Early results of TROPHY-U-01 Cohort 2: Sacituzumab govitecan (SG) in platinum-ineligible patients (pts) with metastatic urothelial cancer (mUC) who progressed after prior checkpoint inhibitor (CPI) therapy.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 5027-5027 ◽  
Author(s):  
Daniel Peter Petrylak ◽  
Scott T. Tagawa ◽  
Rohit K. Jain ◽  
Manojkumar Bupathi ◽  
Arjun Vasant Balar ◽  
...  
Keyword(s):  
Safety Profile ◽  
Phase 1 ◽  
Primary Objective ◽  
First Line ◽  
Antibody Drug Conjugate ◽  
Open Label ◽  
Early Results ◽  
Metastatic Urothelial Cancer ◽  
Metastatic Setting ◽  
Grade 3

5027 Background: SG is an antibody-drug conjugate consisting of a humanized monoclonal anti–Trop-2 antibody coupled to the cytotoxic agent, SN-38, via a unique hydrolyzable linker. The epithelial cell surface antigen, Trop-2, demonstrates greater expression between UC vs normal tissue, and is a promising target. In a phase 1/2 basket study (IMMU-132-01), SG showed an overall response rate (ORR) of 31% and manageable toxicity in 45 pts with mUC who had a median of 2 (range 1–6) prior therapy lines (Tagawa 2019 ASCO GU). Recent interim results for cohort 1 of the TROPHY-U-01 study in 35 pts with mUC who progressed on platinum and CPI therapy demonstrated an ORR of 29% in pts with a median of 3 prior treatment lines (range 2–6) (Tagawa 2019 ESMO). The most common grade ≥3 treatment-related AE (TRAE) was neutropenia. Methods: TROPHY-U-01 (NCT03547973) is a global, open-label, phase 2 trial evaluating the antitumor activity of SG (10 mg/kg, days 1 and 8 of 21-day cycles) in pts with advanced UC with measurable disease and ECOG PS 0 or 1. Cohort 2 includes platinum-ineligible pts who progressed after CPI therapy in the first-line metastatic setting. The primary objective is ORR evaluated with RECISTv1.1 by central review. Secondary objectives include progression-free survival, overall survival, and duration of response. Results: 18 pts with baseline tumor assessment (50% male; median age 79 y [range 57–87], 67% visceral metastases; 28% liver metastases) received a median of 2 (range 1–5) prior therapies. At a median follow-up of 6 months, ORR was 28% (5/18) with 4 confirmed PRs, and 1 PR pending confirmation. The majority of pts (61% [11/18]) had target lesion reduction. The safety profile was consistent with prior reports. Key grade ≥3 TRAEs were neutropenia (39%), fatigue (33%), diarrhea (28%), leukopenia (22%), anemia (17%), and febrile neutropenia (11%). No events of interstitial lung disease, ocular toxicities, or grade > 2 neuropathy were reported. There were no treatment-related deaths. Conclusions: In cisplatin-ineligible pts, the ORR for currently approved first-line CPI treatments is ~23–29% (Balar 2017 Lancet; Vuky 2018 ASCO). These preliminary data with SG show a manageable safety profile with an encouraging ORR of 28% and support the development of SG in platinum-ineligible pts with mUC who have progressed after CPI therapy. Clinical trial information: NCT03547973 .

Safety and clinical activity of durvalumab monotherapy in patients with hepatocellular carcinoma (HCC).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 4071-4071 ◽  
Author(s):  
Zev A. Wainberg ◽  
Neil Howard Segal ◽  
Dirk Jaeger ◽  
Kyung-Hun Lee ◽  
John Marshall ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Safety Profile ◽  
Phase 1 ◽  
Primary Objective ◽  
Clinical Activity ◽  
Open Label ◽  
Sorafenib Treatment ◽  
Secondary Objective ◽  
Pugh Class ◽  
Grade 3

