Safety and efficacy of rogaratinib in combination with atezolizumab in cisplatin-ineligible patients (pts) with locally advanced or metastatic urothelial cancer (UC) and FGFR mRNA overexpression in the phase Ib/II FORT-2 study.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 4521-4521
Author(s):  
Jonathan E. Rosenberg ◽  
Pablo Gajate ◽  
Rafael Morales-Barrera ◽  
Jae-Lyun Lee ◽  
Andrea Necchi ◽  
...  
Keyword(s):  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Performance Status ◽  
Objective Response ◽  
Locally Advanced ◽  
First Line ◽  
Archival Tissue ◽  
Phase Ib ◽  
Metastatic Urothelial Cancer ◽  
L1 Protein

4521 Background: Rogaratinib (R) is a novel pan-FGFR inhibitor that showed promising efficacy and safety in a Phase I trial in pts with advanced solid tumors, including UC, with FGFR1-3 mRNA overexpression. The Phase Ib/II FORT-2 study (NCT03473756) of R plus atezolizumab (A) in pts with first-line cisplatin-ineligible, FGFR-positive, advanced/metastatic UC previously identified a maximum tolerated dose of R 600 mg twice daily (BID) plus A (1200 mg every 3 weeks) . We report updated safety, efficacy, and the recommended Phase II dose (RP2D) for combination therapy from the Phase Ib study. Methods: Pts with cisplatin-ineligible, locally advanced/metastatic UC with FGFR1/3 mRNA overexpression detected by RNA in situ hybridization of archival tissue (RNAscope) received oral R 600 mg BID plus A 1200 mg on day 1 of a 21-day cycle. Archival tissue was examined for programmed cell-death ligand 1 (PD-L1) protein expression levels, FGFR3-activating mutations via a targeted Illumina NGS panel, and FGFR fusions via an Archer fusion plex assay. Primary objectives were safety, tolerability, and determination of the RP2D. Results: 26 pts (enrolled May 25, 2018 to Nov 25, 2020) were treated; 89% were male, median age was 76 years (range 47-85), 58% had an ECOG performance status of 1, and 77% displayed low or absent (negative or non-detectable) PD-L1 expression (combined positive score < 10%). Common treatment-emergent adverse events (TEAEs) included diarrhea (n = 17, 65%; 1 grade [G] 3), hyperphosphatemia (n = 15, 58%; all G1 or 2), and nausea (n = 11, 42%; 1 G3). The most common G3/4 TEAEs were elevated lipase without pancreatitis (n = 5, 19%), elevated amylase (n = 3, 12%), and rash and syncope (n = 2, 8% each). TEAEs led to interruption/reduction/discontinuation of R in 69%/46%/19% of pts. R-related unique TEAEs were hyperphosphatemia in 15 pts (58%) and retinal pigment epithelium detachment in 1 pt (4%). G5 events occurred in 3 pts (12%), unrelated to treatment. 13 of 24 evaluable pts (54%) had an objective response (OR) per RECIST v1.1. The disease control rate was 83%, including 3 pts (13%) with a complete response (CR), 10 (42%) with a partial response (PR), and 7 (29%) with stable disease. Median duration of response was not reached. OR rate was 56% (2 CRs and 7 PRs) in the 16 pts with tumors having low/negative PD-L1 protein and FGFR3 mRNA overexpression without mutation. The RP2D for R+A was 600 mg BID. Conclusions: First-line treatment with the RP2D of R+A achieved favorable clinical efficacy and tolerability in pts with cisplatin-ineligible, metastatic UC characterized by high FGFR1/3 mRNA expression and generally low/negative PD-L1 expression. Encouraging efficacy was observed regardless of PD-L1 expression or FGFR3 mutation status, warranting future investigation. Clinical trial information: NCT03473756.

Safety and preliminary efficacy of rogaratinib in combination with atezolizumab in a phase Ib/II study (FORT-2) of first-line treatment in cisplatin-ineligible patients (pts) with locally advanced or metastatic urothelial cancer (UC) and FGFR mRNA overexpression.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 5014-5014 ◽  
Author(s):  
Jonathan E. Rosenberg ◽  
Pablo Gajate ◽  
Rafael Morales-Barrera ◽  
Jae-Lyun Lee ◽  
Andrea Necchi ◽  
...  
Keyword(s):  
Immune Escape ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Objective Response ◽  
Locally Advanced ◽  
Complete Response ◽  
Maximum Tolerated Dose ◽  
Phase Ib ◽  
Metastatic Urothelial Cancer ◽  
Ecog Ps

