Phase Ib/II study of pembrolizumab with lanreotide depot for advanced, progressive gastroenteropancreatic neuroendocrine tumors (PLANET).

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 369-369
Author(s):  
Michael Morse ◽  
Daniel M. Halperin ◽  
Hope Elizabeth Uronis ◽  
David S. Hsu ◽  
Herbert Hurwitz ◽  
...  
Keyword(s):  
External Beam Radiotherapy ◽  
Locoregional Therapy ◽  
Somatostatin Analogue ◽  
Antitumor Effects ◽  
Gastroenteropancreatic Neuroendocrine Tumors ◽  
Best Response ◽  
Secondary Endpoints ◽  
Clinical Trial Information ◽  
Experienced Treatment

369 Background: Pembrolizumab has antitumor activity in a subset of GEP-NETs patients. We hypothesized that the lanreotide, by its antitumor effects and reduction of serotonin, a modulator of immunity, would synergize with pembrolizumab in low/intermediate grade GEPNETs. Methods: GEP-NETs patients who had progressed on a prior somatostatin analogue received lanreotide 90mg sq and pembrolizumab 200mg IV every 3 weeks until progressive disease or intolerable toxicity. The primary endpoint was ORR at any time on study and secondary endpoints were PFS and OS. Results: 22 patients were treated (F/M 10/12; Caucasian/AA/other 10/7/5; GI/pancreatic 14/8; median Ki67 5%, median time since diagnosis 5.3 yrs (IQR 2.3-7.9 yrs)). Prior octreotide LAR/lanreotide/both was administered to 20/1/1. Patients had a median of 2 prior systemic therapies (range 1-9) and six had prior locoregional therapy and 3 external beam radiotherapy. Of the 12 tumors analyzed thus far, 4 had detectable PD-L1 expression and 11 had detectable TILs. A median of 6 pembrolizumab doses (range 2-15) and 7 lanreotide doses (range 2-15) were administered. Six patients experienced treatment related SAEs (abdominal pain, pneumonitis, colitis, and hyperglycemia, all related to the pembrolizumab). Selected treatment related adverse events included: Hypothyroidism 23%, colitis 9%, hyperglycemia 14%, and pneumonitis 5%. Best response by RECIST 1.1 was SD/PD/Not available:39/52/9% and by irRECIST was 43/48/9%. Median PFS was 5.4 months (95% CI 1.7-8.3 mo). The median overall survival at a median follow-up of 15 months was not reached. Peripheral blood immunologic correlates will be reported subsequently. Conclusions: In a population of GEP-NET patients, progressing on a median of 2 prior therapies, including prior somatostatin analogue therapy, a minority of whom had PD-L1 expressing tumors, the combination of lanreotide and pembrolizumab produced stable disease in approximately 40% of patients. No new safety signals were identified. Clinical trial information: NCT03043664.

Results of a phase II trial of docetaxel (DOC), bevacizumab (BEV), and androgen deprivation therapy (ADT) for biochemical relapse (BCR) after definitive local therapy for prostate cancer (PC).

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 54-54
Author(s):  
Rana R. McKay ◽  
Kathryn P. Gray ◽  
Julia H. Hayes ◽  
Glenn J. Bubley ◽  
Jonathan E. Rosenberg ◽  
...  
Keyword(s):  
Specific Antigen ◽  
Local Therapy ◽  
Primary Treatment ◽  
Entire Cohort ◽  
Psa Response ◽  
Secondary Endpoints ◽  
Psa Progression ◽  
Grade 3 ◽  
Clinical Trial Information

