EV-301: Phase III study to evaluate enfortumab vedotin (EV) versus chemotherapy in patients with previously treated locally advanced or metastatic urothelial cancer (la/mUC).

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. TPS497-TPS497 ◽  
Author(s):  
Daniel Peter Petrylak ◽  
Jonathan E. Rosenberg ◽  
Ignacio Duran ◽  
Yohann Loriot ◽  
Guru Sonpavde ◽  
...  
Keyword(s):  
Disease Progression ◽  
Response Rate ◽  
Checkpoint Inhibitors ◽  
Single Agent ◽  
Objective Response ◽  
Locally Advanced ◽  
Phase Iii ◽  
Survival Duration ◽  
Metastatic Urothelial Cancer ◽  
Platinum Based Chemotherapy

TPS497 Background: Standard first-line treatment for patients (pts) with la/mUC is cisplatin-based chemotherapy or carboplatin-based chemotherapy for pts unfit for cisplatin. Immune checkpoint inhibitors (CPIs) are standard treatment options for pts who progressed during or after platinum-based chemotherapy. While some pts with la/mUC achieve durable responses with CPIs, less than 25% of pts respond. Following failure of a CPI, no therapies are approved. Enfortumab vedotin is a fully humanized monoclonal antibody that delivers the microtubule-disrupting agent monomethyl auristatin E to tumors expressing Nectin-4, which is expressed in 97% of mUC pt samples (Petrylak et al. ASCO, 2017). In a phase 1 study (EV-101; NCT02091999), single-agent EV 1.25 mg/kg was generally well tolerated and demonstrated a confirmed objective response rate (ORR) of 42% across the overall population of pts with mUC; in pts with prior CPI therapy or liver metastasis at baseline confirmed ORRs of 42% and 36% were observed. A pivotal phase 2 study of EV in la/mUC pts with prior CPI treatment (EV-201; NCT03219333) is ongoing. Methods: EV-301 is a global, multicenter, open-label phase 3 trial (NCT03474107) enrolling adult pts with la/mUC and an ECOG performance status score ≤1, who have received a prior platinum-containing chemotherapy, and have experienced disease progression during or following treatment with a CPI. Approximately 550 pts will be randomized (1:1) to receive EV (1.25 mg/kg) administered by IV infusion over approximately 30 minutes on Days 1, 8, and 15 of each 28-day cycle ( Arm A), or investigator choice of IV docetaxel, paclitaxel, or vinflunine (EU only) on Day 1 of each 21-day cycle ( Arm B). Treatment with the study drug will continue until radiological disease progression, intolerance, or other discontinuation criterion is met. Radiological assessments of tumor response status will be performed at baseline and every 8 weeks. The primary endpoint is overall survival; secondary endpoints include progression-free survival, duration of response, and overall response rate, as well as assessment of safety/tolerability, and quality-of-life parameters. Clinical trial information: NCT02091999.

Preliminary results from a phase II study of nivolumab for patients with metastatic adrenocortical carcinoma (ACC).

2017 ◽  
Vol 35 (7_suppl) ◽  
pp. 96-96 ◽  
Author(s):  
Ludimila Cavalcante ◽  
Benedito A. Carneiro ◽  
Ricardo Lima Barros Costa ◽  
Young Kwang Chae ◽  
Alfred Rademaker ◽  
...  
Keyword(s):  
Disease Progression ◽  
Phase Ii ◽  
Response Rate ◽  
Phase Ii Study ◽  
Checkpoint Inhibitors ◽  
Treatment Options ◽  
Objective Response ◽  
Locally Advanced ◽  
Fixed Dose ◽  
Initial Report

