An open-label, single-arm, multicenter, phase II study of RC48-ADC to evaluate the efficacy and safety of subjects with HER2 overexpressing locally advanced or metastatic urothelial cancer (RC48-C009).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 4584-4584
Author(s):  
Xinan Sheng ◽  
Zhisong He ◽  
Weiqing Han ◽  
Ai-Ping Zhou ◽  
Hong Luo ◽  
...  
Keyword(s):  
Phase Ii ◽  
Urothelial Cancer ◽  
Phase Ii Study ◽  
Objective Response ◽  
Locally Advanced ◽  
Active Agent ◽  
Visceral Metastasis ◽  
Open Label ◽  
Medical Needs ◽  
Metastatic Urothelial Cancer

4584 Background: There is still urgent medical needs in the patients with locally advanced or metastatic urothelial cancer (mUC) post to the failure of at least one line chemotherapy. RC48-ADC, a novel humanized anti-HER2 antibody-drug conjugate (ADC), has proved its efficacy in these patients (RC48-C005, NCT03507166), most of whom had received gemcitabine and platinum. Taking into consideration that taxane is another possible active agent for mUC, this study aims to further evaluate the efficacy of RC48-ADC in HER2 overexpressing mUC post to the failure of platinum, gemcitabine and taxane. Methods: This study was an open-label, multicenter, single-arm, non-randomized phase II study. Eligibility criteria included: histologically confirmed UC, HER2 overexpressing (IHC 2+ or 3+), ECOG PS 0-1, failed platinum, gemcitabine and taxane. The patients received RC48-ADC treatment alone (2 mg/kg IV infusion, q2w) until disease progression, unacceptable toxicity, withdrawal, death or study termination. The primary endpoint was objective response rate (ORR) assessed by blinded independent review committee (BIRC) according to RECIST v1.1. Progress-free survival (PFS), duration of response (DOR), overall survival (OS), and safety was also assessed. Results: Patient enrollment for this study started in December 2018 and completed in September 2020. A total of 64 patients were enrolled, with a median age of 62.5 years. At baseline, most patients (82.8%) had visceral metastasis. Fifty-five patients (85.9%) had received ≥ 2 lines treatment and 19 (29.7%) patients had prior immune checkpoint inhibitor (CPI) therapy. As of Nov 30, 2020, the confirmed ORR assessed by BIRC was 46.9% (95% CI: 34.3%, 59.8%) and the median DOR was 8.3 months (95% CI: 4.3, NE), the median PFS was 4.3 months (95% CI: 4.0, 6.8). The median OS was 14.8 months (95% CI: 8.7, 21.1). The ORR was 60.0% (15/25) in patients with HER2 IHC3+ or FISH test positive, 45.3% (24/53) in patients with visceral metastasis, 42.1% (8/19) in patients post to CPI therapy. The ORR was 55.6% (5/9), 50.0% (21/20) and 30.8% (4/13), in patients who had received 1 line, 2 lines and ≥ 3 lines treatment, respectively. Most commonly reported TRAEs were leukopenia (45.3%), AST increase (43.8%), neutropenia (42.2%), hypoesthesia (42.2%), ALT increase (37.5%) and fatigue (35.9%); Most commonly reported ≥ grade 3 TRAEs were neutropenia (9.4%) and hypoesthesia (6.3%) Conclusions: In patients with HER2 overexpressing (IHC 2+ or 3+) mUC who had failed platinum, gemcitabine and taxane, and the great majority of whom had received ≥2 prior lines treatment, RC48-ADC has demonstrated consistently excellent efficacy and benefit-risk profile compared with the RC48-C005 study which enrolled patients with mUC who had received ≥1 line prior chemotherapy. Clinical trial information: NCT03809013.