5014 Background: Programmed cell-death ligand 1 (PD-L1) overexpression is a mechanism for immune escape in UC. Rogaratinib, an oral pan-FGFR1-4 inhibitor, showed promising efficacy in a Phase I study in pts with solid tumors, including UC, with FGFR1-3 mRNA overexpression (Schuler et al. Lancet Oncol 2019). This Phase Ib/II study is evaluating rogaratinib in combination with atezolizumab, a PD-L1 inhibitor, in pts with FGFR-positive, locally advanced or metastatic UC (NCT03473756). We report results from the Phase Ib study. Methods: Cisplatin-ineligible pts with untreated metastatic UC were eligible if high FGFR1 or 3 mRNA was detected by RNA in situ hybridization of archival tissue (RNAscope). Pts were treated at a starting dose of rogaratinib 800 mg p.o. BID and atezolizumab 1200 mg i.v. on day 1 (21-day cycle). Primary objectives were safety, tolerability, and determination of the recommended Phase II dose. Results: 27 pts were treated (rogaratinib 800 mg + atezolizumab, n = 11; rogaratinib 600 mg + atezolizumab, n = 16); 85% were male, median age was 72 years (range 47-83), 37% had an ECOG PS of 1, and 96% had negative/low PD-L1 expression. Most common treatment-emergent adverse events (TEAEs) were diarrhea (63%), hyperphosphatemia (44%), and urinary tract infection (37%). Dose interruption/reduction due to AEs occurred in 67%/37% of pts; TEAEs lead to discontinuation in 45.5% (800 mg) and 12.5% (600 mg). Most common grade 3/4 TEAEs were increased lipase without pancreatitis (11%), rash, and increased alanine aminotransferase (7% each). Rogaratinib-related unique TEAEs were hyperphosphatemia (44%) and retinal pigment epithelium detachment (4%). The maximum tolerated dose (MTD) was rogaratinib 600 mg BID based on lower overall frequency of AEs. Of 23 evaluable pts (600 mg, n = 13; 800 mg, n = 10), overall 9 (39%) pts had an objective response (RECIST v1.1); 3 (13%) pts had a complete response (600 mg: 2/13 pts), 6 (26%) pts had a partial response (600 mg: 5/13 pts), and 6 (26%) pts had stable disease (600 mg: 4/13 pts). Conclusions: Rogaratinib with atezolizumab showed promising efficacy and safety in cisplatin-ineligible pts with tumor FGFR1 or 3 mRNA-positive UC, with nearly all pts demonstrating low or negative PD-L1 expression. Pts are being enrolled at the MTD of rogaratinib 600 mg BID plus atezolizumab. Clinical trial information: NCT03473756 .

A phase Ib single-arm study of bintrafusp alfa for the treatment of pretreated, locally advanced/unresectable or metastatic urothelial cancer.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. TPS501-TPS501
Author(s):  
Petros Grivas ◽  
Rafael Morales-Barrera ◽  
Srikala S. Sridhar ◽  
Yohann Loriot ◽  
Michiel Simon Van Der Heijden ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Safety Profile ◽  
Urothelial Cancer ◽  
Objective Response ◽  
Locally Advanced ◽  
Unmet Need ◽  
Type I ◽  
First Line ◽  
Phase Ib ◽  
Metastatic Urothelial Cancer

TPS501 Background: Urothelial cancer (UC) is the most common histological subtype of bladder cancer. For patients with metastatic UC, platinum-containing chemotherapy (CT) is the first-line standard of care. With 5 PD-(L)1 inhibitors approved for second-line treatment of platinum-refractory advanced UC, objective response rates (ORRs) in this setting (15% to 21%) and in first-line cisplatin-ineligible patients (23% to 31%) suggest that there remains a significant unmet need for improved outcomes. TGF-β signaling has been associated with resistance to PD-(L)1 inhibitors in patients with UC. Bintrafusp alfa (BA) is a first-in-class bifunctional fusion protein composed of the extracellular domain of the TGF-βRII receptor (a TGF-β “trap”) fused to a human IgG1 mAb blocking PD-L1. In murine models, BA resulted in improved antitumor activity vs TGF-β or PD-L1 monotherapies alone or in combination. In 2 phase I trials (NCT02517398 and NCT02699515), BA demonstrated a manageable safety profile and encouraging clinical efficacy in >670 patients with advanced solid tumors. Here we describe a phase Ib study (NCT04349280) that will assess the clinical activity and safety profile of BA in platinum-experienced patients with locally advanced/unresectable or metastatic UC. Colocalized, simultaneous inhibition of the TGF-β and PD-L1 pathways by BA is hypothesized to elicit greater antitumor activity than anti–PD-(L)1 therapies in patients with UC. Methods: This open-label, multicenter, single-arm trial is accruing patients with histologically confirmed locally advanced/unresectable or metastatic UC (ECOG PS ≤1) with disease progression or recurrence after platinum-based CT. Patients must not have received >2 lines of systemic therapy for metastatic disease or prior therapy targeting T-cell costimulation, or checkpoint or TGF-β pathways. Patients with pneumonitis or a history of noninfectious pneumonitis that required systemic immunosuppression are ineligible. Patients will receive BA 1200 mg every 2 weeks until progression, unacceptable toxicity, death, or study withdrawal, or for up to 2 years. The primary endpoint is investigator-assessed confirmed ORR per RECIST 1.1; key secondary endpoints include duration of response and progression-free survival per the investigator and IRC, overall survival, safety, immunogenicity, and pharmacokinetics. Exploratory biomarker analyses will be conducted using patient samples collected during screening and prior to administration of BA. The base ORR used for the null hypothesis is 21%, and the target ORR is 40%. Using a predictive probability design and an estimated enrollment of 40 patients, the type I error rate is 5.70% and the power is 85.39%. As of September 2020, 3 sites in 2 countries have been activated and no patients have been enrolled. Clinical trial information: NCT04349280.