4071 Background: Durvalumab, an anti-PD-L1 mAb, has shown early and durable clinical activity with manageable safety in an ongoing Phase 1/2, multicenter, open-label study in pts with advanced solid tumors. Interim analyses from the HCC cohort in the dose-expansion part of this study are reported here. Methods: Patients with HCC (Child-Pugh class A) received durvalumab 10 mg/kg i.v. q2w for 12 months or until confirmed progressive disease, whichever occurred first. The primary objective was to evaluate the safety profile; secondary objective was to assess the antitumor activity (investigator-assessed RECIST v1.1). Clinical activity was evaluated for the total HCC population and by viral status. Results: As of Oct 24 2016, 40 HCC pts with median 23.9 (range 2.4–34.7) weeks follow-up received durvalumab. 93% had prior sorafenib. Treatment-related AEs occurred in 80.0% of pts, most commonly fatigue (27.5%), pruritus (25.0%) and elevated aspartate aminotransferase (AST) (22.5%). Grade 3–4 treatment-related AEs were reported in 20.0% of pts, most commonly elevated AST (7.5%) and elevated alanine aminotransferase (5.0%). 7 (17.5%) pts completed the initial 12-month treatment and 7 (17.5%) pts discontinued treatment because of an AE (none related to treatment). There were no deaths due to treatment-related AEs. Clinical activity is presented in the table. 4 pts achieved a PR; 2 were ongoing at data cut-off. Conclusions: Durvalumab had an acceptable safety profile and showed promising antitumor activity and OS in pts with HCC, particularly HCV+ pts. Clinical trial information: NCT01693562. [Table: see text]

A phase I, open-label, multicenter, single-dose escalation and multi-dose study of a monoclonal antibody targeting CEACAM1 in subjects with selected advanced or recurrent malignancies.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 3094-3094
Author(s):  
Roni Shapira ◽  
Jeffrey S. Weber ◽  
Ravit Geva ◽  
Mario Sznol ◽  
Harriet M. Kluger ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Drug Disposition ◽  
Phase 1 ◽  
Primary Objective ◽  
Immune Checkpoints ◽  
Open Label ◽  
Trial Testing ◽  
Dose Study ◽  
Cea Gene ◽  
Grade 3

3094 Background: The carcinomembryonic antigen cell adhesion molecule 1 (CEACAM1, CD66a) is a member of the CEA gene family. CEACAM1 interacts homophilically and heterophilically with CEACAM5, and is involved in various anti-proliferative activities. CEACAM1 is expressed on a variety of epithelial and hematological cells, including multiple types of cancer and activated lymphocytes. High CEACAM1 expression in some tumor types is known to be associated with poor disease prognosis. Recently it was demonstrated CEACAM1 is co-expressed on exhausted lymphocytes with other immune checkpoints such as TIM-3 and may regulate downstream activity. CM24 is a novel humanized α-CEACAM1-specific antibody with nM affinity to the N terminal domain of CEACAM1, which blocks intercellular CEACAM1 interactions. Methods: The primary objective was to test the safety and tolerability of CM24 in adult patients with advanced or recurrent cancer. Secondary objectives included assessment of CM24 PK and PD profiles, anti-tumor response and the recommended Phase 2 dose. Patient received IV infusion of CM24 at 7 dose levels ranging between 0.01 and 10 mg/kg in a cycle of 4 doses administered q2wks followed by a 6-week observation only period and additional 6 cycles. Results: 27 patients (median pretreatment of 4 prior regimens; range 2-8, 11 colorectal, 7 melanoma, 4 ovarian, 3 gastric, 2 NSCLC; 13 males, 14 females, mean age of 60 years), were included. Treatment with CM-24 was overall well-tolerated without DLTs up to 10 mg/kg. The most frequent AE was grade 1-3 increased alanine aminotransferase (7 subjects) and the most severe AE was grade 3/4 increase in gamma-glutamyltransferase (4 subjects). Drug-related AEs were observed in 63% of the subjects with grade 3-5 occurred in 3.7%. Eight subjects (29.6%) had stable disease as the best overall response. Median overall survival was 4 (3.4, 8.0) and 6.2 (2.7, 10.2) months for the 3 and 10 mg/kg doses, suggesting dose response. Cmax, AUC and t1/2 increased with increasing dose with the longest t1/2 of 11.2 days obtained at 10mg/kg. The average target occupancy of CM24 at 3mg/kg and 10mg/kg were 75% and 93%, respectively. Conclusions: PK and target-mediated drug disposition analysis suggest that doses higher than 10mg/kg are needed for target saturation at a q2 week regimen while a q3 week regimen is less optimal. A phase 1/2 clinical trial testing CM24 in combination with anti-PD-1 therapy in patients with NSCLC including assessment of CEACAM1 expression is warranted. Clinical trial information: NCT02346955 .