96 Background: ACC is an exceedingly rare malignancy with an estimated incidence of 0.7 cases per million per year. Patients presenting with metastatic disease have an estimated 5-year survival rate of < 15%, without effective standard treatment options. Immunotherapy approaches such as checkpoint inhibitors have emerged as effective therapies for multiple malignancies. Nivolumab, a monoclonal IgG4 antibody against the programmed death-1 (PD-1) receptor on T-cells, acts by inhibiting the interaction with PD-L1 and PD-L2 and thus eliciting an increased anti-tumor immune response. This phase II study will assess the efficacy of nivolumab monotherapy according to objective response rate (ORR) in patients with advanced ACC – the study is currently in the patient enrollment phase. Methods: Patients with metastatic or locally advanced ACC with disease progression after treatment with ≥ 1 line of therapy (including mitotane and/or chemotherapy), or not eligible for first-line chemotherapy are currently being enrolled on this phase II study. Nivolumab is given at a fixed dose of 240mg IV q2 weeks until confirmed disease progression, unacceptable toxicity, or withdrawal. Planned accrual of up to 33 patients will follow a Simon two stage design with interim analysis for efficacy after 10 evaluable patients are enrolled. Results: This is an initial report of the first 7 evaluable patients enrolled on study. Median age 57 years; female (4/7); endocrine hyperfunction (2/7); prior chemotherapy with EDP +/- mitotane (5/7). Patients were treated with a median of 4 doses of nivolumab. Median time to progression of 8 weeks. Best overall response rate thus far has been progression of disease in 5 pts, with 2 pts pending evaluation. Grade 3 or 4 adverse events (AEs) at least possibly related to nivolumab: tremor, hypokalemia (1 pt each). Reported grade 1 and 2 AEs: LFT elevation (3 pts), lower extremity edema (2 pts), lymphopenia, urinary frequency and fatigue (1 pt each). Conclusions: Nivolumab has been well tolerated in this population of patients with metastatic ACC. Clinical trial information: NCT02720484.

Rucaparib for recurrent, locally advanced, or metastatic urothelial carcinoma (mUC): Results from ATLAS, a phase II open-label trial.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 440-440 ◽  
Author(s):  
Petros Grivas ◽  
Yohann Loriot ◽  
Susan Feyerabend ◽  
Rafael Morales-Barrera ◽  
Min Yuen Teo ◽  
...  
Keyword(s):  
Checkpoint Inhibitors ◽  
Parp Inhibitor ◽  
Single Agent ◽  
Objective Response ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Clinical Activity ◽  
Open Label ◽  
Platinum Based Chemotherapy ◽  
Previously Treated

440 Background: ATLAS (NCT03397394) evaluated the efficacy/safety of the PARP inhibitor (PARPi) rucaparib in patients (pts) with previously treated locally advanced/unresectable UC or mUC. Methods: Pts with measurable disease who had progressed after 1–2 prior regimens (ie, platinum-based chemotherapy [PBC] and/or immune checkpoint inhibitors [ICI]) were enrolled regardless of tumor homologous recombination deficiency (HRD) status. Prior PARPi was not allowed. Pts received rucaparib 600 mg PO BID. Baseline tumor tissue or archival tissue ≤6 mo without intervening therapy was required; serial circulating tumor DNA samples were collected. Primary endpoint was investigator-assessed objective response rate (RECIST v1.1) in the intent-to-treat and HRD-positive (defined as genomic loss of heterozygosity ≥10%) populations. Key secondary endpoints: progression-free survival (PFS) and safety. Clinical benefit rate (CBR) was defined as complete or partial response or stable disease (SD) lasting ≥16 weeks. Results: As of Oct 7, 2019, 97 pts were enrolled (median age 66 y [range, 39–87]); most were men (n=76, 78.4%) and had ECOG PS 1 (n=65, 67.0%). Sixty-six pts (68.0%) had both prior PBC and ICI. Twenty pts (20.6%) were HRD-positive, 30 (30.9%) were HRD-negative and 47 (48.5%) had unknown HRD status; 4 pts had a deleterious BRCA1/2 alteration. Median time on treatment was 54 d (range, 2–224). There were no confirmed responses. Of 96 evaluable pts, 27 (28.1%) had a best response of SD; CBR was 12.5% and median PFS was 1.8 mo. No relationship was observed between HRD status and clinical activity. Treatment was discontinued by 93 pts (95.9%), mainly due to radiologic or clinical progression (73.1%). Most frequent any grade treatment-emergent (any cause) adverse events were asthenia/fatigue (n=56, 57.7%), nausea (n=40, 41.2%), and anemia (n=34, 35.1%). Conclusions: Single agent rucaparib did not show activity in pts with previously treated advanced UC and enrollment was suspended at the first interim analysis. The safety profile was consistent with that observed in pts with ovarian cancer. Next generation sequencing–based characterization of the genomic landscape of mUC will be presented. Clinical trial information: NCT03397394.

