FP201INTERIM RESULTS FROM AN ONGOING PHASE 2 STUDY EVALUATING THE USE OF A MASP-2 INHIBITOR FOR THE TREATMENT OF IGA NEPHROPATHY (IGAN)

2019 ◽  
Vol 34 (Supplement_1) ◽  
Author(s):  
Jonathan Barratt ◽  
Eckhard Leifke ◽  
Steve Whitaker ◽  
Louis DeTulleo ◽  
Richard Lafayette
Keyword(s):  
Iga Nephropathy ◽  
Phase 2 ◽  
Phase 2 Study ◽  
Ongoing Phase

scholarly journals AN ONGOING PHASE 2 STUDY OF IBRUTINIB COMBINED WITH VENETOCLAX IN PATIENTS WITH TREATMENT-NAÏVE CLL/SLL

2017 ◽  
Vol 35 ◽  
pp. 428-428 ◽  
Author(s):  
P. Ghia ◽  
C.S. Tam ◽  
T. Siddiqi ◽  
D. Stevens ◽  
I.W. Flinn ◽  
...  
Keyword(s):  
Phase 2 ◽  
Phase 2 Study ◽  
Treatment Naïve ◽  
Ongoing Phase

scholarly journals Randomized, Open-Label, Multicenter, Phase 2 Study of Asciminib (ABL001) As an Add-on to Imatinib Versus Continued Imatinib Versus Switch to Nilotinib in Patients with Chronic Myeloid Leukemia in Chronic Phase Who Have Not Achieved a Deep Molecular Response with Frontline Imatinib

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5910-5910
Author(s):  
Giuseppe Saglio ◽  
Timothy P. Hughes ◽  
Jan Geissler ◽  
Shruti Kapoor ◽  
Anne-Sophie Longin ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Research Funding ◽  
Chronic Phase ◽  
Molecular Response ◽  
Phase 2 ◽  
Atp Binding Site ◽  
Phase 2 Study ◽  
Deep Molecular Response ◽  
Ongoing Phase