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).

Cougar-02: A randomized phase III study of docetaxel versus active symptom control in patients with relapsed esophago-gastric adenocarcinoma.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 4023-4023 ◽  
Author(s):  
Natalie Cook ◽  
Andrea Marshall ◽  
Jane M. Blazeby ◽  
John A. Bridgewater ◽  
Jonathan Wadsley ◽  
...  
Keyword(s):  
Gastric Adenocarcinoma ◽  
Performance Status ◽  
Symptom Control ◽  
Objective Response ◽  
Locally Advanced ◽  
Median Number ◽  
Phase Iii ◽  
First Line ◽  
Open Label ◽  
Line Chemotherapy

4023 Background: Survival in patients who relapse after first-line chemotherapy (CT) for advanced esophago-gastric adenocarcinoma (EGC) is poor though recently randomised trials (RCT) have suggested a small benefit for second line chemotherapy with taxanes or irinotecan. There is very little data on health related quality of life (HRQL) or overall survival (OS), particularly in patients who progress shortly after first-line therapy. Methods: COUGAR-02 was a multicentre open-label, phase III RCT for patients with locally advanced or metastatic EGC of performance status (PS) 0-2 who had progressed within 6 months of previous platinum/fluoropyrimidine CT. Patients were randomised (1:1) to receive either docetaxel 75mg/m2every 3 weeks for up to 6 cycles or active symptom control (ASC). The primary endpoint was OS. The secondary endpoint of HRQL, assessed using EORTC QLQ-C30 and QLQ-ST022, was analysed using standardised area under a curve and compared using Wilcoxon rank sum test. Sensitivity analysis adjusting for dropouts due to death were performed using quality adjusted survival. Results: 168 patients (84 patients in each arm) were recruited between April 2008 and April 2012. Median age was 65 years (range 28-84); 81% were males. PS at randomisation was 0 for 27%, 1 for 57% and 2 for 15%. 86% had metastatic disease. 43% progressed during previous CT, 28% progressed within 3 months of end of previous CT and 29% progressed between 3 and 6 months. Median number of cycles of docetaxel was 3. 23% completed 6 cycles. Docetaxel was well tolerated and resulted in a significantly improved OS over ASC alone (HR=0.67 (95% CI 0.49-0.92); p=0.01). Objective response rate was 7%. For QLQ-C30, patients on docetaxel arm reported significantly less pain (p=0.0008) and trend for less nausea and vomiting (p=0.02) and constipation (p=0.02) than those on ASC arm. Similar global HRQL seen (p=0.53).For QLQ-ST022, trend seen for less dysphagia (p=0.02) and pain symptoms (p=0.01) for patients on docetaxel arm than ASC Conclusions: Docetaxel provided a significant OS benefit over ASC with improvements in symptom scores and no loss in overall HRQL. Docetaxel can be considered a standard of care in this setting. Clinical trial information: NCT00978549.

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.