A phase III, randomized, open-label, multicenter, global study of first-line (1L) durvalumab in combination with standard of care (SoC) chemotherapy and durvalumab in combination with tremelimumab and soc chemotherapy versus soc chemotherapy alone in patients with unresectable locally advanced or metastatic urothelial cancer (UC).

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. TPS499-TPS499
Author(s):  
Matt D. Galsky ◽  
Andrea Necchi ◽  
Srikala S. Sridhar ◽  
Osamu Ogawa ◽  
Dario Ruscica ◽  
...  
Keyword(s):  
Performance Status ◽  
Objective Response ◽  
Locally Advanced ◽  
Transitional Cell ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Poor Performance Status ◽  
Open Label ◽  
Metastatic Urothelial Cancer ◽  
Platinum Based Chemotherapy

TPS499 Background: Despite high response rates to 1L SoC for locally advanced or metastatic UC chemotherapy (gemcitabine +cisplatin or gemcitabine + carboplatin for patients who are cisplatin-ineligible [poor performance status, impaired renal function, comorbidities]), most patients experience disease progression. Novel strategies like combining chemotherapy and immunotherapy offer hope for improving clinical outcomes. Durvalumab is a selective, high affinity, engineered human IgG1 mAb that blocks PD-L1 binding to PD-1 and CD80. Tremelimumab is a human IgG2 mAb directed against CTLA-4. The mechanisms of action of PD-1 and CTLA-4 are nonredundant, so targeting both checkpoint pathways may have additive or synergistic efficacy compared to monotherapy. Studies in other tumor types of platinum-based chemotherapy combined with checkpoint blockade have yielded improved efficacy with acceptable safety and support exploration of this approach for 1L locally advanced or metastatic UC. Methods: NILE is a randomized, open-label, multicenter, global trial that will enroll approximately 1265 patients who will be randomized (1:1:1) to durvalumab + SoC chemotherapy, durvalumab + tremelimumab + SoC chemotherapy, or SoC chemotherapy as 1L-line therapy in patients with histologically or cytologically documented, unresectable, locally advanced or metastatic transitional cell carcinoma of the urothelium. Primary endpoints are progression-free survival using blinded independent central review assessments per RECIST 1.1 and overall survival (OS). Secondary endpoints include objective response rate, OS at 24 months, proportion of patients alive and progression free at 12 months, duration of response, disease control rate, time from randomization to second progression, and HRQoL. Safety, pharmacokinetics, immunogenicity, and biomarkers will also be assessed. The study opened for enrollment in September 2018. Clinical trial information: NCT03682068.