A randomized noncomparative phase II study of maintenance therapy with multiepitope vaccine Tedopi (OSE2101) ± nivolumab or FOLFIRI after induction chemotherapy (CT) with FOLFIRINOX in patients (Pts) with advanced pancreatic ductal adenocarcinoma (aPDAC) (TEDOPaM–PRODIGE 63 GERCOR D17-01 study).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. TPS4160-TPS4160
Author(s):  
Cindy Neuzillet ◽  
Vincent Hautefeuille ◽  
Aurélien Lambert ◽  
Marie-Line Garcia-Larnicol ◽  
Dewi Vernerey
Keyword(s):  
Maintenance Therapy ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Performance Status ◽  
Objective Response ◽  
Locally Advanced ◽  
Vaccine Antigen ◽  
New Combination ◽  
Ductal Adenocarcinoma ◽  
Open Label

TPS4160 Background: FOLFIRINOX (5-fluorouracil [5FU], folinic acid [FA], irinotecan [Iri], and oxaliplatin [Ox]) is a standard 1st-line treatment in fit Pts with aPDAC. Anti-PD-1/PD-L1 as single agents have failed in PDAC so far and new combination immunotherapies are needed. Tedopi (OSE2101) is a multiple neoepitope vaccine restricted to HLA-A2 positive Pts, targeting 5 tumor-associated antigens (CEA, HER2, MAGE2, MAGE3, TP53) that are frequently expressed in PDAC. This study aims to assess the efficacy and safety of Tedopi alone and in combination with anti-PD-1 nivolumab, or FOLFIRI as maintenance therapy in Pts with aPDAC after FOLFIRINOX induction CT. Methods: TEDOPaM - PRODIGE 63 is a 3-arm, Fleming 2-stage, open-label, randomized, non-comparative phase II study. 156 Pts with locally advanced or metastatic, pathologically proven PDAC; ECOG performance status 0-1; HLA-A2 genotype; controlled disease (objective response or stable disease) after 8 cycles of (modified) FOLFIRINOX; and adequate organ functions, are randomized (1:1:1, stratified on center, tumor stage, and best response to FOLFIRINOX) into 3 arms: Clinical trial information: NCT03806309. In Arms B and C, FOLFIRI is reintroduced at disease progression or unacceptable toxicity. Primary endpoint: overall survival rate at M12. Secondary endpoints: progression-free survival (CT-scan Q8W), duration of disease control, safety, objective response rate, RECIST v1.1/iRECIST comparison, HRQoL (EORTC QLQ-C30), Q-TWiST. An interim analysis is planned after inclusion of 20 Pts in each arm. Translational research will be performed on tumor tissue (initial FFPE biopsy and optional re-biopsy at inclusion): RNAseq (cancer and stroma), mutation burden, MMR status, immune infiltrates; and in blood (before and on-treatment): cytokine panel, PBMC phenotyping, vaccine-antigen specific T-cells, TCR repertoire, and extracellular vesicles, to explore biomarkers and pharmacodynamics effects of Tedopi ± nivolumab. Enrollment (12th Feb 2019): 1. ClinicalTrials Registration: NCT03806309.[Table: see text]

scholarly journals PIVOT-10: Phase II study of bempegaldesleukin plus nivolumab in cisplatin-ineligible advanced urothelial cancer

2020 ◽  
Author(s):  
Robert A Huddart ◽  
Arlene O Siefker-Radtke ◽  
Arjun V Balar ◽  
Mehmet A Bilen ◽  
Thomas Powles ◽  
...  
Keyword(s):  
Phase Ii ◽  
Urothelial Cancer ◽  
Objective Response ◽  
Locally Advanced ◽  
Response Rates ◽  
Complete Response ◽  
First Line ◽  
First Line Therapy ◽  
Programmed Death ◽  
Metastatic Urothelial Cancer