Early safety from a phase 1, multicenter, open-label clinical trial of talimogene laherparepvec (T-VEC) injected into liver tumors.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 438-438 ◽  
Author(s):  
J. Randolph Hecht ◽  
Miklos Pless ◽  
Antonio Cubillo ◽  
Aitana Calvo ◽  
Steven Raman ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Liver Tumors ◽  
Disease Incidence ◽  
Phase 1 ◽  
Cell Cancer ◽  
Maximum Tolerated Dose ◽  
Primary Objective ◽  
Open Label ◽  
Dose Escalation Study ◽  
Grade 3

438 Background: T-VEC is a genetically modified HSV-1 oncolytic immunotherapy designed to preferentially replicate in tumors, produce GM-CSF, and stimulate anti-tumor immune responses. This study evaluates the safety of intrahepatic injection (inj) of T-VEC in patients (pts) with hepatocellular carcinoma (HCC) or liver metastases (mets). Methods: The primary objective is to assess the maximum tolerated dose. Eligible pts were ≥ 18 years (y) old, had progressive HCC or breast cancer (BC), colorectal cancer (CRC), gastroesophageal cancer, melanoma, non-small cell lung cancer, or renal cell cancer with liver mets, with measurable liver tumors suitable for inj. This dose escalation study comprised 2 groups: A (non-HCC) and B (HCC). T-VEC was given initially at 106 plaque-forming units (PFU)/mL followed by up to 4 mL of 107 PFU/mL (cohort 1) or 108 PFU/mL (cohort 2) every 21 (±3) days (Q21D), or up to 8 mL of the maximum tolerated concentration (MTC) Q21D (cohort 3). Inj volume was based on lesion size. Results: Results from cohorts 1 and 2 of group A are reported. 14 pts were treated; 12 (3 BC, 9 CRC) were DLT-evaluable: Median age was 65.5 y (range: 33, 73); median number of inj was 3; 1 pt received all 12 inj. MTC was 108 PFU/mL. There was 1 DLT, grade 3 aspartate aminotransferase (AST)/grade 2 bilirubin increase (inc), after 1 dose. In all treated pts, 4 (28.6%) had grade 3/4 treatment-related adverse events (TRAEs): anemia and inc gamma-glutamyltransferase, alanine aminotransferase (ALT), and AST. There were 2 deaths attributable to disease. Incidence of serious AEs (SAEs) is shown (Table). Conclusions: The MTC was 108 PFU/mL Q21D after initial inj at 106 PFU/mL. Repeated intrahepatic inj of T-VEC at the FDA-approved concentration for intralesional inj of melanoma was deemed tolerable and feasible in pts with liver mets. Additional investigation in combination with a PD-1 inhibitor is planned. Clinical trial information: NCT02509507. [Table: see text]

EV-201: Results of enfortumab vedotin monotherapy for locally advanced or metastatic urothelial cancer previously treated with platinum and immune checkpoint inhibitors.

