Phase 1b/2, open label, multicenter study of intratumoral SD-101 in combination with pembrolizumab in anti-PD-1 treatment naïve patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 6039-6039 ◽  
Author(s):  
Ezra E.W. Cohen ◽  
Lisle Nabell ◽  
Deborah J.L. Wong ◽  
Terry A Day ◽  
Gregory A. Daniels ◽  
...  
Keyword(s):  
Ct Scan ◽  
Open Label ◽  
Primary Tumors ◽  
Ifn Alpha ◽  
Hpv Status ◽  
Treatment Naïve ◽  
Grade 3 ◽  
Ecog Ps ◽  
Antigen Presenting

6039 Background: SD-101, a synthetic CpG-ODN agonist of TLR9, stimulates dendritic cells to release IFN-alpha and mature into antigen presenting cells - activating T cell anti-tumor responses. Pembrolizumab has demonstrated activity in HNSCC. Study DV3-MEL-01 (NCT02521870) assesses safety and efficacy of SD-101 in combination with pembrolizumab in patients with recurrent/metastatic HNSCC. We have previously reported a 27.3% ORR in 22 patients receiving 8 mg SD-101/injection in the modified ITT after at least 2 CT scans due to late responses (Abstract 3560, ESMO 2018). Higher efficacy at a lower SD-101 dose, 2 mg/injection, has been reported in advanced melanoma patients (LBA 45, ESMO 2018). Consequently, this dose is now being assessed in HNSCC. We report preliminary data with the 2 mg/injection dose in 23 patients in mITT at the first CT scan. Methods: Anti-PD-1/PD-L1 naïve patients received 2 mg SD-101 intratumorally in 1 - 4 lesions (weekly x 4 doses then Q3W x 7 doses). Pembrolizumab is was administered IV at 200 mg Q3W. Responses were assessed per RECIST v1.1. Results: 28 patients enrolled: median age 63 y/o, male 68%; ECOG PS 0-1 (18%/82%); mean prior lines of systemic therapy 1 (0-3); mean treatment duration 70 days (1-253). Primary tumors: 19 (68%) oropharyngeal; 3 (10%) laryngeal; 2 (7%) hypopharyngeal; 4 (14%) unknown. Mean number of target lesions: 1.82 (1 to 5). HPV status: 7 (25%) +, 9 (32%) -, 12 (43%) unknown. 18 (64 %) discontinued treatment: 12 (42%) due to PD, 4 (16%) deaths, 1 (3%) consent withdrawn, 1 (3%) went to hospice. Mean follow up 2.70 months. Safety: 16 non-treatment-related SAEs in 9 patients. 2 treatment-related Grade ≥3 AEs: sepsis (4%) and lymphopenia (4% ). No treatment-related deaths. Efficacy: 23 patients in the mITT population with first CT scan at day 64: ORR: CR: 2, PR: 3 (22%); SD: 6 (26%), PD: 7 (30%), non-evaluable: 5 (22%). Disease control rate (48%). 5 patients on study have not had a CT scan. Conclusions: SD-101 with Pembrolizumab shows early promising data and is well tolerated. Additional follow-up scans from both dose cohorts are being evaluated and will be presented. Clinical trial information: NCT02521870.

Phase 1b/2, open label, multicenter, study of the combination of SD-101 and pembrolizumab in patients with advanced/metastatic melanoma resistant to anti-PD-1/PD-L1 therapy.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 9555-9555 ◽  
Author(s):  
Asim Amin ◽  
Mohammed M. Milhem ◽  
Georgina V. Long ◽  
Christopher J. Hoimes ◽  
Theresa Michelle Medina ◽  
...  
Keyword(s):  
Ct Scan ◽  
Phase 2 ◽  
Open Label ◽  
Prior Therapy ◽  
Phase 2 Trial ◽  
Ifn Alpha ◽  
Unresectable Stage ◽  
Injection Methods ◽  
Grade 3 ◽  
Antigen Presenting