54 Background: Despite primary treatment for localized PC, 20-30% of men experience a BCR, detected by a rise in prostate-specific antigen (PSA). Though 30% of these patients develop metastatic disease, the optimal treatment of men with BCR has yet to be determined. In this trial, we evaluate the efficacy of DOC, BEV, and ADT for men with BCR after local therapy for PC. Methods: 41 men with a BCR and PSA doubling time of ≤10 months (mos) were enrolled. Patients received 4 cycles of DOC (75 mg/m2) every 3 weeks, 8 cycles of BEV (15 mg/kg) every 3 weeks, 18 mos of a luteinizing-hormone releasing hormone (LHRH) agonist, and 15 mos of bicalutamide (50 mg daily) beginning after completion of DOC. The primary endpoint was the proportion of patients free from PSA-progression 1 year after completion of ADT. Secondary endpoints included PSA response, testosterone recovery, and toxicity. Results: Median follow-up was 27.6 mos. Median age at diagnosis was 58 years. Median PSA at diagnosis was 6.7 ng/mL, with the majority of patients (59%) having Gleason 7 disease. Most patients underwent radical prostatectomy +/- radiation therapy (n=36). At baseline, 33 men (81%) had a normal testosterone (> 240 ng/dL). The table describes the PSA responses for the entire cohort. 10 men (28%) had a normal testosterone 6 mos after completing ADT. 17 men (47%) had a normal testosterone 12 mos after completing ADT, of whom 5 (29%) had a PSA <0.2 ng/mL at that time. There were 15% grade 1, 34% grade 2, 39% grade 3, and 12% grade 4 adverse events (AEs). The most frequent grade 3-4 AEs included neutropenia (24%), febrile neutropenia (11%), and hypertension (9%). Conclusions: DOC, BEV, and ADT for BCR resulted in complete responses in 16 men (44%) 1 year after completion of therapy. Longer follow-up is needed to determine the efficacy of this regimen. Clinical trial information: NCT00658697. [Table: see text]

Single agent ONC201 in adult recurrent H3 K27M-mutant glioma.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 3005-3005
Author(s):  
Isabel Arrillaga ◽  
Sylvia Kurz ◽  
Ashley Sumrall ◽  
Nicholas A. Butowski ◽  
Rebecca A. Harrison ◽  
...  
Keyword(s):  
Stable Disease ◽  
Poor Prognosis ◽  
Progressive Disease ◽  
Tumor Regression ◽  
Single Agent ◽  
Complete Regression ◽  
Compassionate Use ◽  
Best Response ◽  
Clinical Trial Information

3005 Background: H3 K27M-mutant glioma is associated with a poor prognosis and there is no effective therapy following radiation. We report the clinical experience with single agent ONC201, the first small molecule DRD2 antagonist in oncology, in adults with recurrent H3 K27M-mutant glioma. Methods: Twenty-nine adult patients with recurrent H3 K27M-mutant glioma have been treated with single agent ONC201 as of January 20, 2019: 19 patients on NCT03295396; 8 patients on NCT02525692; 2 patients on compassionate use protocols under the Sponsor’s IND. Median age was 57 years old (range: 17-74), median prior lines of therapy was 2 (range: 1-4) and all patients received prior radiation (median 8.5 months from radiation completion to ONC201 initiation). ONC201 was orally administered at 625 mg weekly, except for one patient dosed once every 3 weeks. Results: As of February 5, 2019, 13 of 29 patients remain on-trial within median follow up of 6.5 months (range: 0.6-33.6), 8 patients are alive but off-trial with median follow up of 2.4 months (range: 0.2-9), and 8 patients have expired. Nine of 29 patients (31%) remain progression-free on ONC201 with a median follow up of 6.5 months (range 0.6-33.6). No dose-limiting toxicities or treatment discontinuations due to toxicity occurred. Three patients have experienced durable partial responses by RANO (4.3-28.5 months). In addition, one patient experienced complete regression that continues for > 14 months of all < 1 cm tumor lesions that are not measurable by RANO. Furthermore, 10 patients had a best response of stable disease by RANO, 12 patients experienced progressive disease, and 3 patients are not yet evaluable. Among the patients with a best response of stable disease by RANO, one patient had > 50% tumor regression in the basal ganglia that did not qualify as a partial response by RANO due to a new lesion on a confirmatory scan. Another patient with stable disease by RANO has had 37% tumor regression so far in the brainstem and remains on-treatment for 6 months. All tumor regressions remain durable to date and some were associated with improvements in disease-associated neurological symptoms. Conclusions: Single agent ONC201 is well tolerated and clinically active in adult recurrent H3 K27M-mutant glioma patients. Clinical trial information: NCT03295396; NCT02525692.