The choice of first-line therapy for patients with metastatic urothelial cancer (mUC) is based on cisplatin-eligibility and programmed death-ligand 1 (PD-L1) status. For patients with mUC who are ineligible for cisplatin and with low PD-L1 expression, chemotherapy-based regimens are the only approved first-line option. In a Phase I/II trial of the chemotherapy-free regimen, bempegaldesleukin (BEMPEG; NKTR-214) plus nivolumab, patients with locally advanced or mUC experienced tumor responses regardless of baseline PD-L1 expression (objective response rates: 50 and 45% in patients with PD-L1-positive and -negative tumors, respectively). The Phase II PIVOT-10 study (NCT03785925), evaluates efficacy and safety of first-line BEMPEG plus nivolumab in cisplatin-ineligible patients with locally advanced or mUC. Most patients will have low PD-L1 expression. Primary end point: objective response rates (including complete response).

A phase II study of RC48-ADC in HER2-positive patients with locally advanced or metastatic urothelial carcinoma.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 4509-4509 ◽  
Author(s):  
Xinan Sheng ◽  
Ai-Ping Zhou ◽  
Xin Yao ◽  
Yanxia Shi ◽  
Hong Luo ◽  
...  
Keyword(s):  
Urothelial Carcinoma ◽  
Phase Ii ◽  
Objective Response Rate ◽  
Response Rate ◽  
Phase Ii Study ◽  
Objective Response ◽  
Locally Advanced ◽  
Visceral Metastasis ◽  
Her2 Positive ◽  
Metastatic Urothelial Carcinoma

4509 Background: Urothelial carcinoma (UC) is the third largest cancer type with HER2 positive cancer. RC48-ADC is a novel humanized anti-HER2 antibody-drug conjugate (ADC). This study was to evaluate the activity of RC48-ADC in HER2-positive patients with locally advanced or metastatic urothelial carcinoma (mUC). Methods: This study is an open-label, multicenter, single-arm, non-randomized phase II study. Eligibility criteria include: histologically confirmed UC, HER2-positive (IHC 2+ or 3+), ECOG PS 0-1, treated with ≥1 prior systemic treatment. The patients received RC48-ADC treatment alone (2 mg/kg IV infusion, q2w) until disease progression, unacceptable toxicity, withdrawal, or study termination. The primary endpoint was objective response rate (ORR). Progress-free survival (PFS), overall survival (OS), and safety was also assessed. Results: Patient enrollment for this study was completed in November 2018. A total of 43 patients were enrolled, with a median age of 64 years old. At baseline, most patients (37/43) had visceral metastasis. Fourteen (32.6%) patients had received ≥ 2 lines treatment and 8 (18.6%) patients had prior immune checkpoint inhibitor (CPI) therapy in second line treatment. The objective response rate was 60.5% (95% CI: 44.4%, 75.0%) and the DCR was 90.7% (39/43). As of Jan 23, 2019, the median PFS for the overall study population was not yet reached, and the median PFS was 7.8 months (95% CI: 4.9, 10.7) for the 9 patients who started RC48-ADC prior to Jun 30, 2018. The ORR was 70.6% (12/17) in patients with HER2 FISH+ or IHC3+. The ORR was 64.9% (24/37) in patients with visceral metastasis and was 70.0% (14/20) in liver metastasis patients especially. The ORR was 64.3% in patients post to ≥ 2 lines treatment and 75.0% in patients post to immunotherapy. Common treatment-related AEs were leukopenia (51.2%), hypoesthesia (41.9%), alopecia (41.9%), neutropenia (37.2%), fatigue (34.9%), ALT increase (32.6%), and AST increase (32.6%); Most were Grade 1 or 2. Conclusions: RC48-ADC has demonstrated a clinically meaningful ORR of 60.5% in pretreated HER-2 positive mUC patients including those who underwent failure to the immunotherapy. Clinical trial information: NCT03507166.

TROPHY-u-01: A phase II open-label study of sacituzumab govitecan (IMMU-132) in patients with advanced urothelial cancer after progression on platinum-based chemotherapy and/or anti-PD-1/PD-L1 checkpoint inhibitor therapy.