Background: In patients with chronic myeloid leukemia in chronic phase (CML-CP), the efficacy of ATP-competitive tyrosine kinase inhibitors (TKIs) has resulted in treatment-free remission (TFR) as a primary treatment goal for those with a sustained deep molecular response (DMR). However, most patients treated with imatinib fail to achieve a sustained DMR, meaning that they cannot benefit from TFR. Asciminib is a potent and specific inhibitor of BCR-ABL1. Unlike BCR-ABL1 TKIs that target the ATP binding site, asciminib binds to the myristate pocket of ABL1. Preclinical data showed that the combination of asciminib with ATP-competitive TKIs may provide more potent BCR-ABL1 inhibition and prevent emergence of resistance mutations (Wylie et al. Nature. 2017;543:733-737). In an ongoing phase 1 study (NCT02081378), asciminib demonstrated clinical activity and was well tolerated as a single agent (Hughes et al. Blood. 2016;128 [abstract 625]). In the same study, asciminib in combination with imatinib showed promising preliminary efficacy and a good safety profile in patients resistant/intolerant of ≥2 prior TKIs (Cortes et al. HemaSphere. 2019;3(S1) [abstract S388]). These findings informed the dose of asciminib to be further evaluated in combination with imatinib. An ongoing phase 3 study (NCT03106779) is evaluating asciminib vs bosutinib in patients previously treated with ≥2 ATP-binding site TKIs (Mauro et al. J Clin Oncol. 2019;37 [abstract TPS7070]). Here, we describe the ASCiminib add-on 4-arm study evaluating MOlecular REsponse (ASC4MORE) in patients. This is a phase 2 study evaluating the efficacy of adding asciminib to ongoing imatinib therapy in patients with CML-CP who have not achieved DMR with long-term frontline imatinib (CABL001E2201; NCT03578367). Methods: Study participants are aged ≥18 years, have CML-CP, and have been treated with frontline imatinib for ≥12 months. Study entry requires patients to be receiving imatinib 400 mg once daily (QD) at randomization, have BCR-ABL1 transcript levels in the range of ≤1% to >0.01% on the International Scale (IS), no prior achievement of MR4 (BCR-ABL1IS ≤0.01%) confirmed by two consecutive tests, and no prior treatment failure. Overall, ~80 patients will be randomized 1:1:1:1 to one of four arms (Figure): either asciminib 40 mg QD or 60 mg QD added to imatinib 400 mg QD; continued treatment with imatinib 400 mg QD; or switch to nilotinib 300 mg twice daily. Study treatment will continue until treatment resistance or intolerance, or up to 96 weeks after the last randomized patient has begun treatment. The primary objective of this study is to assess whether asciminib add-on to imatinib is more effective than imatinib continuation; the primary endpoint is the rate of MR4.5 (BCR-ABL1IS ≤0.0032%) at 48 weeks. Secondary objectives include: to estimate the efficacy of switch to nilotinib; to estimate the difference in efficacy between asciminib add-on to imatinib and switch to nilotinib; and to characterize the safety of asciminib add-on to imatinib. Exploratory objectives include TFR eligibility at the end of the study and patient-reported outcomes. Patients in the imatinib continuation arm who have not achieved MR4.5 at 48 weeks may cross over to receive add-on asciminib. This study is ongoing, with 23 patients randomized as of 22 July 2019. Disclosures Saglio: BMS: Consultancy; Novartis: Consultancy; Ariad: Consultancy; Incyte: Consultancy; Pfizer: Consultancy; Jansen: Consultancy; Celgene: Consultancy. Hughes:Novartis, Bristol-Myers Squibb, Celgene: Research Funding; Novartis, Bristol-Myers Squibb: Consultancy, Other: Travel. Geissler:Novartis: Consultancy, Research Funding, Speakers Bureau; Pfizer: Consultancy, Research Funding, Speakers Bureau; Roche: Consultancy; Amgen: Consultancy; Incyte: Research Funding; Takeda: Research Funding; Biomarin: Consultancy; Bristol-Myers Squibb: Consultancy, Research Funding, Speakers Bureau; Janssen: Consultancy, Speakers Bureau; UCB: Consultancy, Speakers Bureau; Servier: Consultancy. Kapoor:Novartis: Employment. Longin:Novartis: Employment. Mukherjee:Novartis: Employment. Cortes:Novartis: Consultancy, Honoraria, Research Funding; Daiichi Sankyo: Consultancy, Honoraria, Research Funding; BiolineRx: Consultancy; Jazz Pharmaceuticals: Consultancy, Research Funding; Merus: Consultancy, Honoraria, Research Funding; Forma Therapeutics: Consultancy, Honoraria, Research Funding; Immunogen: Consultancy, Honoraria, Research Funding; Astellas Pharma: Consultancy, Honoraria, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Takeda: Consultancy, Research Funding; Biopath Holdings: Consultancy, Honoraria; Sun Pharma: Research Funding; Pfizer: Consultancy, Honoraria, Research Funding.

256 Single-agent zalifrelimab (anti-CTLA-4) shows clinical benefit in rare tumors – case report from phase 2 study (NCT03104699)

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A279-A279
Author(s):  
Cesar Perez ◽  
Robert Wesolowski ◽  
Breelyn Wilky ◽  
Waldo Ortuzar Feliu ◽  
Hong Zhang ◽  
...  
Keyword(s):  
Solid Tumors ◽  
Clinical Benefit ◽  
Spindle Cell ◽  
Spindle Cell Sarcoma ◽  
Phase 2 ◽  
Cell Sarcoma ◽  
Phase 2 Study ◽  
Disease Stabilization ◽  
Tumor Types ◽  
Ongoing Phase