Randomized phase IIb clinical trial of continuation or non-continuation with six cycles of temozolomide after the first six cycles of standard first-line treatment in patients with glioblastoma: A Spanish research group in neuro-oncology (GEINO) trial.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 2001-2001
Author(s):  
Carmen Balana ◽  
Carlos Mesia Barroso ◽  
Sonia Del Barco Berron ◽  
Estela Pineda Losada ◽  
José Muñoz-Langa ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Residual Disease ◽  
First Line ◽  
Newly Diagnosed Glioblastoma ◽  
Secondary Endpoints ◽  
Spanish Research ◽  
Clinical Trial Information

2001 Background: The GEINO-14-01 trial (NCT02209948) investigated the role of extending temozolomide (TMZ) for 6 cycles after the standard 6 cycles to improve 6m-PFS, SLP and OS in newly diagnosed glioblastoma (GBM) patients (p). Methods: Between 08/2014 and 11/2018, 166 p were screened and 159 randomized to extend (80p) or not (79p) TMZ treatment for 6 cycles after proving stable disease in the MRI performed before inclusion. Centralized review of histology and determination of MGMT status, if not previously available, were performed before randomizing patients. Two criteria of stratification were used: MGMT status and presence/absence of residual disease on the basal MRI (defined as a residual enhancement larger than 1cm in one). The primary endpoint was differences in 6mPFS, secondary endpoints were differences in PFS, OS, toxicity, between arms and per stratification factors. Results: Median age was 60.3 (range 29-83), 97p (61%) were methylated, basal MRI showed residual disease in 57p (35.8%). After a median follow up of 14.0 months, with 121 p(76.1%) already progressed and 81p (50.9%) already dead, median PFS is presented. Median (m) PFS is 8.0 months (95%CI: 5.7-10.2). There is no difference in mPFS between arms (adjusted HR = 0.98, 95% CI: 0.82-1.18, P = 0.907). Methylated tumors had longer mPFS (HR=0.57, 95% CI: 0.39-0.83, P=0.004) irrespectively to the study treatment. Conclusions: There is not apparent benefit of continuing TMZ treatment for more than 6 cycles. Data will be actualized for the congress.Supported by a Grant of the ISCIII: PI13/01751. Clinical trial information: NCT02209948.

Effects of radium-223 dichloride (Ra-223) with docetaxel (D) versus D on prostate-specific antigen (PSA) and bone alkaline phosphatase (bALP) in patients (pts) with castration-resistant prostate cancer (CRPC) and bone metastases (mets): A phase 1/2a clinical trial.

2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 202-202 ◽  
Author(s):  
Michael J. Morris ◽  
Celestia S. Higano ◽  
Howard I. Scher ◽  
Christopher Sweeney ◽  
Emmanuel S. Antonarakis ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Phase 1 ◽  
Specific Antigen ◽  
Bone Alkaline Phosphatase ◽  
Serum Markers ◽  
Castration Resistant Prostate Cancer ◽  
Antitumor Effects ◽  
Radium 223 ◽  
Best Response