2019 ◽  
Vol 37 (18_suppl) ◽  
pp. 4505-4505 ◽  
Author(s):  
Daniel Peter Petrylak ◽  
Arjun Vasant Balar ◽  
Peter H. O'Donnell ◽  
Bradley Alexander McGregor ◽  
Elisabeth I. Heath ◽  
...  
Keyword(s):  
Urothelial Cancer ◽  
Checkpoint Inhibitors ◽  
Phase 1 ◽  
Locally Advanced ◽  
Unmet Need ◽  
Antibody Drug Conjugate ◽  
Open Label ◽  
Metastatic Urothelial Cancer ◽  
Duration Of Response ◽  
Previously Treated

4505 Background: Locally advanced or metastatic urothelial cancer (la/mUC) remains a lethal disease with limited treatment options for patients (pts) who progress on or after platinum and/or checkpoint inhibitor (CPI). Enfortumab vedotin (EV) is an antibody-drug conjugate targeting Nectin-4, which is highly expressed in UC. EV-201 is a pivotal, single-arm, two-cohort study of EV in la/mUC patients with prior CPI and platinum-containing chemotherapy (Cohort 1) or a CPI and no prior chemotherapy (Cohort 2). Here, we present preliminary data from Cohort 1. Methods: Pts in this open-label, multicenter study received 1.25 mg/kg EV on Days 1, 8, and 15 of each 28-day cycle. The primary endpoint was confirmed ORR per RECIST 1.1 by blinded independent central review. Secondary endpoints are duration of response, PFS, OS, safety/tolerability. Results: Between Oct 2017 and Jul 2018, EV-201 enrolled 128 pts in Cohort 1 (la/mUC pts previously treated with platinum and a CPI), 125 of whom were treated with EV (70% male; median age 69 y [range 40–84 y]; 34% upper tract; a median of 2 prior systemic therapies). As of 03 Jan 2019, the confirmed ORR was 42% (95% CI: 33.6%–51.6%), with 9% CR. The ORR in CPI non-responders was 38% (95% CI: 27.3%–49.2%), and 36% (95% CI: 22.9%–50.8%) in pts with liver metastases (LM). Most common treatment-related AEs, as determined by investigators, included fatigue (50%), alopecia (48%), and decreased appetite (41%). Treatment-related AEs of interest include any rash (48% all grade, 11% ≥ G3) and any peripheral neuropathy (50% all grade, 3% ≥ G3). One death was reported as treatment related by the investigator (interstitial lung disease), but was confounded by a suspected pulmonary infection. Conclusions: Preliminary results from this EV pivotal study demonstrated a clinically meaningful ORR, consistent with the phase 1 trial, in la/mUC pts with prior platinum and CPI, including LM pts, where there is a high unmet need. EV was well tolerated with a manageable safety profile in these pts. Updated data, including duration of response, PFS, and OS will be presented. Clinical trial information: NCT03219333.

A phase I study of enfortumab vedotin (ASG-22CE; ASG-22ME): Updated analysis of patients with metastatic urothelial cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 106-106 ◽  
Author(s):  
Daniel Peter Petrylak ◽  
Raymond P. Perez ◽  
Jingsong Zhang ◽  
David C. Smith ◽  
Joseph D. Ruether ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Phase I ◽  
Phase I Study ◽  
Urothelial Cancer ◽  
Dose Range ◽  
Tolerability Profile ◽  
Antibody Drug Conjugate ◽  
Metastatic Urothelial Cancer ◽  
Metastatic Setting ◽  
Grade 3

