone, or DTIC (1000mg/m2) + either 10mg/kg CNTO 95 or placebo administered intravenously once every 3 weeks for 8 cycles in the absence of disease progression or unacceptable toxicity. DTIC arms were blinded; single-agent arms were open-label. The primary endpoint was progression free survival (PFS); secondary endpoints included partial response (PR), complete response (CR), stable disease (SD) and overall survival (OS). Major safety endpoints included the incidence of adverse events (AEs) and serious AEs (SAEs). Results: Patients were randomized to receive 5mg/kg CNTO 95 (n=32), 10mg/kg CNTO 95 (n=33), CNTO 95+DTIC (n=32), or placebo+DTIC (n=32). Baseline demographics were similar across groups. The median PFS for CNTO 95+DTIC was 75 days, placebo+DTIC was 54 days and both CNTO 95 alone arms were 42 days. Six patients achieved PR (2–10mg/kg CNTO 95, 1-CNTO 95+DTIC, 3-placebo+DTIC); one patient achieved CR (CNTO 95+DTIC). A higher proportion (43.3%) of patients achieved SD ≥ 12 wks in the CNTO 95+DTIC group compared with the other 3 groups (<20.0%). The median survival was 11.0 months for the patients in the CNTO 95+DTIC arm, 9.8 months and 14.9 months for the 5mg/kg and 10mg/kg arms, and 8.0 months for those in the DTIC control arm. The most common AEs were headache, nausea, fatigue, pyrexia, vomiting and transient uveitic reactions. Three patients (1–5mg/kg, 2-CNTO 95+DTIC) discontinued treatment due to AEs. A higher proportion of patients experienced SAEs in the placebo+DTIC group (29.0%) than in the 5mg/kg (12.9%), 10mg/kg (16.2%) or CNTO 95+DTIC (18.8%) groups. Conclusions: CNTO 95 alone or combined with DTIC was generally well tolerated. In patients with Stage IV metastatic melanoma, a trend toward improvement in PFS, OS and disease control was demonstrated with CNTO 95+DTIC. Centocor, Centocor Research and Development, Inc. Centocor Research and Development, Inc. Johnson & Johnson Centocor Research and Development, Inc. No significant financial relationships to disclose.

Modified FOLFIRINOX regimen in advanced biliary tract adenocarcinoma.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 484-484 ◽  
Author(s):  
Amit Rauthan ◽  
Poonam Patil
Keyword(s):  
Biliary Tract ◽  
Performance Status ◽  
Progression Free Survival ◽  
Complete Response ◽  
Tertiary Hospital ◽  
Efficacy And Safety ◽  
Good Performance Status ◽  
Pancreatic Cancers ◽  
Grade 3 ◽  
Dose Modifications

484 Background: The treatment of advanced biliary tract adenocarcinoma is based on chemotherapy with Gemcitabine with Cisplatin or Oxaliplatin in various combinations. After seeing the high efficacy of FOLFIRINOX regimen in advanced pancreatic cancers, we studied the efficacy and safety of a modified FOLFIRINOX regimen in advanced biliary tract adenocarcinoma. Methods: We retrospectively reviewed patient with advanced biliary tract adenocarcinoma who were treated with modified FOLFIRINOX regimen from April 2013 to March 2016 in a tertiary hospital. The schedule of modified FOLFIRINOX was - Oxaliplatin 85 mg/m2, Irinotecan 150 mg/ m2, Leucovorin 400 mg/m2, and 5 fluorouracil 2400 mg/m2given as a 46-hour continuous infusion, every 2 weeks. All patients received primary prophylactic growth factors. The objective was to evaluate the efficacy and safety of FOLFIRINOX regimen. Results: 20 patients with untreated advanced biliary tract adenocarcinoma were enrolled. The median age was 55 (range 31 to 66 years). All patients had good performance status. 2 patients had a complete response (10%), 8 patients had a partial response (40%), 5 patients had stable disease (25%) and 5 patients had progression (25%). The median progression free survival was 6 months and the median overall survival was 10 months. The major toxicities were grade 3/4 neutropenia (30%), oral mucositis (20%), fatigue (20%) and neuropathy (10%). Dose reduction was required in 30% patients. Conclusions: A modified FOLFIRINOX regimen is an effective regimen in good performance status patients with advanced biliary tract adenocarcinoma. Dose modifications are required to reduce toxicity of the regimen. It needs to be further studied in a phase 3 study in comparison to Gemcitabine based regimens.