A phase III, randomized, open label, multicenter, global study of first-line (1L) durvalumab in combination with standard of care (SOC) chemotherapy and durvalumab in combination with tremelimumab and SOC chemotherapy versus SOC chemotherapy alone in patients with unresectable locally advanced or metastatic urothelial cancer (UC).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. TPS4590-TPS4590
Author(s):  
Matt D. Galsky ◽  
Andrea Necchi ◽  
Srikala S. Sridhar ◽  
Osamu Ogawa ◽  
Natasha Angra ◽  
...  
Keyword(s):  
Performance Status ◽  
Objective Response ◽  
Locally Advanced ◽  
Transitional Cell ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Poor Performance Status ◽  
Open Label ◽  
Metastatic Urothelial Cancer ◽  
Platinum Based Chemotherapy

TPS4590 Background: Despite high response rates to 1L SoC for locally advanced or metastatic UC chemotherapy (gemcitabine + cisplatin or gemcitabine + carboplatin for patients who are cisplatin-ineligible [poor performance status, impaired renal function, comorbidities]), most patients experience disease progression. Novel strategies such as combining chemotherapy and immunotherapy offer hope for improving clinical outcomes. Durvalumab is a selective, high affinity, engineered human IgG1 mAb that blocks PD-L1 binding to PD-1 and CD80. Tremelimumab is a human IgG2 mAb directed against CTLA-4. The mechanisms of action of PD-1 and CTLA-4 are nonredundant, so targeting both checkpoint pathways may have additive or synergistic efficacy compared with monotherapy. Studies of platinum-based chemotherapy combined with checkpoint blockade in other tumor types have yielded improved efficacy with acceptable safety and support exploration of this approach for 1L locally advanced or metastatic UC. Methods: NILE (NCT03682068) is a randomized, open-label, multicenter, global trial that will enroll approximately 1265 patients with histologically or cytologically documented, unresectable, locally advanced, or metastatic transitional cell carcinoma of the urothelium. Patients will be randomized (1:1:1) to durvalumab + SoC chemotherapy, durvalumab + tremelimumab + SoC chemotherapy, or SoC chemotherapy as 1L therapy. Primary endpoints are progression-free survival using blinded independent central review assessments per RECIST 1.1 and overall survival (OS). Secondary endpoints include objective response rate, OS at 24 months, proportion of patients alive and progression free at 12 months, duration of response, disease control rate, time from randomization to second progression, and health-related quality of life. Safety, pharmacokinetics, immunogenicity, and biomarkers will also be assessed. The study opened for enrollment in September 2018. 2019 American Society of Clinical Oncology, Inc. Reused with permission. This abstract was accepted and previously presented at the 2019 Genitourinary Cancers Symposium. Clinical trial information: NCT03682068.

A phase Ib study of combination of avelumab and taxane-based chemotherapy in platinum refractory or ineligible metastatic urothelial cancer (AVETAX study).

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 487-487 ◽  
Author(s):  
Rohan Garje ◽  
Timothy Ginader ◽  
Douglas Earl Laux ◽  
Kenneth Gerard Nepple ◽  
Mohammed M. Milhem ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Checkpoint Inhibitors ◽  
Standard Dose ◽  
Objective Response ◽  
Locally Advanced ◽  
Phase 2 ◽  
Metastatic Urothelial Cancer ◽  
Platinum Based Chemotherapy ◽  
Phase 1B ◽  
Expansion Cohort

487 Background: Advanced bladder cancer is the most common malignancy of the urinary system with 5-year OS rates of 5-7%. Platinum based chemotherapy and checkpoint inhibitors are currently available treatment options but with limited benefit. We hypothesize that combining Avelumab (anti-PD-L1 immunotherapy) with Docetaxel is safe and will lead to cancer cell death releasing neoantigens with enhanced anti-tumor immune mediated cytotoxicity. Methods: This is a phase 1b, single arm, non-randomized, open label prospective clinical trial to evaluate the combination of Avelumab and Docetaxel in adult subjects with locally advanced or metastatic urothelial carcinoma with disease progression during or following platinum-containing chemotherapy, or within 12 months of neoadjuvant or adjuvant platinum-containing chemotherapy. It has two phases: Phase 1b dose de-escalation of docetaxel (Level 0: 75, Level -1: 60 or Level -2: 45 mg/m2) with standard dose avelumab (10 mg/kg) to establish phase 2 dose in the standard 3+3 design. In the dose expansion phase, the phase 2 dose of docetaxel with avelumab will be evaluated for efficacy. The combination therapy is administered every 3 weeks for 6 cycles and then avelumab alone is continued every 2 weeks. Primary endpoint is safety. Efficacy endpoints include objective response rate, progression free survival and overall survival. Results: At the cutoff date of 10/21/2019, 10 eligible patients were enrolled in the study. Only one of the six patients treated with level 0 dose of docetaxel had a dose limiting toxicity (neutropenic fever). Docetaxel at 75 mg/m2 along the avelumab was deemed safe for dose expansion cohort. Additional 4 patients were enrolled in the dose expansion cohort. Efficacy data is preliminary with 1 patient achieving CR, 2 pts had PR, 2 pts had SD, 1 pt PD and 4 pts are not yet evaluable. The most common Grade 3 or 4 AEs were febrile neutropenia, urinary tract infection and confusion. No treatment related deaths were noted. Conclusions: The combination of docetaxel in combination with avelumab is safe and the preliminary data showed promising efficacy, further data to be presented at the meeting. Clinical trial information: NCT03575013.