9555 Background: SD-101 is a synthetic CpG-ODN agonist of TLR9 that stimulates dendritic cells to release IFN-alpha and mature into antigen presenting cells - activating T cell anti-tumor responses. Pembrolizumab has demonstrated activity in melanoma. SYNERGY-001/KEYNOTE-184 study assesses the safety and preliminary efficacy of the combination of intratumoral SD-101 and intravenous pembrolizumab in PD1/PDL 1 resistant unresectable stage IIIC- IV melanoma. A prior phase 2 study with SD-101 at 8 mg per injection resulted in a 21.4% ORR in this population (Abstract 3781, ESMO 2018). We report preliminary data in this ongoing phase 2 trial evaluating efficacy at a lower SD-101 dose of 2 mg per injection. Methods: PD1/PDL 1 resistant melanoma patients received 2 mg of SD-101 intratumorally per lesion in 1-4 lesions (weekly x 4 doses followed by Q3W x 7). Pembrolizumab was administered at a dose of 200 mg intravenously Q3W. Scans were performed Q9W. Responses were assessed per RECIST v1.1. Results: 23 patients have been enrolled with baseline characteristics: median age 65 years; male: 77%; stage at screening: IIIC = 26%; IV = 57%, unknown = 17%; LDH > ULN: 36%. Lines of prior therapy: 1: 52%; 2: 22%; > 2: 26%. Prior anti CTL-A4 therapy: 39%. Best overall response on prior antiPD-1/PD-L1: PD: 88%, PR/CR: 8%, SD: 4%. Safety: Grade ≥3 treatment-related AEs: pneumonia and constipation (8%). No immune-related AEs reported. 2 non-treatment related SAEs reported from 2 patients: pneumonia and intussusception. 4 patients discontinued treatment early: 1 post SAE, per patient’s request, 3 due to PD. 1 patient died due to malignant pleural effusion after 1 dose of SD 101 and Pembrolizumab. No treatment related deaths. Efficacy: Mean duration on treatment: 39 days (1 - 169). mITT population: six patients at time of first CT scan at day 64: PR: 1, SD: 1, PD:3; non-evaluable: 1. 17 patients on study have not yet had first CT scan. Conclusions: The TLR9 innate immune stimulant, SD-101, in combination with pembrolizumab is well tolerated. Mature efficacy data, with additional first and second follow-up CT scans, will be presented at the meeting. Clinical trial information: NCT02521870.

A single-arm, open-label, U.S. expanded access study of vemurafenib in patients with metastatic melanoma.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 8567-8567
Author(s):  
Lynn Mara Schuchter ◽  
Lawrence E. Flaherty ◽  
Omid Hamid ◽  
Gerald P. Linette ◽  
Sigrun Hallmeyer ◽  
...  
Keyword(s):  
Metastatic Melanoma ◽  
Response Rate ◽  
Phase Iii ◽  
Open Label ◽  
Expanded Access ◽  
Treatment Naïve ◽  
Phase Iii Study ◽  
Prior Systemic Therapy ◽  
Ecog Ps

8567 Background: Vemurafenib (vem) has been FDA approved for the treatment of unresectable or metastatic BRAFV600E mutated melanoma since August 2011 based on results of a randomized phase III study (treatment-naive) and a single arm phase II study (previously treated). We report results of an expanded access study that allowed appropriate patients (pts) to receive vem until the drug was approved. Methods: Eligible pts had metastatic melanoma with a BRAFV600E mutation as detected by the cobas 4800 BRAFV600 Mutation Test. Enrolled pts received oral vem 960 mg b.i.d. Adverse events (AEs) were evaluated for vem-related toxicities; tumor responses were assessed using RECIST 1.1. Results: 29 US sites screened 745 pts and enrolled 374 from December 2010 until October 2011. The following results are based on a median follow up time and treatment duration of 2 months. At baseline, mean age of pts was 54 y with 22% of pts ≥65 y; 75% had stage M1c disease; 29% had received radiotherapy for brain metastases. 19% of pts were ECOG PS 2 or 3; 71% of pts had prior systemic therapy for metastatic melanoma (21% 1 regimen; 50% ≥2 regimens). 50 pts had prior adjuvant treatment. At data cut-off, 243 pts had sufficient follow-up time for tumor assessment. In this group, the unconfirmed overall response rate was 52% (95% CI, 46 to 59). The median time to response was 1.8 months. Based on 240 pts with available ECOG PS status at time of analysis, response rate was 53% for pts with ECOG PS 0 or 1 (n=209), and 45% for pts with ECOG PS 2 or 3 (n=31). 370 pts were evaluable for safety analysis. The most common vem-related AEs were rash (36%), arthralgia (33%) and fatigue (21%) with the majority (~90%) of grade 1 or 2. 25 vem-related serious AEs were reported in 5.4% of pts with a slightly higher rate of pts with ECOG PS 2 or 3 (8.7%) compared to ECOG PS 0 or 1 (4.7%). 18% of pts missed at least one dose and 11% of pts required dose reduction of at least one level due to AEs. Conclusions: This expanded access study, with its limited follow-up time, confirms the established rapid and high tumor response rate with vem. No new safety signals were detected. Compared to the overall population, pts with an ECOG PS 2 or 3 demonstrated a similar benefit.