202 Background: Ra-223 is an approved α-emitter prolonging survival in CRPC with symptomatic bone mets. We conducted a phase 1/2a study examining the safety and antitumor effects of Ra-223 + D vs D alone, and previously presented data showing that Ra-223 + D is safe and well tolerated (ESMO 2014). Here we report the effect of Ra-223 + D vs D on bALP and PSA dynamics. Methods: D-eligible pts with progressing CRPC and ≥ 2 bone mets were randomized 2:1 to Ra-223 (50 kBq/kg q 6 wk × 5) + D (60 mg/m2 q 3 wk × 10) vs D (75 mg/m2 q 3 wk with step-down option to 60 mg/m2). bALP and PSA were recorded q 3 wk during first 6-wk cycle, then q 6 wk and q 3 wk, respectively, and analyzed at a central laboratory. Changes in both markers are described by the % of pts who achieved ≥ 30%, > 50%, and > 80% declines between baseline and the safety follow-up visit (3 wk post last D injection) as their best response; pts with elevated baseline bALP (≥ 21 µg/L) levels were included for the bALP analysis. bALP to below the upper limit of normal (ULN) was also recorded, regardless of % decline. Results: 46 pts (33 Ra-223 + D vs 13 D alone) were enrolled. As of October 2014, 21 (Ra-223 + D) vs 5 (D) pts had received all planned study treatment. Median (range) baseline PSA was 99 µg/L (3-1000) for Ra-223 + D pts and 43 µg/L (4-1042) for D pts. Maximal changes in PSA and bALP levels between baseline and safety follow-up are shown in Table. No pt had a bALP increase. Conclusions: Ra-223 + D appears to favorably impact posttreatment PSA and bALP declines. Ra-223 + D appears particularly effective at normalizing bALP levels vs D alone. The clinical benefits of such changes in serum markers will require validation in larger prospective studies. Clinical trial information: NCT01106352. [Table: see text]

Brigatinib (BRG) in patients (pts) with crizotinib (CRZ)-refractory ALK+ non-small cell lung cancer (NSCLC) and brain metastases in the pivotal randomized phase 2 ALTA trial.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e20502-e20502 ◽  
Author(s):  
Sai-Hong Ignatius Ou ◽  
Marcello Tiseo ◽  
D. Ross Camidge ◽  
Myung-Ju Ahn ◽  
Rudolf M. Huber ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Review Committee ◽  
Small Cell Lung ◽  
Best Response ◽  
Independent Review ◽  
Grade 3 ◽  
A Site ◽  
To Receive ◽  
Clinical Trial Information

e20502 Background: The CNS is often a site of first disease progression in CRZ-treated ALK+ NSCLC. The ALTA trial is assessing BRG, an investigational next-generation ALK inhibitor, in pts with CRZ-refractory advanced ALK+ NSCLC, including pts with baseline brain metastases. Methods: In ALTA (NCT02094573), pts were stratified by presence of baseline brain metastases and best response to prior CRZ and randomized 1:1 to receive BRG at 90 mg qd (arm A) or 180 mg qd with a 7-d lead-in at 90 mg (arm B). Here, we show data for pts with baseline brain metastases. An independent review committee (IRC) assessed intracranial efficacy. Results: Of 222 pts (112 in arm A; 110 in arm B), 80 (71%)/74 (67%) in A/B had baseline brain metastases per investigators, with median age 49/55 y; 74%/76% had received chemotherapy. As of May 31, 2016, 51%/59% of these pts continued to receive BRG in A/B; median follow-up was 9.6/11.4 mo. Intracranial efficacy is shown in the table. Among these pts, most common treatment-emergent adverse events were: nausea 35%/46% (A/B), headache 30%/31%, vomiting 29%/31%, diarrhea 21%/38%, cough 25%/32%; grade ≥3: increased blood CPK 1%/12%, hypertension 4%/7%, increased lipase 4%/3%. Conclusions: BRG yielded substantial intracranial responses with robust iPFS and acceptable safety in ALK+ NSCLC pts with baseline brain metastases in ALTA. 180 mg (with lead-in) showed consistently improved intracranial efficacy compared with 90 mg. Clinical trial information: NCT02094573. [Table: see text]

Confirmed three-year RFS and OS of the randomized trial of adjuvant S-1 versus S-1 plus docetaxel after curative resection of pStage III gastric cancer (JACCRO GC-07).