scholarly journals 363 Vactosertib and durvalumab as second or later line treatment for PD-L1 positive non-small cell lung cancer: interim result

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A388-A388
Author(s):  
Byoung Chul Cho ◽  
Ki Hyeong Lee ◽  
Ji-Youn Han ◽  
Byoung Yong Shim ◽  
Hye Ryun Kim ◽  
...  
Keyword(s):  
Immune Checkpoint ◽  
Objective Response Rate ◽  
Immune Checkpoint Inhibitors ◽  
Advanced Nsclc ◽  
Response Rate ◽  
Checkpoint Inhibitors ◽  
Objective Response ◽  
Platinum Based Chemotherapy ◽  
Number Of Patients ◽  
Anti Tumor Activity

BackgroundTargeting transforming growth factor-β (TGF-β) is reported to augment the efficacy of immune checkpoint inhibitors (ICIs) through either enhanced anti-tumor immunity or the correction of tumor microenvironment (TME). Therefore, the combination of vactosertib, a highly selective TGF-β RI kinase inhibitor, and durvalumab is anticipated to improve anti-tumor activity of the ICI. A phase 1b/2a study was conducted to evaluate the combination of vactosertib and durvalumab in patients with advanced NSCLC who progressed after platinum-based chemotherapy.MethodsPatients were treated with vactosertib at a dose of 200 mg twice daily (five days on and two days off) and durvalumab at a dose of 1500 mg every four weeks. Eligible patients were ≥19 years old with good performance status (ECOG 0–1) and have no prior exposure to immune checkpoint inhibitors or other TGF- β R1 kinase inhibitors. The objectives of this analysis were to evaluate the safety, antitumor activity including objective response rate (ORR), duration of response (DOR), and time to response (TTR) as well as circulating pharmacodynamic biomarkers related to TGF-β signaling. Response was assessed per RECIST (v1.1).ResultsBy August 4 2020, twenty-six PD-L1 positive (SP263 assay) patients were analyzed. Median age was 61.5 years (range 48–83), 69.2% were male, median number of previous lines of chemotherapy was 1 (range 1–4), and all patients were PD-L1 positive (15 patients with PD-L1≥25% and 11 patients with PD-L1 1–24%). The most frequently reported treatment-related adverse events (TRAE) were itching (38.5%) and skin rash (34.6%), but no Gr≥3 itching and rash were observed. Each case of the following was reported as Grade 3 TRAEs: adrenal insufficiency, anemia, and pneumonitis; Grade 4 TRAE, CPK increase, was observed in one patient. Objective response rate was 30.8% and 40.0% in patients with PD-L1≥1% and ≥25% respectively. Circulating PAI-1 and CTGF evaluated in 15 patients decreased significantly on Cycle 1 day 5. Ongoing biomarker results will be presented.ConclusionsThe combination of vactosertib and durvalumab has demonstrated a manageable safety profile and encouraging anti-tumor activity as a potential therapeutic strategy in patients with advanced NSCLC. The efficacy outcomes of this combination in a larger number of patients with advanced NSCLC will be followed.Trial RegistrationNCT03732274Ethics ApprovalThe study was approved by Ethics Board of Severance Hospital (4-2018-0892), National Cancer Center (NCC2019-0057), St. Vincent’s Hospital (VC19MDDF0205), and Chungbuk National University Hospital (2019-08-015).