Phase 1b/2, open label, multicenter, study of intratumoral SD-101 in combination with pembrolizumab in anti-PD1 naïve & experienced metastatic melanoma patients.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 9550-9550 ◽  
Author(s):  
Abraham C.F. Leung ◽  
Shivaani Kummar ◽  
Sanjiv S. Agarwala ◽  
John J. Nemunaitis ◽  
Rene Gonzalez ◽  
...  
Keyword(s):  
Injection Site ◽  
Metastatic Melanoma ◽  
Stage Iv ◽  
Low Grade ◽  
Open Label ◽  
Ifn Alpha ◽  
Tumor Lesion ◽  
Grade 3 ◽  
The Individual ◽  
Antigen Presenting

9550 Background: SD-101 is a synthetic CpG-ODN agonist of TLR 9 that stimulates dendritic cells to release IFN-alpha and mature into antigen presenting cells to activate T cell anti-tumor responses. Pembro is a PD-1 inhibitor approved for the treatment of metastatic melanoma. This study, MEL-01 (NCT02521870), assesses the safety and preliminary efficacy of SD-101 in combination with pembro in stage IIIC-IV melanoma. Methods: A modified 3+3 design was used for SD-101 dose escalation of 1, 2, 4, and 8 mg injected in a single tumor lesion Q1W x 4 then Q3W x 7 in combination with pembro (200 mg IV Q3W). Tumor responses were assessed per investigator using RECIST v1.1. Results: In phase Ib, 22 pts were enrolled: median age 64 y/o, male 68%, white 82%, Stage IV/IIIc 86%/14%, LDH > 1 ULN 27%, ≥ 3 prior lines therapy 36%, anti-PD-1 naïve (n = 9) and experienced (n = 13). There has been no dose limiting toxicity (DLT) to date. The most common (≥20%) treatment-related AEs (TRAEs) were transient low-grade fatigue, myalgia, headache, chills and injection site reactions. Grade ≥ 3 TRAEs were observed in 59.1% pts (most common: myalgia 13.6% and injection site pain 13.6%). Immune-related AEs occurred in 2 pts. One had a G2 pneumonitis on Day 23 resulting in drug withdrawal and the other G3 hypophysitis (85 days after last treatment). No deaths occurred. Responses were observed at all doses in PD-1 inhibitor naïve pts, both at the injected and non-injected lesions. A response was seen at the 8 mg dose in PD-1 inhibitor experienced pts. With median f/u of 97 days (max 382), the ORR was 66.7% in the PD-1 inhibitor naïve patients with best overall response of CR 22.2% (n = 2), PR 44.4% (n = 4), SD 11.1% (n = 1), PD 11.1% (n = 1), and NE 11.1% (n = 1). In the PD-1 inhibitor experienced pts: PR 7.7% (n = 1) and SD 38.5% (n = 5). Conclusions: The combination of SD-101 and pembro was well tolerated and demonstrates no worsening of the expected toxicities of each of the individual monotherapies. These interim data support enhanced activity of adding SD-101 to pembro in anti-PD-1 naive metastatic melanoma as well as potential activity in anti-PD-1 experienced pts. Additional follow up data through May 15, 2017 will be presented. Clinical trial information: NCT02521870.