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 159-159
Author(s):  
Kazuhiro Yoshida ◽  
Yasuhiro Kodera ◽  
Mitsugu Kochi ◽  
Takeshi Sano ◽  
Yoshihiro Kakeji ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Controlled Trial ◽  
D2 Gastrectomy ◽  
Secondary Endpoints ◽  
To Receive ◽  
Computerized System ◽  
Safety Monitoring Committee ◽  
Clinical Trial Information ◽  
Docetaxel Group

159 Background: JACCRO GC-07 is a randomized controlled trial to explore postoperative S-1/docetaxel compared to S-1 alone after D2 gastrectomy for pStage III gastric cancer (GC) patients. The second interim analysis demonstrated that the significant improvement of RFS was obtained by S-1/docetaxel compared to S-1 alone. The study was terminated by the recommendation of independent data and safety monitoring committee and the results were reported at ASCO 2018 and published in the Journal of Clinical Oncology (Yoshida K et al. 2019; 37:1296-1304). As 3 years have passed after completion of the enrollment, preplanned analysis was performed with the updated information of the patients. Methods: Patients with pStage III GC were randomly assigned to receive either S-1/docetaxel (S-1 80-120mg/body on days 1-14 with a 7-day rest followed by docetaxel 40mg/m2 on day 1 and S-1 80-120mg/body on days 1-14 every 21 days for 6 cycles followed by S-1 80-120mg/body on days 1-28 every 42 days for 4 cycles) or S-1 (80-120mg/body on days 1-28 every 42 days for 8 cycles) after D2 gastrectomy. Block randomization was performed by a central interactive computerized system stratified by the stage (IIIA, IIIB, IIIC) and histological type (differentiated or undifferentiated). The sample size of 1,100 was necessary to detect a 7% increase in the 3-year RFS. The primary endpoint was 3y RFS and the secondary endpoints were OS, TTF and safety. Results: In the present analysis, 400 recurrences and 324 deaths were confirmed among 912 patients during the median follow-up period of 42.5 months (0.3-85.16). The 3y RFS of 67.7% in the S-1/docetaxel group was significantly superior to 57.4% in the S-1 group (HR 0.715, 95% CI: 0.587-0.871, p = 0.0008) and the 3y OS was 77.7% in the S-1/docetaxel group and that of S-1 group was 71.2%, respectively (HR 0.742, 95% CI: 0.596-0.925, p = 0.0076), confirming the significant improving effect on the survival of the patient. Conclusions: Adjuvant S-1 plus docetaxel is recommended for patients with pStage III gastric cancer who underwent D2 gastrectomy without neoadjuvant chemotherapy. Clinical trial information: UMIN 000010337.

Prognostic impact of changes in circulating tumor cells (CTC) in metastatic breast cancer (MBC).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 11012-11012
Author(s):  
Markus Wallwiener ◽  
Andreas D. Hartkopf ◽  
Sabine Riethdorf ◽  
Martin Sprick ◽  
Christoph Wolfram Domschke ◽  
...  
Keyword(s):  
Prognostic Value ◽  
Progressive Disease ◽  
Tumor Response ◽  
Metastatic Breast ◽  
Prognostic Impact ◽  
Best Response ◽  
Line Of Therapy ◽  
Age Range ◽  
Clinical Trial Information