Tailored immunotherapy approach with nivolumab in advanced transitional cell carcinoma (TITAN-TCC).

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 446-446
Author(s):  
Marc-Oliver Grimm ◽  
Bernd Schmitz-Dräger ◽  
Uwe Zimmermann ◽  
Barbara Grün ◽  
Gustavo Bruno Baretton ◽  
...  
Keyword(s):  
Immune Checkpoint ◽  
Response Rate ◽  
Checkpoint Inhibitors ◽  
Objective Response ◽  
Transitional Cell ◽  
Added Value ◽  
Phase Iii ◽  
First Line ◽  
Third Line

446 Background: Several PD-1 immune-checkpoint inhibitors including Nivolumab (Nivo) are approved in urothelial cancer. Recently, in the front line setting, improved activity of combined PD-L1 and CTLA4 immune-checkpoint inhibition has been reported and a phase III trial with Nivolumab + Ipilimumab (Nivo+Ipi) is ongoing. Here we report a response-based tailored approach starting treatment with Nivo monotherapy using Nivo+Ipi as immunotherapeutic “boost”. Methods: Between July 2017 and April 2019 86 patients were enrolled and treated according to protocol version 3 (cohort 1). Patients started with Nivo 240 mg Q2W induction. After 4 dosings and tumor assessment at week 8 (i) responders (PR/CR) to Nivo monotherapy continued with maintenance while (ii) patients with stable (SD) or progressive disease (PD) received 2 cycles Nivo3+Ipi1 followed by another 2 cycles Nivo1+Ipi3 if not responding. Median follow-up is 8.7 months. The primary endpoint is confirmed investigator-assessed objective response rate (ORR) per RECIST1.1. Secondary endpoints include activity of Nivo monotherapy at week 8, remission rate with Nivo+Ipi “boosts”, safety, overall survival and quality of life. Results: Of the patients 42, 39 and 5 were first, second and third line, respectively. Median age was 67 years (range 45-84), 61 patients (71 %) were male and 25 female. ORR with Nivo monotherapy at first assessment (week 8) was 29 % and 23 % in first and second/third line, respectively. Of the patients 41 received Nivo+Ipi “boosts” after week 8 while 12 received later “boosts”. Best overall response (BOR) rate with Nivo induction ± Nivo+Ipi “boosts” was 48 % and 27 % in first and second/third line, respectively. In first line 7/17 (41 %) patients receiving Nivo+Ipi after week 8 had an improved response compared to 2/24 (8.3 %) in second/third line. Of the patients who continued with Nivo maintenance after week 8 and received later “boosts” 2/12 (17 %) had a PR and 2/12 (17 %) improved to SD. Treatment-related AEs will be presented. Conclusions: TITAN–TCC explores a response-driven use of Nivo+Ipi as an immunotherapeutic “boost”. In first line, this significantly improved ORR compared to the expected response rate of Nivo monotherapy, providing further evidence to the added value of Ipi in combination with Nivo. Further follow-up is ongoing to characterize duration and depth of response. Clinical trial information: NCT03219775 . Research Sponsor: Bristol-Myers Squibb[Table: see text]