Phase 1b/2, open label, multicenter, study of the combination of SD-101 and pembrolizumab in patients with advanced melanoma who are naïve to anti-PD-1 therapy.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 9534-9534 ◽  
Author(s):  
Mohammed M. Milhem ◽  
Georgina V. Long ◽  
Christopher J. Hoimes ◽  
Asim Amin ◽  
Christopher D. Lao ◽  
...  
Keyword(s):  
Disease Stage ◽  
Open Label ◽  
Stage Iiic ◽  
Kaplan Meier ◽  
Unresectable Stage ◽  
Treatment Naïve ◽  
Phase 1B ◽  
Grade 3 ◽  
Post Hoc

9534 Background: SD-101 is a synthetic CpG TLR9 agonist. Pembrolizumab is a PD-1 inhibitor. SYNERGY-001/KEYNOTE-184 assesses the safety and preliminary efficacy of the combination of SD-101 and pembrolizumab in patients naïve to anti-PD-1/L1 therapy with unresectable stage IIIC-IV melanoma. Methods: SD-101 was evaluated as 2 mg/lesion injected into 1 to 4 lesions and 8 mg/lesion in 1 lesion as 4 weekly doses followed by 7 doses Q3W. Pembrolizumab was administered as 200 mg IV Q3W. CT scans were performed every 9 weeks. Responses were assessed per investigator using RECIST v1.1. Responses and post-hoc Kaplan-Meier analyses of PFS in the ITT population were compared for patients who received 2 mg/lesion with 8 mg/lesion. Results: 86 patients (2 mg: N = 45; 8 mg: N = 41) have been enrolled with similar baseline characteristics: median age = 66 years; male = 67%; ECOG stage 0 = 67%; disease stage: IIIC = 21%; IVM1a/b = 50%; IVM1c = 28%; LDH ≤ ULN = 71%; treatment naïve = 73%. Median follow up to date is 8.1 months in 2 mg group and 8.3 months in 8 mg group. SD-101 safety profile comprises flu-like symptoms with most frequent grade ≥3 SD-101-related AEs of headache (7%), fatigue (7%), malaise (5%), myalgia (4%), and chills (4%). Immune-related AEs were reported in 19%. ORR in 2 mg group = 71% (95% CI: 57, 82) (CR: 13%) and in 8 mg group = 49% (95% CI: 33, 65) (CR: 7%) with responses in both injected and non-injected lesions, including visceral. DOR = not reached (NR) in either group. ORR by baseline PD-L1 expression in 62 patients, 53% of whom were PD-L1 positive: 2 mg = 80%/79% (PD-L1 positive/negative); 8 mg = 62%/40% (PD-L1 positive/negative). PFS was higher in 2 mg group with median PFS in 2 mg = NR (95% CI: Not estimable [NE], NE) and in 8 mg = 10.4 months (95% CI: 4.2, NE), HR = 0.45 (95% CI: 0.21, 0.98), p = 0.036. 6 month PFS rate in 2 mg = 81% and in 8 mg = 60%. 6 month OS rate in 2 mg = 98% and in 8 mg = 92%. Conclusions: The TLR9 innate immune stimulant, SD-101, in combination with pembrolizumab has been well-tolerated, and is showing promising high response rates and PFS, regardless of PD-L1 expression, particularly in patients who received 2 mg SD-101. Clinical trial information: NCT02521870.

Exploration of patients with gastric cancer who benefit from apatinib: An updated real-world study.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 161-161 ◽  
Author(s):  
Guo-ping Sun ◽  
Dongliang Li ◽  
Zhongliang Ning ◽  
Yifu He ◽  
Fenglin Zhang ◽  
...  
Keyword(s):  
Real World ◽  
Combined Chemotherapy ◽  
Line Treatment ◽  
Open Label ◽  
Hand Foot Syndrome ◽  
Third Line ◽  
Grade 3 ◽  
Ecog Ps ◽  
Clinical Trial Information