BOLERO-1: A randomized, phase III, double-blind, placebo-controlled multicenter trial of everolimus in combination with trastuzumab and paclitaxel as first-line therapy in women with HER2-positive (HER2+), locally advanced or metastatic breast cancer (BC).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. TPS648-TPS648 ◽  
Author(s):  
Sara A. Hurvitz ◽  
Fabrice Andre ◽  
Howard A. Burris ◽  
Masakazu Toi ◽  
Marc E. Buyse ◽  
...  
Keyword(s):  
Standard Therapy ◽  
Performance Status ◽  
Objective Response ◽  
Locally Advanced ◽  
Metastatic Breast ◽  
Phase Iii ◽  
Trastuzumab Resistance ◽  
First Line ◽  
Double Blind ◽  
Good Tolerability

TPS648 Background: Up to 25% of BCs overexpress human epidermal growth factor receptor 2 (HER2). Patients with HER2+ disease have a higher rate of relapse and shorter overall survival (OS). Trastuzumab, a monoclonal antibody targeting HER2, is the standard of care and improves OS for HER2+ BC, but acquired resistance is common. The combination of trastuzumab and paclitaxel has shown good tolerability and excellent objective response rates (ORR) in up to 84% of patients with HER2+ metastatic BC (MBC) (Gasparini G, et al. BCRT. 2007;101:355-65). Everolimus is an orally bioavailable inhibitor of mammalian target of rapamycin (mTOR), a protein kinase central to multiple protein synthesis pathways and implicated in trastuzumab resistance. Everolimus-containing regimens have shown promising results in patients with ER+, HER2– advanced BC in phase II/III trials; everolimus plus trastuzumab/paclitaxel or vinorelbine has shown encouraging ORR with an acceptable safety profile in phase I/II trials in patients with HER2+ MBC. The present phase III study was undertaken to assess the effectiveness of adding everolimus to first-line standard therapy in HER2+ advanced BC. Methods: Women with HER2+, locally advanced or metastatic BC who have received no prior systemic therapy (except endocrine) are eligible. Local disease must not be amenable to resection with curative intent. Women with a history of central nervous system metastasis are excluded. Patients are randomized 2:1 (everolimus vs control) to receive standard therapy (paclitaxel and trastuzumab) plus everolimus (10 mg daily) or placebo. The primary endpoint is progression-free survival. Secondary endpoints include OS, ORR, and clinical benefit rate. Additional endpoints are safety, performance status, and biomarkers. This trial is sponsored by Novartis Pharmaceuticals and is registered (ClinicalTrials.gov: NCT00876395). Enrollment began September 2009, with a planned accrual of 717. The current accrual is 719, and the estimated primary completion date is October 2012.

Long-Term Outcomes in KEYNOTE-052: Phase II Study Investigating First-Line Pembrolizumab in Cisplatin-Ineligible Patients With Locally Advanced or Metastatic Urothelial Cancer

2020 ◽  
Vol 38 (23) ◽  
pp. 2658-2666 ◽  
Author(s):  
Jacqueline Vuky ◽  
Arjun V. Balar ◽  
Daniel Castellano ◽  
Peter H. O’Donnell ◽  
Petros Grivas ◽  
...  
Keyword(s):  
Lymph Node ◽  
Partial Response ◽  
Phase Ii ◽  
Objective Response ◽  
Locally Advanced ◽  
First Line ◽  
Metastatic Urothelial Cancer ◽  
Duration Of Response ◽  
Positive Score ◽  
Combined Positive Score

PURPOSE The phase II single-arm KEYNOTE-052 study evaluated the efficacy and safety of first-line pembrolizumab for patients with locally advanced or metastatic cisplatin-ineligible urothelial carcinoma (UC). PATIENTS AND METHODS Three hundred seventy patients received pembrolizumab 200 mg intravenously every 3 weeks for up to 24 months. Positive tumor programmed death ligand 1 (PD-L1) expression was defined as combined positive score (CPS) ≥ 10. Response was assessed by independent central review every 9 weeks per RECIST v1.1. The primary end point was objective response rate (ORR). RESULTS At data cutoff (September 26, 2018), the minimum follow-up was 2 years since the last patient enrolled. ORR was 28.6% (95% CI, 24.1% to 33.5%); 33 patients (8.9%) and 73 patients (19.7%) achieved complete and partial response, respectively. The median duration of response was 30.1 months (95% CI, 18.1 months to not reached [NR]); responses lasted ≥ 12 and ≥ 24 months in 67% and 52% of patients, respectively. Forty patients with complete or partial response completed 2 years of study treatment, and 32 had ongoing response at completion. Median overall survival (OS) was 11.3 months (95% CI, 9.7 to 13.1 months), and 12- and 24-month OS rates were 46.9% and 31.2%, respectively. In patients with CPS ≥ 10, ORR was 47.3% (95% CI, 37.7% to 57.0%) and median OS was 18.5 months (95% CI, 12.2 to 28.5 months). In patients with lymph node–only disease, ORR was 49.0% (95% CI, 34.8% to 63.4%), and median OS was 27.0 months (12.4 months to NR). There were no new safety signals. CONCLUSION First-line pembrolizumab confers meaningful and durable clinical response in cisplatin-ineligible patients with advanced UC and is associated with prolonged OS, particularly with PD-L1 CPS ≥ 10 and lymph node–only disease.