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. TPS495-TPS495 ◽  
Author(s):  
Scott T. Tagawa ◽  
Daniel Peter Petrylak ◽  
Petros Grivas ◽  
Neeraj Agarwal ◽  
Cora N. Sternberg ◽  
...  
Keyword(s):  
Urothelial Cancer ◽  
Checkpoint Inhibitor ◽  
Objective Response ◽  
Locally Advanced ◽  
Low Grade ◽  
Phase 2 ◽  
Open Label ◽  
Phase 2 Trial ◽  
Metastatic Urothelial Cancer ◽  
Platinum Based Chemotherapy

TPS495 Background: Patients (pts) with unresectable locally advanced or metastatic urothelial cancer (mUC) who progress after platinum-based chemotherapy and checkpoint inhibitor (CPI) therapy and pts ineligible for platinum-based chemotherapy who progress after CPI have limited treatment options and poor outcomes. Trop-2 is an epithelial cell surface antigen that is overexpressed in UC. Sacituzumab govitecan (SG) is a novel antibody-drug conjugate that targets Trop-2 and delivers the active metabolite (SN38) of the topoisomerase I inhibitor irinotecan to tumor cells. In a phase 1/2 single-arm trial, pts with advanced cancers received SG 10 mg/kg intravenously on days 1 and 8 of a 21-day cycle; preliminary results in the cohort of 41 evaluable pts with mUC and a median of 3 (range 1–6) prior therapies showed an objective response rate (ORR) of 34%. Adverse events (AE) were mostly low grade, including diarrhea (63%), nausea (56%), and fatigue (49%). Neutropenia (all grades) occurred in 49% of pts (≥ grade 3/4, 39%; treatment-related serious AE of febrile neutropenia, 5%). Median overall survival was 16.1 months, and median progression-free survival was 7.1 months. These results warrant further investigation in a dedicated phase 2 trial. Methods: TROPHY-U-01 is a single-arm, open-label, global phase 2 trial evaluating the antitumor activity and safety of SG in 140 pts with advanced UC. The primary cohort (progression after platinum chemotherapy and CPI) will enroll 100 pts in a Simon 2-stage design with > 90% power accounting for dropouts to exclude the null hypothesis or ORR < 12%, while a second cohort (40 pts) will comprise cisplatin-ineligible pts who received prior CPI. The primary objective is ORR per RECIST 1.1, assessed by central review. Secondary objectives include response duration, PFS, OS, and safety/tolerability. Enrollment began in August 2018. Clinical trial information: NCT03547973.

Phase II study of the combination of abemaciclib and pembrolizumab in locally advanced unresectable or metastatic gastroesophageal adenocarcinoma: Big Ten Cancer Research Consortium BTCRC-GI18-149.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. TPS461-TPS461
Author(s):  
Nataliya Volodymyrivna Uboha ◽  
Jens C. Eickhoff ◽  
Chandrikha Chandrasekharan ◽  
Shadia Ibrahim Jalal ◽  
Al Bowen Benson ◽  
...  
Keyword(s):  
Phase Ii ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Phase Ii Study ◽  
Checkpoint Inhibitors ◽  
Objective Response ◽  
Locally Advanced ◽  
Open Label ◽  
Significance Level ◽  
Gastroesophageal Adenocarcinoma