106 Background: Enfortumab vedotin, an antibody–drug conjugate, delivers monomethyl auristatin E to tumors expressing Nectin-4, which is overexpressed in metastatic urothelial cancer (mUC). Methods: This Phase I study (NCT02091999) enrolled patients (pts) with solid tumors, including pts with mUC, treated with ≥1 prior chemotherapy regimen. All pts received different dose levels of IV enfortumab vedotin (0.5, 0.75, 1, 1.25 mg/kg) once weekly for 3 out of 4 wks. Nectin-4 expression was determined by IHC on archival tumor specimens and quantified by histochemical scoring (H-score). Primary endpoint was tolerability; secondary endpoint was antitumor activity assessed every 8 wks per RECIST v1.1. Results: As of 3 Jan 2017, 68 pts with mUC (46 M/22 F; median age, 67 yr [range: 41–84]) had been treated. Of these, 62% received ≥2 prior therapies in the metastatic setting and 40% had prior immune checkpoint inhibitor (CPI) therapy. In these pts, Nectin-4 expression was high and prevalent (median H-score, 280 [range: 32–300]). Treatment-related adverse events (TRAEs) were reported in 58 pts (85%); diarrhea, fatigue, nausea, and pruritus were TRAEs reported in ≥25% of pts. Most TRAEs were grade ≤2 in severity; 19 pts (28%) experienced a TRAE of grade ≥3. The most common grade ≥3 AEs (occurring in ≥5 pts), regardless of attribution to treatment, were urinary tract infection (10%) and hypophosphatemia (9%). No treatment-related deaths have occurred. Sixty pts had ≥1 post-baseline assessment. Antitumor activity was observed across the dose range; overall response rate (ORR) was 40% (95% CI: 27.6–53.5) for all evaluable pts (n = 60), 46% (95% CI: 25.6–67.2) in pts with prior CPI exposure (n = 24), and 44% (95% CI: 19.8–70.1) in pts with metastasis to the liver (n = 16). Complete responses were noted in 3 pts at doses ≥1 mg/kg. Median treatment duration was 26 wks (range: 5.1–64.6), median duration of response was 18 wks (95% CI: 8.4–40.1), and median progression-free survival was 17 wks (95% CI: 15.1–23.3). Study enrollment is ongoing. Conclusions: Enfortumab vedotin demonstrated a favorable tolerability profile with encouraging antitumor activity in heavily pretreated mUC, including pts for whom CPIs have failed. Clinical trial information: NCT02091999.

First-line durvalumab + monalizumab, mFOLFOX6, and bevacizumab or cetuximab for metastatic microsatellite-stable colorectal cancer (MSS-CRC).

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 128-128
Author(s):  
Zev A. Wainberg ◽  
Jennifer Robinson Diamond ◽  
Giuseppe Curigliano ◽  
Sanjeev Deva ◽  
Johanna C. Bendell ◽  
...  
Keyword(s):  
Peripheral Neuropathy ◽  
Phase 1 ◽  
Objective Response ◽  
Biologic Agent ◽  
First Line ◽  
Open Label ◽  
Duration Of Response ◽  
Secondary Endpoints ◽  
Grade 3 ◽  
Ecog Ps

128 Background: Targeting multiple immune checkpoint pathways and combining checkpoint inhibition with chemotherapy may enhance response in MSS-CRC. In a Phase 1/2, multicenter, open-label study, the anti-PD-L1 antibody durvalumab (D) was added to monalizumab (M; an anti-NKG2A antibody). In dose-exploration cohorts, D+M was added to chemotherapy and a biologic agent (bevacizumab [DMCB] or cetuximab [DMCC]) for first-line treatment of advanced/metastatic MSS-CRC. Initial data showed DMCB was well tolerated and clinically active. Here we report updated efficacy and safety of DMCB and initial safety of DMCC. Methods: Eligible patients (pts) had MSS-CRC ( RAS/BRAF wt with a left-sided colon primary tumor in the DMCC cohort) and ECOG PS 0–1. They received D 1500 mg Q4W, M 750 mg Q2W, mFOLFOX6 Q2W and bevacizumab 5 mg/kg Q2W or cetuximab 250/400 mg/m2 QW (up to 500 mg/m2 Q2W) for up to 3 yr. The primary endpoint was safety and tolerability; secondary endpoints included antitumor activity. Results: As of Aug 26, 2019, 18 pts received DMCB and 17 pts received DMCC. Treatment-emergent adverse events (AEs) occurred in 100.0% of the DMCB cohort (most commonly fatigue, nausea and peripheral neuropathy) and 94.1% of the DMCC cohort (most commonly peripheral neuropathy, rash and dermatitis acneiform). The AEs were grade 3/4 in 77.8% of pts receiving DMCB and 70.6% of pts receiving DMCC, and were serious in 38.9% and 47.1%, respectively. Response was evaluable in 17 pts receiving DMCB; objective response rate was 41.2% (all PRs; Table). Responses occurred early and the median duration of response has not yet been reached. Conclusions: In advanced/metastatic MSS-CRC, first-line DMCB and DMCC had a manageable safety profile and DMCB showed promising preliminary activity. Clinical trial information: NCT02671435. [Table: see text]