TROPiCS-04: Study of sacituzumab govitecan in metastatic or locally advanced unresectable urothelial cancer that has progressed after platinum and checkpoint inhibitor therapy.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. TPS498-TPS498
Author(s):  
Petros Grivas ◽  
Scott T. Tagawa ◽  
Joaquim Bellmunt ◽  
Maria De Santis ◽  
Ignacio Duran ◽  
...  
Keyword(s):  
Clinical Benefit ◽  
Topoisomerase I ◽  
Progressive Disease ◽  
Group Performance ◽  
Checkpoint Inhibitor ◽  
Single Agent ◽  
Objective Response ◽  
Locally Advanced ◽  
Eastern Cooperative Oncology Group ◽  
Phase Iii

TPS498 Background: Treatment options are limited for patients with locally advanced unresectable or metastatic urothelial carcinoma (mUC) who progress following prior platinum-based and checkpoint inhibitor (CPI) therapy. Sacituzumab govitecan (SG) is an antibody-drug conjugate consisting of an anti–Trop-2 monoclonal antibody coupled to SN-38 (an active metabolite of irinotecan, a topoisomerase-I inhibitor) via a unique hydrolyzable linker. A phase II registrational study, TROPHY-U-01 study, confirmed the initial positive efficacy signal in mUC. SG demonstrated an objective response rate (ORR) of 27% and median overall survival (OS) of 10.5 months in patients with mUC (median 3 prior lines of therapy and 87% with ≥1 Bellmunt risk factors) who progressed after prior platinum-based and CPI therapies (n=113; Loriot ESMO 2020). The results compared favorably with historic single-agent chemotherapy (ORR ~10%; OS ≤7 months). A phase III trial has been initiated to confirm these findings. Methods: TROPiCS-04 (NCT04527991) is a global, multicenter, open-label, randomized, controlled trial in patients with locally advanced unresectable or mUC who progressed after prior platinum-based and CPI therapies (with Eastern Cooperative Oncology Group performance status 0–1 and adequate hematologic, hepatic, and renal function). Patients will be randomized 1:1 to receive SG 10 mg/kg intravenously (IV) on day 1 and 8 of 21-day cycles or single-agent treatment of physician’s choice (paclitaxel 175 mg/m2, docetaxel 75 mg/m2, or vinflunine 320 mg/m2 IV on day 1 of 21-day cycles) until progressive disease, unacceptable toxicity, or withdrawal of consent. Treatment beyond progressive disease may be permitted in patients deemed to be receiving clinical benefit per investigator assessment. Approximately 482 patients will be enrolled to provide 90% power on the primary endpoint of OS. Secondary endpoints include progression-free survival, ORR, clinical benefit rate, duration of response (all per Response Evaluation Criteria in Solid Tumors v1.1), safety, and quality of life. Study initiation is ongoing and enrollment begins in Q4 2020 across ~90 sites. Clinical trial information: NCT04527991.

Response to selpercatinib versus prior systemic therapy in patients (pts) with RET fusion+ non-small-cell lung cancer (NSCLC).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 9032-9032
Author(s):  
Alexander E. Drilon ◽  
Oliver Gautschi ◽  
Benjamin Besse ◽  
Vivek Subbiah ◽  
Daniel Shao-Weng Tan ◽  
...  
Keyword(s):  
Systemic Therapy ◽  
Kinase Inhibitor ◽  
Phase 1 ◽  
Single Agent ◽  
Objective Response ◽  
Progression Free Survival ◽  
Survival Duration ◽  
Prior Therapy ◽  
Platinum Based Chemotherapy ◽  
Systemic Therapies