11012 Background: To prospectively assess the prognostic value of CTC counts at baseline and after one cycle of therapy and their kinetics for response, progression-free (PFS), and overall survival (OS) in MBC. Methods: MBC patients underwent CTC enumeration (CellSearch, Veridex) at baseline (CTCBL), after one cycle of a new line of therapy (CTC1C), and at progression (CTCPD). CTC status was classified as negative (neg (−)) or positive (pos (+)) for <5 and ≥5 CTC/7.5 ml peripheral blood, respectively. CTC kinetics (CTCKIN) from CTCBL to CTC1C were classified as favorable if CTCs remained neg (neg>neg) or became neg (pos>neg), or as unfavorable (neg>pos or pos>pos). Tumor response was assessed every 2–3 months using RECIST criteria. CTC status and kinetics were associated with outcome using log-rank and Fisher’s exact tests. Results: Of 326 patients enrolled (median age (range) at first diagnosis: 50 (23–81) years), 115/326 (35%) were CTCBL+, 51/162 (31%) were CTC1C+, and 39/108 (36%) were CTCPD+. Median follow-up was 15.9 months (mos). Median PFS and OS were significantly reduced in CTCBL+ compared to CTCBL− patients (PFS, 4.3 vs. 7.1 mos, p = .019; OS, 15.0 mos vs. not reached (nr), p <.001) and for CTC1C+ compared to CTC1C− patients (p <.001 for PFS and OS). CTCKIN were predictive of progressive disease as best response (neg>neg, 33%; pos>neg, 38%; pos>pos, 60%; neg>pos, 75%; p = .040). PFS and OS for patients with unfavorable CTCKIN were significantly shorter than for favorable CTCKIN (PFS, 3.7 vs. 6.8 mos, p <.001; OS, 7.8 mos vs. nr, p <.001). Conclusions: CTC at baseline, CTC after one cycle and CTC kinetics are highly predictive of outcome in MBC. Serial CTC enumeration could serve as a useful adjunct to standard diagnostic tests in tailoring therapy. Further details of CTCPD will be presented at the meeting. Clinical trial information: S-295/2009.

A multicenter phase II study of venetoclax plus dose-adjusted R-EPOCH (VR-EPOCH) for Richter’s syndrome.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 8004-8004 ◽  
Author(s):  
Matthew Steven Davids ◽  
Kerry Anne Rogers ◽  
Svitlana Tyekucheva ◽  
Samantha Pazienza ◽  
Sarah K Renner ◽  
...  
Keyword(s):  
Influenza A ◽  
Single Agent ◽  
Phase 2 ◽  
Best Response ◽  
Pet Ct ◽  
Phase 2 Study ◽  
Clinical Trial Information ◽  
Count Recovery ◽  
Richter’S Syndrome

8004 Background: While therapeutic options for CLL have improved, patients (pts) who develop Richter’s Syndrome (RS) still have a poor prognosis. Chemoimmunotherapy regimens such as R-EPOCH lead to CR in about 20% of RS pts, but PFS/OS is typically < 6 mo. The oral Bcl-2 inhibitor venetoclax (ven) had a 43% single agent response rate in RS. Here, we report the results of a phase 2 study of VR-EPOCH in RS. Methods: This is a single-arm, phase 2, IST of VR-EPOCH for RS (NCT03054896) at 3 US sites. CLL pts with biopsy-confirmed DLBCL were treated with R-EPOCH for 1 cycle, then after count recovery underwent accelerated inpatient ven daily ramp-up (20/50/100/200/400 mg), then ven + R-EPOCH for up to 5 more 21d cycles (ven 400 mg qd, d1-10 each cycle). Responders went to alloHCT or to continuous daily ven 400 mg maintenance. Response evaluation by Lugano criteria with PET/CT. Results: As of the data cut on 2/3/2020, the study is fully enrolled with 27 pts. Median age: 63 yrs (range 49-77). CLL features: 26% del(17p); 44% complex karyotype; 48% IGHV unmutated; 41% TP53 and 15% NOTCH1 mutation. Median prior CLL treatments: 2 (range 0-5, prior ibrutinib [n = 8], ven [n = 2], and PI3Ki [n = 2]) with 6 untreated CLL pts. Median # ven + R-EPOCH cycles: 4 (range 0-6). 5 pts had dose de-escalation of R-EPOCH, 1 pt had dose escalation. ≥Gr 3 heme tox: neutropenia (58%), anemia (50%), thrombocytopenia (50%). ≥Gr 3 non-heme tox in > 15% of pts: febrile neutropenia (38%) and hypophosphatemia (23% each). No pts had TLS with daily ven ramp-up. Infections: pneumonia (n = 4), sepsis during C1 of R-EPOCH prior to starting ven (n = 3), enterocolitis (n = 3), sinusitis (n = 2), and 1 pt each with influenza A and norovirus. 10 pts have died, including 7 due to disease progression (2 during C1 before ven), and 1 each due to sepsis, sudden death, and GVHD post-alloHCT. In ITT analysis, 16 responded (ORR 59%); 13/27 (48%) had CR as best response, all with undetectable bone marrow MRD for CLL. Six pts were not evaluable for efficacy of the combo (5 had toxicity in C1 and never started ven, 1 withdrew after C1). In the 21 pts who started combo therapy, the ORR was 76%, CR rate 62%. Only 1 pt with CR has progressed. The pt on longest ven maintenance is in CR 2 years post chemo. 8 pts went to alloHCT, with pts still in CR now up to 2.5 yrs post-alloHCT. With a median follow-up of 9.3 mo (range 0.6-30), median PFS and OS are both 16.3 mo. Conclusions: VR-EPOCH is active for RS. Expected toxicities from intensive chemoimmunotherapy and ven were seen, but daily ven ramp-up was feasible. The 48% CR rate and median PFS of 16.3 mo are favorable in the context of historical results. Clinical trial information: NCT03054896 .