Phase IV study of first-line bevacizumab plus irinotecan and infusional 5-FU/LV in patients with metastatic colorectal cancer: AVIRI

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 4068-4068 ◽  
Author(s):  
A. F. Sobrero ◽  
S. Young ◽  
M. Balcewicz ◽  
S. Chiarra ◽  
R. Perez Carrion ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Safety Profile ◽  
Overall Response Rate ◽  
Response Rate ◽  
Primary Objective ◽  
Phase Iii ◽  
First Line ◽  
Open Label ◽  
Overall Response

4068 Background: Bevacizumab (BEV) is a monoclonal antibody that inhibits tumour angiogenesis by targeting VEGF. In a phase III trial (AVF2107g), BEV significantly improved overall (OS) and progression-free survival (PFS) when combined with first-line irinotecan plus bolus 5-fluorouracil (5-FU)/leucovorin (LV) (IFL) in patients with metastatic colorectal cancer (mCRC). A multicentre, open-label trial is being conducted to evaluate the efficacy and safety of first-line BEV in combination with irinotecan and infusional 5-FU (FOLFIRI), a widely used first-line chemotherapy (CT) regimen. Methods: Patients had to have: mCRC; no surgery within 28 days; no prior CT for metastatic disease; ECOG PS 0/1, adequate organ function; no CNS metastases. CT consisted of a minimum of six cycles of irinotecan plus infusional 5-FU/LV according to the classical FOLFIRI regimen; variations like the simplified FOLFIRI and the weekly regimen were also allowed. BEV 5mg/kg was given on day 1 with CT and then every 2 weeks until disease progression. Tumour assessments were performed every 3 months during the first 12 months and every 4 months thereafter. Safety was assessed at the time of CT administration and every 4 weeks thereafter. The primary objective was PFS; secondary objectives included safety, overall response rate, time to response, duration of response and OS. Results: A total of 209 patients were enrolled at 31 centres worldwide, between April and November 2005. An interim analysis showed that the safety profile of BEV plus FOLFIRI appeared to be similar to that reported for Avastin plus IFL. The 44% overall response rate and 90% disease control rate are at least equivalent to that reported in comparable trials. Additionally, the 6 months PFS estimate of 82% was superior to that reported in AVF2107. Mature PFS data will be presented. Conclusions: AVIRI is the largest clinical trial, to date, to report data for BEV in combination with FOLFIRI in first-line patients with mCRC. The safety profile appears consistent with that observed in other BEV trials in mCRC, while the preliminary efficacy data suggest that this regimen is as active as the bolus regimen. No significant financial relationships to disclose.

Safety and quality of life (QoL) findings from a randomized phase III study of capecitabine (X) + oxaliplatin (O) (XELOX) vs. infusional 5-FU/LV + O (FOLFOX-6) in metastatic colorectal cancer (MCRC)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 4099-4099 ◽  
Author(s):  
M. Hebbar ◽  
J. Bennouna ◽  
V. Boige ◽  
M. Ychou ◽  
G. Lledo ◽  
...  
Keyword(s):  
Safety Profile ◽  
Compliance Rate ◽  
Progression Free Survival ◽  
Primary Objective ◽  
Phase Iii ◽  
Final Visit ◽  
First Line ◽  
Best Response ◽  
Grade 3 ◽  
Eortc Qlq