TPS461 Background: Metastatic gastroesophageal adenocarcinoma (GEA) has poor prognosis. Overall survival (OS) remains around 12 months (mo) with current therapies. Pembrolizumab is approved for advanced GEA that has progressed on at least 2 prior lines of systemic therapy. However, the majority of patients progress on this treatment, and less than 15% of patients experience objective response (OR). This study will evaluate efficacy of pembrolizumab in combination with cyclin-dependent kinase 4/6 (CDK4/6) inhibitor, abemaciclib, in patients with advanced GEA. Preclinical studies have demonstrated that CDK4/6 inhibitors can increase anti-tumor immunity and can synergize with immune checkpoint inhibitors. Based on these data, we hypothesize that abemaciclib will augment response to pembrolizumab in GEA. Methods: This is a multi-institutional, single arm, open label, phase II study of abemaciclib in combination with pembrolizumab in patients with advanced GEA who have progressed or were intolerant to at least 2 prior lines of therapy. Patients previously treated with immune checkpoint inhibitors or with microsattelite unstable tumors will be excluded. Treatments will be given on a 21 day cycle until disease progression or intolerable toxicities. Pembrolizumab, 200 mg intravenously, will be given on day 1, and abemaciclib, 150 mg, will be taken orally twice a day on days 1-21. Primary endpoint is progression free survival (PFS). Secondary endpoints include PFS rate at 6 mo, disease control rate, OS and OR rate. Correlative endpoints will examine relationship between PDL1 status, genomic signature and treatment response. Saliva samples will be collected for microbiome analysis. Archival tumor tissue and blood samples will be banked for future studies. A total of 31 evaluable subjects will be enrolled to detect an anticipated increase in the median PFS from 2 months (null hypothesis) to 4 months with 80% power at the one-sided 0.05 significance level. The trial is open to enrollment. Clinical trial information: NCT03997448.

scholarly journals Pembrolizumab versus chemotherapy in recurrent, advanced urothelial cancer in Japanese patients: a subgroup analysis of the phase 3 KEYNOTE-045 trial

2019 ◽  
Vol 25 (1) ◽  
pp. 165-174 ◽  
Author(s):  
Hiroyuki Nishiyama ◽  
Yoshiaki Yamamoto ◽  
Naoto Sassa ◽  
Kazuo Nishimura ◽  
Kiyohide Fujimoto ◽  
...  
Keyword(s):  
Urothelial Cancer ◽  
Objective Response ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Japanese Patients ◽  
Open Label ◽  
End Points ◽  
Free Survival ◽  
Metastatic Urothelial Cancer ◽  
Grade 3

Abstract Background The open-label, randomized, active-controlled KEYNOTE-045 study (NCT02256436) showed that second-line pembrolizumab significantly improved overall survival (OS) of patients with advanced/metastatic urothelial cancer (UC) that progressed after first-line platinum-containing chemotherapy, compared with standard chemotherapy (paclitaxel, docetaxel, or vinflunine). Pembrolizumab is approved for patients with bladder cancer in Japan. Patients and methods Analysis was performed in the subgroup of Japanese patients enrolled in the KEYNOTE-045 study. Coprimary end points were OS and progression-free survival (PFS). Objective response rate (ORR) and safety were secondary end points. Results Fifty-two Japanese patients (pembrolizumab, n = 30; chemotherapy, n = 22) were followed up for a median of 26.1 months. Patients who received pembrolizumab compared with chemotherapy had a 19% lower risk for death (hazard ratio [HR] 0.81, 95% CI 0.44–1.50); after adjusting for baseline covariates, the HR for OS was 0.61 (95% CI 0.32–1.15). The 24-month OS rate was higher with pembrolizumab (26.9% vs 14.3%). PFS was 2.0 and 4.9 months for pembrolizumab and chemotherapy, respectively (HR 1.71, 95% CI 0.95–3.08). ORR was similar for pembrolizumab and chemotherapy (20.0% vs 18.2%); durability of response was higher with pembrolizumab: 67% and 33% of patients, respectively, maintained a response for > 12 months. Treatment-related adverse events, including grade 3–5 events, occurred less frequently with pembrolizumab. Conclusions Pembrolizumab provided durable antitumor activity in patients with locally advanced/metastatic UC that progressed after platinum-containing chemotherapy in the overall population and in the Japanese subgroup; safety profile was consistent with that previously observed for pembrolizumab.