9032 Background: Selpercatinib, a first-in-class highly selective, potent, CNS-active RET kinase inhibitor, is approved in multiple countries for treatment of RET fusion+ lung or thyroid cancers. Selpercatinib demonstrated durable antitumor activity in previously treated pts with RET fusion+ NSCLC in an ongoing Phase 1/2 trial, LIBRETTO-001 (Besse et al., ASCO 2021). Methods: Pts with RET fusion+ NSCLC enrolled in the global, multicenter, LIBRETTO-001 trial (NCT03157128; 16 countries, 89 sites). Primary endpoint was objective response rate (ORR). Secondary endpoints included progression-free survival, duration of response, and safety. This post-hoc intrapatient analysis was based on a 30 March 2020 data cutoff date. Historical physician-reported best overall response (BOR) from last systemic therapy received prior to enrollment was compared with selpercatinib BOR by independent review committee per RECIST v1.1, with each patient serving as his/her own control. Results: In efficacy-evaluable pts (N = 218) who previously received platinum-based chemotherapy (chemo), median pt age was 61 years, the majority with ECOG of 0/1 (37%/61%), with a median of 2 (range: 1-15) prior systemic therapies. Overall, 57% of patients responded to selpercatinib while 16% responded to the immediate prior therapy. ORR improvements with selpercatinib were observed regardless of prior therapy: chemotherapy + immune checkpoint inhibitor (ICI) (57% vs 14%), single-agent ICI (48% vs 3%), or chemotherapy (58% vs 15%). A total of 108 patients (49%) did not respond to immediate prior therapy but responded to selpercatinib. Fewer patients had progressive disease as their BOR with selpercatinib (2%) compared to the immediate prior therapy (28%). The median duration of therapy for selpercatinib was notably extended compared with that of the immediate prior therapy (11.8 vs. 3.4 months, respectively). Conclusions: In pts with RET fusion+ NSCLC treated on LIBRETTO-001, systemic therapies administered prior to enrollment achieved less meaningful clinical benefit than selpercatinib. Selpercatinib demonstrated consistent efficacy regardless of the type of prior therapy. Clinical trial information: NCT03157128.

scholarly journals Atezolizumab in locally advanced or metastatic urothelial cancer: a pooled analysis from the Spanish patients of the IMvigor 210 cohort 2 and 211 studies

2020 ◽  
Author(s):  
M. Sotelo ◽  
T. Alonso-Gordoa ◽  
P. Gajate ◽  
E. Gallardo ◽  
R. Morales-Barrera ◽  
...  
Keyword(s):  
Median Duration ◽  
Urothelial Cancer ◽  
Objective Response ◽  
Locally Advanced ◽  
Survival Rates ◽  
Pooled Analysis ◽  
Metastatic Urothelial Cancer ◽  
Platinum Based Chemotherapy ◽  
Geographical Regions ◽  
Duration Of Response

Abstract Background The studies IMvigor 210 cohort 2 and IMvigor211 evaluated the efficacy of atezolizumab in patients with locally advanced or metastatic urothelial cancer (mUC) upon progression to platinum-based chemotherapy worldwide. Yet, the real impact of this drug in specific geographical regions is unknown. Materials and methods We combined individual-level data from the 131 patients recruited in Spain from IMvigor210 cohort 2 and IMvigor211 in a pooled analysis. Efficacy and safety outcomes were assessed in the overall study population and according to PD-L1 expression on tumour-infiltrating immune cells. Results Full data were available for 127 patients; 74 (58%) received atezolizumab and 53 (42%) chemotherapy. Atezolizumab patients had a numerically superior median overall survival although not reaching statistical significance (9.2 months vs 7.7 months). No statistically significant differences between arms were observed in overall response rates (20.3% vs 37.0%) or progression-free survival (2.1 months vs 5.3 months). Nonetheless, median duration of response was superior for the immunotherapy arm (non-reached vs 6.4 months; p = 0.005). Additionally, among the responders, the 12-month survival rates seemed to favour atezolizumab (66.7% vs 19.9%). When efficacy was analyzed based on PD-L1 expression status, no significant differences were found. Treatment-related adverse events of any grade occurred more frequently in the chemotherapy arm [46/57 (81%) vs 44/74 (59%)]. Conclusion Patients who achieved an objective response on atezolizumab presented a longer median duration of response and numerically superior 12 month survival rates when compared with chemotherapy responders along with a more favorable safety profile. PD-L1 expression did not discriminate patients who might benefit from atezolizumab.

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