scholarly journals Complete Response With Immunotherapy: A Case of Metastatic Bladder Cancer

2021 ◽  
Vol 9 ◽  
pp. 232470962110356
Author(s):  
Balraj Singh ◽  
Parminder Kaur ◽  
Sachin Gupta ◽  
Nirmal Guragai ◽  
Michael Maroules
Keyword(s):  
Bladder Cancer ◽  
Cancer Immunotherapy ◽  
Locally Advanced ◽  
Complete Response ◽  
First Line ◽  
Novel Therapy ◽  
Metastatic Bladder Cancer ◽  
Metastatic Urothelial Cancer ◽  
Platinum Based Chemotherapy ◽  
Broad Variety

Bladder cancer is the most common urinary tract malignancy. Platinum-based chemotherapy is the first line of treatment in locally advanced or metastatic bladder cancer. Immunotherapy has become a novel therapy option in a broad variety of malignancies including bladder cancer. Immunotherapy is approved as first line of treatment in patients who are ineligible for platinum-based chemotherapy and second-line treatment for metastatic urothelial cancer who progressed after platinum-based treatments. We present the case of an 83-year-old female with metastatic bladder cancer who was chemotherapy ineligible and had complete response with immune checkpoint inhibitor pembrolizumab.

First-line nivolumab (NIVO) plus ipilimumab (IPI) plus two cycles of chemotherapy (chemo) versus chemo alone (4 cycles) in patients with advanced non-small cell lung cancer (NSCLC): Two-year update from CheckMate 9LA.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 9000-9000
Author(s):  
Martin Reck ◽  
Tudor-Eliade Ciuleanu ◽  
Manuel Cobo ◽  
Michael Schenker ◽  
Bogdan Zurawski ◽  
...  
Keyword(s):  
Clinical Benefit ◽  
Performance Status ◽  
Objective Response ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Expression Level ◽  
First Line ◽  
Ecog Performance Status ◽  
Grade 3

9000 Background: In the randomized phase 3 CheckMate 9LA trial (NCT03215706), first-line NIVO + IPI combined with 2 cycles of chemo significantly improved overall survival (OS), progression-free survival (PFS), and objective response rate (ORR) vs chemo alone (4 cycles). Clinical benefit was observed regardless of programmed death ligand 1 (PD-L1) expression level and histology. Here we report data with 2 years’ minimum follow-up from this study. Methods: Adult patients (pts) with stage IV / recurrent NSCLC, ECOG performance status ≤ 1, and no known sensitizing EGFR/ALK alterations were stratified by PD-L1 (< 1% vs ≥ 1%), sex, and histology (squamous vs non-squamous) and were randomized 1:1 to NIVO 360 mg Q3W + IPI 1 mg/kg Q6W + chemo (2 cycles; n = 361) or chemo alone (4 cycles; n = 358). Pts with non-squamous NSCLC in the chemo-alone arm could receive pemetrexed maintenance. The primary endpoint was OS. Secondary endpoints included PFS and ORR by blinded independent central review, and efficacy by different PD-L1 levels. Safety was exploratory. Results: At a minimum follow-up of 24.4 months for OS (database lock: Feb 18, 2021), pts treated with NIVO + IPI + chemo continued to derive OS benefit vs chemo, with a median OS of 15.8 months vs 11.0 months, respectively (HR, 0.72 [95% CI, 0.61–0.86]); 2-year OS rates were 38% vs 26%. Median PFS with NIVO + IPI + chemo vs chemo was 6.7 months vs 5.3 months (HR, 0.67 [95% CI, 0.56–0.79]); 8% and 37% of pts who had disease progression received subsequent immunotherapy, respectively. ORR was 38% with NIVO + IPI + chemo vs 25% with chemo. Similar clinical benefit with NIVO + IPI + chemo vs chemo was observed in all randomized pts and across the majority of subgroups, including by PD-L1 expression level (Table) or histology. Any grade and grade 3–4 treatment-related adverse events were reported in 92% and 48% of pts in the NIVO + IPI + chemo arm vs 88% and 38% in the chemo arm, respectively. Conclusion: With 2 years’ minimum follow-up, first-line NIVO + IPI + chemo demonstrated durable survival and benefit versus chemo in pts with advanced NSCLC; no new safety signals were identified. Clinical trial information: NCT03215706. [Table: see text]

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