The impact of primary tumor site on outcomes of treatment with etoposide and cisplatin in grade 3 gastroenteropancreatic neuroendocrine carcinoma.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 213-213
Author(s):  
Sang Eun Yoon ◽  
Jung Hoon Kim ◽  
Joon Young Hur ◽  
Su Jin Lee ◽  
Jeeyun Lee ◽  
...  
Keyword(s):  
Lymph Nodes ◽  
Neuroendocrine Carcinoma ◽  
Primary Tumor ◽  
Medical Center ◽  
Progression Free Survival ◽  
Complete Response ◽  
Tumor Site ◽  
Primary Tumor Site ◽  
Significant Difference ◽  
The Impact

213 Background: Gastroenteropancreatic neuroendocrine carcinoma (GEP-NEC) is a heterogeneous disease in terms of embryonic origin, aggressiveness, prognosis, and genomic profiling. Data regarding the efficacy of etoposide and cisplatin (EP) as a standard treatment of the primary tumor site in GEP-NEC are limited. Methods: We analyzed 64 patients with histopathologically confirmed metastatic GEP-NEC who received EP at Samsung Medical Center, Seoul, Korea, between January 2010 and January 2018. Based on primary tumor site, outcome of treatment with EP was evaluated. Results: Primary sites included 22 foregut-derived GEP-NECs (stomach, n = 6; duodenum, n = 4; pancreas, n = 12), 4 midgut-derived GEP-NECs, 5 hindgut-derived GEP-NECs of the rectum, 25 GEP-NECs originating from the hepatobiliary (HB) tract, and 12 GEP-NECs involving only intra-abdominal lymph nodes. No patient had a complete response (CR) and 17 had a partial response (PR), resulting in a 27.9% response rate (RR). When evaluating the efficacy of EP based on primary tumor site, the RR was most favorable in GEP-NECs involving only intra-abdominal lymph nodes, followed by GEP-NECs originating from foregut, midgut, HB, and hindgut. However, no statistically significant difference was observed for RR based on primary tumor site (p = 0.821). Similarly, no significant differences were found for progression-free survival (PFS) among patients with GEP-NECs arising from various primary tumor sites. Conclusions: Results from this study showed thatRR and PFS associated with EP treatment were not different based on the primary tumor site in patients with advanced or metastatic GEP-NEC.

A randomized controlled phase III multicenter study on dose escalation in definitive chemoradiation for patients with locally advanced esophageal cancer: ARTDECO study.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 281-281 ◽  
Author(s):  
Maarten C.C.M. Hulshof ◽  
Debby Geijsen ◽  
Tom Rozema ◽  
Vera Oppedijk ◽  
Jeroen Buijsen ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Radiation Dose ◽  
Lymph Nodes ◽  
Local Control ◽  
Dose Escalation ◽  
Primary Tumor ◽  
Progression Free Survival ◽  
Locoregional Control ◽  
Free Survival ◽  
Definitive Chemoradiation