BackgroundZalifrelimab is a fully human monoclonal antibody against cytotoxic T-lymphocyte -associated protein 4 (CTLA-4). Preliminary data demonstrated clinical benefit and tolerability, as monotherapy, in patients with recurrent solid tumors including rare tumor types. Previously presented Phase I data reported one durable complete response in recurrent cutaneous angiosarcoma (cAS).1 Here we report additional clinical responses from an ongoing Phase 2 study of zalifrelimab monotherapy including clinical benefit in rare solid tumors.MethodsIn an ongoing, phase 2 study (NCT03104699), the safety and efficacy of zalifrelimab, as monotherapy, was evaluated in patients who progressed on prior anti-PD-1/L1 treatment. All patients were treated intravenously (IV) with zalifrelimab at 1 mg/kg every 3 weeks until disease progression or up to 2 years.ResultsOverall, 44 patients were treated and 29 patients were response-evaluable at the time of report. In patients with refractory solid tumors treated with zalifrelimab, we report a disease control rate (CR, PR, and SD) of 51.7%, objective response rate (ORR) of 10.3% (3/29), disease stabilization of 41.3% (12/29). Clinical activity was observed in five solid tumors considered rare, including; cAS (N=1), glucagonoma (N=1), chondrosarcoma (N=1), spindle-cell sarcoma (N=1) and fibroblastic sarcoma (N=1). In these rare tumors, durable partial responses of 45 and 30 weeks were observed in cAS of the scalp with lymph node metastases and glucagonoma, respectively. Both patients remain on zalifrelimab with no evidence of disease progression. Additionally, durable disease stabilization was observed in a patient with spindle-cell sarcoma. Patients with chondrosarcoma and fibroblastic sarcoma progressed on therapy. Zalifrelimab was well tolerated with the most commonly reported treatment-related adverse events including fatigue, nausea, anemia, diarrhea and vomiting, consistent with the drug class. Most events were mild or moderate and resolved with standard treatments.ConclusionsOur data demonstrates the potential for Zalifrelimab to promote meaningful clinical benefit in difficult to treat tumors, including patients that progress on prior PD-1/PD-L1 therapy or chemotherapy. Notably, responses were observed in rare tumor types such as recurrent cutaneous angiosarcoma and glucagonoma. Treatment with zalifrelimab is safe and well tolerated in patients with advanced malignancies.Trial RegistrationNCT03104699.ReferenceVaia Florou, Andrew E Rosenberg, Eric Wieder, Krishna V. Komanduri, Despina Kolonias, Mohamed Uduman, John C Castle, Jennifer S. Buell, Jonathan C. Trent and Breelyn A. Wilky Journal for Immunotherapy of Cancer 2019 7:213.

HERTHENA-Lung01: A randomized phase 2 study of patritumab deruxtecan (HER3-DXd) in previously treated metastatic EGFR-mutated NSCLC.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. TPS9139-TPS9139
Author(s):  
Pasi A. Janne ◽  
Melissa L. Johnson ◽  
Yasushi Goto ◽  
James Chih-Hsin Yang ◽  
Michele Vigliotti ◽  
...  
Keyword(s):  
Phase 1 ◽  
Locally Advanced ◽  
Small Cell ◽  
Phase 2 ◽  
Platinum Based Chemotherapy ◽  
Phase 2 Study ◽  
Her3 Expression ◽  
Previously Treated ◽  
Epidermal Growth ◽  
Ongoing Phase

TPS9139 Background: Few treatment options have demonstrated therapeutic benefit in epidermal growth factor receptor–mutated ( EGFRm) non–small cell lung cancer (NSCLC) that has progressed after treatment with EGFR tyrosine kinase inhibitors (TKIs) and platinum-based chemotherapy. HER3, a member of the human epidermal growth factor family, is detectable in most EGFRm NSCLC, and its expression has been linked to worse clinical outcomes. There are no approved HER3 directed therapies for the treatment of NSCLC. HER3-DXd is a novel, potentially first-in-class HER3 directed antibody drug conjugate that has demonstrated preliminary evidence of safety and antitumor activity in patients (pts) with EGFRm TKI–resistant NSCLC in an ongoing Phase 1 study, providing proof of concept of HER3-DXd. The Phase 2 study (HERTHENA-Lung01) is further evaluating HER3-DXd in pts with previously treated metastatic or locally advanced EGFRm NSCLC. Methods: This randomized, open-label Phase 2 study will enroll up to 420 pts at approximately 135 study sites in North America, Europe and the Asia-Pacific region. Eligible pts will have metastatic or locally advanced NSCLC with an activating EGFR mutation (exon 19 deletion or L858R), progression during or after systemic treatment with ≥1 EGFR TKI and ≥1 platinum-based chemotherapy regimen, and ≥1 measurable lesion confirmed by blinded independent central review (BICR) per RECIST v1.1. Pts with an EGFR T790M mutation must have received and progressed on prior osimertinib. Pts with stable brain metastases are eligible. Exclusion criteria include evidence of previous small cell or combined small cell/non–small cell histology or any history of interstitial lung disease. Tumor tissue will be assessed retrospectively for HER3 expression and molecular mechanisms of TKI resistance. HER3 expression will not be used to select pts for enrollment. Pts will be randomized 1:1 to receive 1 of 2 HER3-DXd Q3W dose regimens that will be independently evaluated: a 5.6 mg/kg fixed-dose regimen (Arm 1) or an up-titration dose regimen (Arm 2: Cycle 1, 3.2 mg/kg; Cycle 2, 4.8 mg/kg; Cycle 3 and beyond, 6.4 mg/kg). After review of data from an ongoing Phase 1 study with similar patients treated with either of these dose regimens, a decision could be made to continue enrollment into 1 or both arms. The primary objective is to evaluate the efficacy of HER3-DXd as measured by objective response rate (ORR) by BICR. Secondary objectives are to evaluate the efficacy and safety/tolerability of HER3-DXd and to assess the relationship between efficacy and HER3 expression. Secondary endpoints include duration of response, progression-free survival, ORR by investigator, disease control rate, time to response, best percentage change in the sum of diameters of measurable tumors, and overall survival. The study is enrolling and is planned to finish in 2023. Clinical trial information: NCT04619004.