Optimized management of nivolumab (Nivo) and ipilimumab (Ipi) in advanced renal cell carcinoma (RCC): A response-based phase II study (OMNIVORE).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 5005-5005 ◽  
Author(s):  
Rana R. McKay ◽  
Wanling Xie ◽  
Bradley Alexander McGregor ◽  
David A. Braun ◽  
Xiao X. Wei ◽  
...  
Keyword(s):  
Phase Ii ◽  
Complete Response ◽  
Poor Risk ◽  
Best Response ◽  
Primary Endpoints ◽  
Sequential Addition ◽  
Grade 3 ◽  
Induce Response ◽  
Clinical Trial Information

5005 Background: Nivo + Ipi is an established first-line treatment (tx) for advanced RCC. We hypothesized that the addition of CTLA-4 blockade may not be required for all patients (pts). Furthermore, the optimal duration of Nivo maintenance in responding pts is unknown. In this phase II response-adaptive trial, we investigate the sequential addition of 2 doses of Ipi to induce response in Nivo non-responders (NR) and duration of Nivo in responding pts (NCT03203473). Methods: We enrolled pts with advanced RCC with no prior checkpoint inhibitor exposure. All pts received Nivo alone with subsequent arm allocation based on RECISTv1.1 response within 6 months (mos) of tx. Pts with a confirmed partial response (PR) or complete response (CR) within 6 months (mos) discontinued Nivo and were observed (Arm A). Arm A pts reinitiated Nivo if they developed progressive disease (PD); Ipi was added to Nivo if PD persisted or recurred. Pts with stable disease (SD) or PD after no more than 6 mos of Nivo alone received 2 doses of Ipi (Arm B). The primary endpoints were the proportion with PR/CR at 1-year (yr) after Nivo discontinuation (Arm A) and proportion of Nivo NR who convert to PR/CR after adding Ipi (Arm B). Results: 83 pts initiated tx of whom 99% had ECOG 0-1, 96% clear cell RCC, 51% tx-naïve, and 69% IMDC intermediate/poor risk. Median follow-up was 17.0 mos. 15 pts were not allocated to an arm [7 withdrew for PD, 7 withdrew for toxicity, 1 still on tx with unconfirmed PR (uPR)]. At 6 mos, induction Nivo resulted in a confirmed PR in 11% of pts (n=9/83): 12% (n=5/42) tx-naïve, 10% (4/41) prior tx, 8% (n=1/13) favorable risk, 11% (n=8/70) intermediate/poor risk (Table). 11 pts (13%: 9 PR, 1 uPR, 1 SD) were allocated to Arm A, of whom 5 (45%, 90% CI 20-73%) remained off Nivo at ≥ 1 yr. Of 57 pts (69%) allocated to Arm B, 2 pts converted to a PR (4%, 90% CI 1-11%), both of whom had prior tx and PD as best response to Nivo alone. Grade 3-4 treatment related adverse events (TrAE) occurred in 7% (n=6/83) on induction Nivo and in 23% (n=13/57) on Arm B (Nivo + Ipi). Conclusions: We cannot currently recommend a strategy of Nivo followed by response-based addition of Ipi due to the absence of CR and low PR/CR conversion rate (4%). Though a subset of pts treated with Nivo alone can maintain durable responses off tx at 1-yr, early Nivo discontinuation in the absence of toxicity cannot currently be recommended. Investigation into biomarkers to guide tx is ongoing. Clinical trial information: NCT03203473 . [Table: see text]