A phase II study of IMGN242 (huC242-DM4) in patients with CanAg-positive gastric or gastroesophageal (GE) junction cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e15625-e15625 ◽  
Author(s):  
L. W. Goff ◽  
K. Papadopoulos ◽  
J. A. Posey ◽  
A. T. Phan ◽  
A. Patnaik ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Study ◽  
Objective Response ◽  
Locally Advanced ◽  
Study Drug ◽  
Maximum Tolerated Dose ◽  
Preliminary Evidence ◽  
Open Label ◽  
Prior Therapy ◽  
Dosing Strategy

e15625 Background: IMGN242 is a conjugate of the cytotoxic maytansinoid DM4 and the monoclonal antibody huC242, which binds to CanAg. In a Phase I study, the maximum tolerated dose for IMGN242 was determined to be 168 mg/m2, with ocular changes the primary dose-limiting toxicity. This Phase II study was initiated to assess IMGN242 for the treatment of gastric cancer. Methods: In this open-label, multi-center study, IMGN242 is given as a single IV infusion every three weeks to patients with CanAg-expressing metastatic or locally-advanced gastric or GE junction cancer. Patients must have been treated with at least one prior therapy to qualify for enrollment. The study has a 2-step design: If ≥1 objective response is achieved among the first 23 patients (Step 1), a total of 39 response-evaluable patients will be enrolled (Step 2). Results: Overall, 9 patients have received IMGN242. The first 6 were treated with 168 mg/m2, and 1 of these patients showed a marked biologic response by the FDG-PET scan in Cycle 1 followed by an unconfirmed partial response based on CT scan in Cycle 2. However, 3 of these 6 patients developed ocular toxicities assessed to be study drug related. Only patients with low plasma CanAg levels (<1000 U/ml) developed ocular toxicities, and clinical pharmacokinetic and pharmacodynamic (PK/PD) analyses revealed that plasma CanAg affects study drug exposures. The study was amended to differentiate the IMGN242 doses (126 mg/m2 or 168 mg/m2) administered based on the patient's plasma CanAg levels (< or >1000 U/mL). To date, 3 patients have received IMGN242 with this dosing strategy and no ocular toxicities have been reported. Conclusions: IMGN242 showed preliminary evidence of activity in this patient population. A novel Phase II dosing strategy is being used that should enhance tolerability. Patient enrollment is ongoing and updated results will be reported. [Table: see text]

EV-201 study: A single-arm, open-label, multicenter study of enfortumab vedotin for treatment of patients with locally advanced or metastatic urothelial cancer who previously received immune checkpoint inhibitor therapy.

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. TPS542-TPS542
Author(s):  
Jonathan E. Rosenberg ◽  
Elisabeth I. Heath ◽  
Peter H. O'Donnell ◽  
Noah M. Hahn ◽  
Arjun Vasant Balar ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Immune Checkpoint ◽  
Urothelial Cancer ◽  
Objective Response ◽  
Locally Advanced ◽  
Transitional Cell ◽  
Tolerability Profile ◽  
Phase 2 ◽  
Open Label ◽  
Metastatic Urothelial Cancer

TPS542 Background: The majority of patients with locally advanced or metastatic urothelial cancer (la/mUC) will not respond to immune checkpoint inhibitors (CPIs) given in the post-platinum or cisplatin ineligible setting, and there are currently no approved standard therapies after disease progression. Enfortumab vedotin (EV), an antibody-drug conjugate, delivers the microtubule-disrupting agent monomethyl auristatin E to tumors expressing Nectin-4, which is overexpressed in mUC. Preliminary results from an ongoing phase 1 study of EV monotherapy in pts with mUC (Petrylak ASCO 2017) showed that EV was well tolerated in pts with mUC. Nausea (36%), pruritus (31%), and fatigue (30%) were the most commonly reported treatment-related AEs. The most common grade ≥3 AEs (regardless of attribution) were urinary tract infection (11%) and hypophosphatemia (9%). EV showed an objective response rate (ORR) of 41% (29 out of 71 pts) across all dose levels and 53% (16 out of 30 pts) ORR at the recommended phase 2 dose of 1.25 mg/kg. The ORR was not diminished in pts with prior CPI use (44%), prior taxane use (41%) or in pts with liver metastases (47%). These encouraging results along with a favorable safety and tolerability profile warrant further investigation of EV as a monotherapy. Methods: This single-arm, open label, multicenter phase 2 study (NCT03219333) evaluates the antitumor activity and safety of EV monotherapy in ~120 pts with la/mUC. Pts must have previously received a CPI and either have received prior platinum or be ineligible for cisplatin. Pts must have histologically or cytologically documented transitional cell carcinoma of the urothelium that progressed during or following receipt of most recent therapy. The primary objective is to determine antitumor activity of EV as measured by ORR. Secondary objectives include assessment of duration of response, disease control rate, PFS, OS, and safety/tolerability of EV. Pts must have tumor tissue available for exploratory analyses. Response is assessed per RECIST v1.1. Study enrollment began in Sept 2017. Clinical trial information: NCT03219333.