4099 Background: A recent phase III trial in first-line MCRC showed that XELOX is non-inferior to infusional 5-FU + oxaliplatin (FOLFOX-4) for progression-free survival (PFS) [Cassidy ESMO 2006]. Here we present safety and QoL findings from a study of XELOX vs. FOLFOX-6 in first-line MCRC. Methods: Between 16 May 03 and 31 Aug 04, 306 patients (pts) were randomized to receive either XELOX (156 pts: × 1,000mg/m2 bid d1–14, O 130mg/m2 d1, q3w) or FOLFOX-6 (150 pts: O 100mg/m2 d1 LV 400mg/m2 2h infusion then 5-FU 400mg/m2 i.v. bolus then 2,400–3,000mg/m2 46h infusion, q2w) for 6 months. Primary objective: demonstrate non inferiority of XELOX in terms of best response rate (RECIST). Secondary objectives: evaluate QoL and pt satisfaction with care by EORTC QLQ-C30 and FACIT (chemotherapy convenience and satisfaction) questionnaires. Pts completed questionnaires at baseline, before cycles 3/4, 6/8 and at final visit in XELOX/FOLFOX-6 arms, respectively. Results: 245 pts (QLQ-C30) and 225 pts (satisfaction) were evaluable for QoL. The compliance rate was >70%. At baseline, QoL scores were not significantly different. QLQ-C30 functional and symptomatic scores were stable in both arms. According to FACIT, there was no difference between arms, although XELOX-treated pts wasted less hours of their free time than those on FOLFOX-6: 10±23 vs. 37±68 hours, respectively (p=0.007). XELOX was a more ‘comfortable’ treatment (p<0.001 vs. FOLFOX-6 at 2nd evaluation and p=0.009 at 3rd evaluation). Safety profile was acceptable in both arms. In the safety population (n=304), XELOX pts had more grade 3/4 hand-foot syndrome (3 vs. 1% p=0.215), thrombocytopenia (12 vs. 5% p=0.052) and diarrhea (12% vs. 7% p=0.1), but less grade 3/4 febrile neutropenia (0 vs. 6% p=0.001) and neuropathy (8 vs. 19% p=0.003) than those on FOLFOX-6. Treatment discontinuation for toxicity was 19% and 23% for XELOX and FOLFOX-6 arms, respectively. Conclusions: XELOX is comparable to FOLFOX-6 in terms of QoL with less time wasted receiving XELOX. XELOX is also non-inferior to FOLFOX-6 (primary endpoint met/presented at same meeting) with a similar safety profile in first-line MCRC. No significant financial relationships to disclose.

An open-label study of rovalpituzumab tesirine in patients with DLL3-expressing advanced solid tumors.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. TPS2597-TPS2597 ◽  
Author(s):  
Edward Kavalerchik ◽  
Satwant Lally ◽  
Tae H. Han ◽  
Laura R. Saunders ◽  
Sheila Bheddah ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Dose Escalation ◽  
Solid Tumor ◽  
Phase 1 ◽  
Large Cell ◽  
Maximum Tolerated Dose ◽  
Primary Objective ◽  
Notch Receptor ◽  
Antibody Drug Conjugate ◽  
Open Label

TPS2597 Background: Delta-like protein 3 (DLL3) is an inhibitory ligand of the Notch receptor family. It is highly expressed in high-grade neuroendocrine carcinoma (NEC), such as small cell lung cancer (SCLC) and large cell NEC (LCNEC), but is not expressed in normal tissue. DLL3 is expressed in melanoma, glioblastoma (GBM), neuroendocrine prostate, medullary thyroid carcinoma (MTC), and other solid cancers. Rovalpituzumab tesirine (Rova-T™) is an antibody-drug conjugate targeting DLL3, composed of a DLL3-specific IgG1 monoclonal antibody joined to a toxic DNA cross-linking agent by a cleavable linker. Rova-T binds to DLL3 on target-expressing cells, is internalized and cleaved, releasing the toxin to induce cell death. A Phase 1 study of Rova-T in SCLC showed encouraging antitumor activity in DLL3-high patients (pts), and was well-tolerated (Rudin et al., Lancet Oncol, 2016). As novel therapies are needed for multiple cancers that express DLL3, Rova-T may be effective in these tumors. Methods: This is a Phase 1/2, open-label, multicenter study (NCT02709889) with 8 cohorts of pts (up to ~318 total, 14 pts enrolled as of 20 January 2017) with melanoma, MTC, GBM, LCNEC, neuroendocrine prostate cancer, gastroenteropancreatic NEC, other NEC, or other solid tumor. In Part A, a 3+3 dose escalation will be used. Rova-T 0.2, 0.3, or 0.4 mg/kg will be given on Day 1 of each 42-day cycle. Dose-limiting toxicities (DLTs) will be assessed over a 21-day period. Dose escalation will proceed within cohort until a maximum tolerated dose is reached. Part B expansion, Stage 1, will explore the recommended dose in 7 pts in disease specific cohorts. Stage 2 will use an adaptive 2-stage design to determine sample size. Pt eligibility: ≥ 18 years; histologically confirmed, measurable, advanced solid tumor; relapsed/refractory to prior standard therapy; ECOG 0-1; no prior exposure to a pyrrolobenzodiazepine-based drug. Primary objective: assess safety and tolerability of Rova-T. Secondary objectives: explore Rova-T antitumor activity, pharmacokinetics, and incidence of anti-therapeutic antibodies. Exploratory objectives: explore the relationship between DLL3 and clinical outcome, and effects on biomarkers and pharmacodynamics. Clinical trial information: NCT02709889.