281 Background: To analyze the effect of radiation dose escalation to the primary tumor on local control, locoregional control, survival and toxicity in definitive chemoradiation for esophageal cancer. Methods: Patients with clinical stage T2-4, N0-3, M0 carcinoma of the esophagus were randomized between a standard dose of 50.4 Gy/1.8 Gy/5,5 weeks to the tumor and regional lymph nodes (SD) versus the same dose combined with an integrated boost of 0,4 Gy per fraction (total 61,6 Gy) to the primary tumor (HD). Chemotherapy consisted of 6 weekly concurrent carboplatin (AUC 2) and paclitaxel (50 mg/m2) in both arms. The primary endpoint was local progression free survival (LPFS) and 260 patients were needed to detect a difference of 15% (power: 80%). Secondary endpoints were locoregional progression free survival (LRPFS), overall survival (OS) and toxicity. Patients were stratified for histological subtype. Results: Between September 2012 and June 2018, 260 patients were included. Reasons for inoperability were proximal localization and patient preference (44%), comorbidity (30%), unresectable lymph nodes (11%), T4 (5%), local recurrence 2% and combinations (7%). 61% of the patients had a squamous cell carcinoma (SCC) and 39% had an adenocarcinoma (AC). 94% completed radiation treatment and 85% had at least 5 courses chemotherapy. Median follow up time was 45 months. 3-year LPFS was 70% in the SD arm versus 76% in the HD arm (ns). LPFS for SCC and AC was 74% versus 81% and 62% versus 65% for SD and HD, resp. (ns). 3-year LRPFS was 53% and 63% for the SD and HD arm resp. (p = 0.08). 1 year any progression free survival was 60% for SCC and 50% for AC, without a significant difference between SD and HD (p = 0,5). 3-year OS was 41% versus 40% for SD and HD resp. Overall grade 4 and 5 CTC toxicity was 12% and 4% in the SD arm versus 14% and 10% in the HD arm, resp. Conclusions: In definitive chemoradiation for esophageal cancer, radiation dose escalation up to 61,6 Gy to the primary tumor did not result in a significant increase in local control over 50,4 Gy. Numerical improvement of locoregional control after HD was observed with an increase in toxicity and without improving OS. Clinical trial information: NL38343.018.11.

DREAMM-9: Phase III study of belantamab mafodotin plus VRd versus VRd alone in transplant-ineligible newly diagnosed multiple myeloma (TI NDMM).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. TPS8556-TPS8556 ◽  
Author(s):  
Saad Zafar Usmani ◽  
Evangelos Terpos ◽  
Wojt Janowski ◽  
Hang Quach ◽  
Sarah West ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Residual Disease ◽  
Single Agent ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Complete Response ◽  
Phase Iii ◽  
Clinical Activity ◽  
Efficacy And Safety ◽  
Open Label

TPS8556 Background: Bortezomib, lenalidomide, and dexamethasone (VRd) is the standard of care for transplant-eligible and TI NDMM, but relapse is usually inevitable. The median progression-free survival (PFS) is ~3 years for patients with TI NDMM, and with each relapse, the duration of response (DoR) diminishes, highlighting the need for novel, effective, targeted agents. Single-agent belantamab mafodotin is a first-in-class B-cell maturation antigen–binding, humanized, afucosylated, monoclonal immunoconjugate, showing deep and durable responses in heavily pretreated patients with relapsed/refractory multiple myeloma ( Lancet Oncol2020). Preclinical work suggests belantamab mafodotin plus bortezomib or lenalidomide enhances anti-myeloma activity. Therefore, studying clinical activity of belantamab mafodotin in combination with these agents is warranted. Methods: DREAMM-9 (NCT04091126) is a two-part, open-label study to determine efficacy and safety of single-agent belantamab mafodotin with VRd vs. VRd alone in patients with TI NDMM. Patients aged ≥18 years with ECOG status 0–2 and adequate organ system functions will be eligible. Part 1 (dose selection) will evaluate safety/tolerability of belantamab mafodotin with VRd administered by single (Day 1) or split dosing (Days 1 and 8) in ≤5 cohorts (n = 12/cohort): 1.9 mg/kg, 2.5 mg/kg split and single, and 3.4 mg/kg split and single. Six more patients may be added to cohort(s) most likely to be selected as recommended Phase III dose (RP3D). Dose-limiting toxicities and adverse events (AEs) will be assessed, and belantamab mafodotin RP3D determined through modified toxicity probability interval criteria. Part 2 (randomized Phase III) will determine efficacy and safety of belantamab mafodotin at RP3D with VRd vs. VRd alone (n = 750) in two arms randomized 1:1. Dual primary endpoints will be rate of minimal residual disease (MRD) negativity and PFS. Secondary endpoints will be response rates (overall response, complete response, very good partial response or better, sustained MRD negativity), DoR, time to progression, and overall survival. Safety assessment will include AEs, serious AEs and ocular findings. In both parts, belantamab mafodotin will be given with VRd for eight induction cycles and then with Rd for maintenance until disease progression or unacceptable toxicity. Funding: GlaxoSmithKline (209664). Drug linker technology licensed from Seattle Genetics; monoclonal antibody produced using POTELLIGENT Technology licensed from BioWa. Clinical trial information: NCT04091126 .

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