A phase II study of RC48-ADC in HER2-negative patients with locally advanced or metastatic urothelial carcinoma.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e17113-e17113 ◽  
Author(s):  
Huayan Xu ◽  
Xinan Sheng ◽  
Xieqiao Yan ◽  
Zhihong Chi ◽  
Chuanliang Cui ◽  
...  
Keyword(s):  
Urothelial Carcinoma ◽  
Phase Ii ◽  
Objective Response ◽  
Locally Advanced ◽  
Good Effect ◽  
Visceral Metastasis ◽  
Antibody Drug Conjugate ◽  
Her2 Positive ◽  
Open Label ◽  
Metastatic Urothelial Carcinoma

e17113 Background: RC48-ADC is a novel humanized anti-HER2 antibody-drug conjugate (ADC). A phase II clinical study showed that RC48-ADC has a good effect on locally advanced or metastatic urothelial carcinoma with HER2-positive expression that failed standard chemotherapy. In the study, some patients with HER2-postive immunohistochemistry (IHC 2+) but negative FISH test still benefit from the treatment of RC48-ADC.The study was to evaluate the activity and safety of RC48-ADC in HER2-negative patients with locally advanced or metastatic urothelial carcinoma. Methods: This study is an open-label, single-center, one-arm, non-randomized phase II trial. Eligibility criteria include: histologically confirmed urothelial carcinoma, HER2-negasitive (IHC 0 or 1+), ECOG PS 0-1, treated with ≥1 prior systemic treatment. The patients received RC48-ADC treatment alone (2mg/kg IV infusion, q2w) until disease progression, unacceptable toxicity, withdrawal, or study termination. The primary objectives were activity (ORR) and safety. Progress-free survival, disease control rate and overall survival will also be assessed. Results: As of February 2020, 8 patients were enrolled in the study. The median age was 65 years old. At baseline, most patients (6/8) had visceral metastasis. 6 (75%) patients had received≥2 lines treatment and 4 (50%) patients had prior immune checkpoint inhibitor (CPI) therapy in second line treatment. The objective response rate was 25% (2/8) and the DCR was 75% (6/8). The ORR was 33.3% (2/6) in patients with visceral metastasis and was 50.0% (2/4) in liver metastasis patients. The ORR was 33.3% (2/6) in patients post to ≥ 2 lines of treatment and 25% (1/4) in patients post to immunotherapy. Common treatment-related AEs were AST increase (62.5%), ALT increase (50.0%), nausea (50.0%), leukopenia (37.5%), fatigue (37.5%), vomiting (37.5%), hypoesthesia (25.0%), alopecia (25.0%), and neutropenia (25.0%). Most of these AE were Grade 1 or 2. The AE of Grade 3 was neutropenia (12.5%). The SAE was CPK increased (12.5%). Conclusions: The study showed that RC48-ADC was safety and the ORR was 25% in HER-negative patients with locally advanced or metastatic urothelial carcinoma. Clinical trial information: NCT04073602.

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