Efficacy of programmed death 1 (PD-1) and programmed death 1 ligand (PD-L1) inhibitors in patients with FGFR mutations and gene fusions: Results from a data analysis of an ongoing phase 2 study of erdafitinib (JNJ-42756493) in patients (pts) with advanced urothelial cancer (UC).

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 450-450 ◽  
Author(s):  
Arlene O. Siefker-Radtke ◽  
Andrea Necchi ◽  
Eli Rosenbaum ◽  
Stephane Culine ◽  
Earle Frederick Burgess ◽  
...  
Keyword(s):  
Response Rate ◽  
Gene Fusions ◽  
Phase 2 ◽  
Checkpoint Inhibition ◽  
Immune Checkpoint Inhibition ◽  
Programmed Death ◽  
Phase 2 Study ◽  
Programmed Death 1 ◽  
Fgfr3 Mutations ◽  
Ongoing Phase

450 Background: FGFR3 mutations appear to be enriched in luminal 1 UC, which have low expression of markers associated with an immune response, including CD8-T-effector gene expression levels. Objective response rate (ORR) to PD-1 and PD-L1 inhibitors in luminal 1 tumors appear lower (10-19%) than in infiltrated luminal 2 and basal 3 tumors (ORR 31-34%). This suggests FGFR3 mutations occur within a group of tumors less likely to benefit from immune checkpoint inhibition (ICI). Here we describe outcomes of a subgroup of pts with FGFR2/3 mutations and gene fusions, previously treated with PD-1/PD-L1 inhibitors and included in an ongoing erdafitinib phase 2 study. Methods: Patients who had received prior immunotherapy for advanced UC were selected from those enrolled on BLC2001, an ongoing phase 2, open-label study of the pan-FGFR inhibitor erdafitinib in subjects with advanced UC with specific FGFR2/3 gene alterations (NCT02365597). We explored investigator-reported clinical outcomes including ORR and median time to progression (TTP) of pts treated with ICI preceding erdafitinib therapy. Results: 28/203 pts had previously received anti PD-1 or anti PD-L1 treatment. In this subgroup, the median age was 67.0 y; 82% were male, 79% had an ECOG score ≤1, 36% had liver metastases, and 93% had ≥2 prior lines of systemic therapy. The response rate to anti PD-1/PD-L1 agents was 3.6% (95% CI, 0.1%-18.3%) with one partial response. Median TTP was 3.4 mo (range 2-15 mo; 95% CI, 2.3-4.9). Conclusions: In this post-hoc analysis, FGFR mutations and gene fusions seem to select for a group of pts less likely to respond to immune checkpoint inhibition. Although caution is needed due to the retrospective nature of the data, the presence of these alterations may reflect an unmet need with currently approved agents. This finding highlights the need for FGFR alteration testing and an effective FGFR-targeted therapy. Clinical trial information: NCT02365597.

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