Clinical efficacy of ONC201 in thalamic H3 K27M-mutant glioma.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 3617-3617
Author(s):  
Abed Rahman Kawakibi ◽  
Rohinton Tarapore ◽  
Sharon L. Gardner ◽  
Sylvia Christine Kurz ◽  
Patrick Y. Wen ◽  
...  
Keyword(s):  
Clinical Efficacy ◽  
Single Agent ◽  
Line Radiation ◽  
Primary Tumors ◽  
Best Response ◽  
Duration Of Response ◽  
Post Radiation ◽  
The Brain ◽  
Clinical Trial Information

3617 Background: Diffuse midline gliomas, H3 K27M-mutant are associated with a poor prognosis compared to H3 wild-type gliomas and have no effective therapy following first-line radiation. ONC201 is a bitopic DRD2 antagonist and allosteric ClpP agonist that has shown encouraging single agent efficacy in recurrent H3 K27M-mutant gliomas located in various midline structures of the brain. In addition to tumor and immune cells, the pharmacodynamics of ONC201 extend to stromal cells that can mediate a bystander antitumor response in preclinical models. Given this observation and that the thalamus has the highest extrastriatal expression of DRD2, we report the clinical experience of ONC201 in a subgroup of H3 K27M-mutant glioma patients with primary tumors located in the thalamus. Methods: We analyzed 29 thalamic H3 K27M-mutant glioma patients treated with ONC201 in clinical trials enrolled as of 5/22/19. Nineteen enrolled with recurrent disease whereas 10 enrolled following radiation prior to recurrence. Twelve patients enrolled on NCT03295396, 10 NCT03416530, 4 NCT02525692, and 3 expanded access. Median age was 22 years old (range: 5-70) and baseline KPS was 80 (range: 60-90). Median time from radiation to start of ONC201 was 1.8 months (range: 0.2-8.7) for non-recurrent patients and 7.2 months (range: 1.4-102.0) for recurrent patients. Results: As of 12/18/2019, PFS6 and OS12 measured relative to initiation of ONC201 are 26.3% and 36.8%, respectively, in the recurrent group. For patients initiating ONC201 post-radiation prior to recurrence, median PFS or OS have not been reached with a median follow up of 21.9 months (8.6-26.6) from diagnosis, which surpass historical OS of 13.5 months. Best response for evaluable recurrent patients by RANO: 1 CR, 3 PR, 4 SD, 8 PD, 3 not reported; for non-recurrent patients: 2 PR, 4 SD, 1 PD, 3 not reported. Median duration of response for recurrent patients is 14.0 months (2.0-33.1). ONC201 was well tolerated and no dose-limiting toxicities or treatment discontinuations due to toxicity occurred. Furthermore, H3 K27M cell-free tumor DNA in plasma and CSF correlated with MRI response. Conclusions: In summary, single agent ONC201 administered at recurrence or following radiation, demonstrates promising clinical efficacy in thalamic H3 K27M-mutant glioma patients. Investigations are ongoing to assess whether micro-environmental DRD2 expression correlates with responses of thalamic H3 K27M-mutant glioma to ONC201. Clinical trial information: NCT03295396, NCT03416530, NCT02525692 .

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