Mature results from EV-101: A phase I study of enfortumab vedotin in patients with metastatic urothelial cancer (mUC).

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 377-377 ◽  
Author(s):  
Jonathan E. Rosenberg ◽  
Srikala S. Sridhar ◽  
Jingsong Zhang ◽  
David C. Smith ◽  
Joseph D. Ruether ◽  
...  
Keyword(s):  
Survival Data ◽  
Urinary Tract Obstruction ◽  
Single Agent ◽  
Primary Objective ◽  
Antibody Drug Conjugate ◽  
Primary Tumor Site ◽  
Metastatic Urothelial Cancer ◽  
Duration Of Response ◽  
Grade 3

377 Background: Enfortumab vedotin (EV) is an antibody–drug conjugate that delivers MMAE, a microtubule disrupting agent, to tumors expressing Nectin-4, a protein found on most urothelial cancers. Preliminary results of the EV-101 study (NCT02091999) suggest EV is active and tolerable. Methods: Patients with mUC treated with ≥1 prior chemotherapy, or those ineligible for cisplatin, received EV 1.25 mg/kg on Day 1, 8, and 15 every 28 day cycle. The primary objective was tolerability; antitumor activity (ORR per RECIST v1.1), assessed every 8 wk, was a secondary objective. Results: As of14 Sept 2018,112 pts with mUC received EV with a median follow up of 13.4 mo. Bladder was the primary tumor site in 86 pts (77%) and 33 (29.5%) had liver metastases (LM). Nearly all pts received prior platinum chemotherapy; 89 (79.5%) received prior anti-PD(L)1. EV was well tolerated; fatigue (53%), alopecia (46%), and decreased appetite (42%) were the most commonly reported treatment-related AEs (TRAEs). Anemia (8%), hyponatremia (7%), UTI (7%), and hyperglycemia (6%) were the grade ≥3 AEs reported in ≥5% of pts regardless of attribution; 4 fatal TRAEs were reported (respiratory failure, urinary tract obstruction, diabetic ketoacidosis, multi-organ failure). Confirmed ORR was 42% (CR, n = 5; PR, n = 42). Among responders, median duration of response was 7.7 mo (95% CI 5.6, 9.6) and 23.4% of responses were ongoing with a median follow up of 11.3 mo. Estimated median PFS and OS were 5.4 mo (95% CI 5.1, 6.3) and 12.5 mo (95% CI 9.3, 16.1), respectively; OS at 1 yr was 51.8%. Similar results were seen in pts with prior anti-PD(L)1 and with LM (Table). Conclusions: Single-agent EV was generally well tolerated and provided encouraging response and survival data in a population with an unmet medical need including pts with LM, which is associated with poor prognosis. Phase 2 and 3 monotherapy studies as well as evaluation of combination therapies are ongoing. Clinical trial information: NCT02091999. [Table: see text]

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