161 Background: A real-world study to observe the efficacy and safety of apatinib treatment in clinical practice, and explored patients (pts) who could benefit from apatinib. Methods: This is an open-label, prospective, observational study, pts (age ≥ 18 yrs) with pathologically or histologically diagnosed GC who were given apatinib treatment met the inclusion criteria. Results: From September 1, 2017 to September 1, 2018. 954 pts were enrolled. 679 pts received palliative treatment were included in the analysis. 499 (73.6%) were males. The age of the pts was (63.1 ± 10.8) yrs. Pts with ECOG PS 0/1 accounted for 78.1%. Pts received first-line treatment, second-line treatment, third-line treatment or above , respectively were 42.2%, 30.5%, 27.3%. 509 (75.1%) pts were treated with apatinib at dose of 500 mg. There were 375 pts available for efficiency evaluation. Among them, 1 achieved CR, 35 achieved PR, 198 had SD, and 57 had PD, resulting in an ORR of 11.9% and a DCR of 77.4%. The mPFS is 4.2 m (95% CI: 3.5-4.8), OS data was still in follow-up. This study showed its efficacy for pts with monotherapy compared with combined chemotherapy (3.3 m vs. 5.0 m, P = 0.003). The mPFS for patients with hypertension were longer than without hypertension (7.1m vs. 3.7m, P = 0.038). And pts also had longer mPFS with good ECOG PS (0-1) compared to those with poor ECOG PS (2-4) (4.7 m vs. 2.9 m, P = 0.003). The incidence of AEs was 402 (88.2%) and the grade 3/4 treatment-related AEs was 14.7%. The most common treatment-related AEs were debilitation (31.2%), hand-foot syndrome (27.5%), hypertension (25.3%), anorexia (11.5%), diarrhea (10.3%), albumin decreased (38.5%), uric acid elevated (31.6%), and total bilirubin increased (29.1%). Conclusions: In the real world, apatinib is confirmed to be effective and safe for GC pts. Factors associated with better prognosis were apatinib combined chemotherapy, ECOG PS 0/1 and occurrence of hypertension. Further analysis is needed to identify pts who benefit from apatinib treatment. Preliminary results of the study were released in ESMO 2018 Congress (683P). Clinical trial information: NCT 03333967.

First-line avelumab + axitinib therapy in patients (pts) with advanced renal cell carcinoma (aRCC): Results from a phase Ib trial.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 4504-4504 ◽  
Author(s):  
Toni K. Choueiri ◽  
James M. G. Larkin ◽  
Mototsugu Oya ◽  
Fiona C. Thistlethwaite ◽  
Marcella Martignoni ◽  
...  
Keyword(s):  
Objective Response ◽  
Clinical Activity ◽  
Vegf Receptor ◽  
Phase Ib ◽  
Treatment Naïve ◽  
Prior Systemic Therapy ◽  
Grade 3 ◽  
Ecog Ps ◽  
Tumor Types

4504 Background: Combining an immune checkpoint inhibitor with a targeted antiangiogenic agent may leverage complementary mechanisms of action for treatment of aRCC. Avelumab is a fully human anti–PD-L1 IgG1 antibody with clinical activity in various tumor types; axitinib, a VEGF receptor inhibitor, is approved for second-line treatment of aRCC. JAVELIN Renal 100 (NCT02493751) is a phase Ib study evaluating safety and clinical activity of avelumab + axitinib in treatment-naïve pts with aRCC; updated results are reported here. Methods: Eligible pts had confirmed clear-cell aRCC, ≥1 measurable lesion, fresh or archival tumor specimen, ECOG PS ≤1, and no prior systemic therapy. Pts received avelumab 10 mg/kg IV Q2W + axitinib 5 mg orally BID until progression, unacceptable toxicity, or withdrawal. Endpoints included safety (NCI CTCAE v4.03) and objective response (RECIST v1.1). Results: As of Dec 30, 2016, 55 pts (median age 60.0 yrs [range 42.0–76.0]; 76.4% male; 34.5% ECOG PS = 1) were enrolled. 54 pts were treated with avelumab for a median of 24.1 wks (range 2.0–62.0); 55 pts were treated with axitinib for a median of 25.3 wks (range 3.0-61.0). 51 pts (92.7%) had an avelumab-related adverse event (AE) with the therapy combination, the most common (≥30% any grade) were fatigue and diarrhea (30.9% each). 10 pts (18.2%) had a max grade 3 and 1 pt (1.8%) had a max grade 4 avelumab-related AE. 52 pts (94.5%) had an axitinib-related AE with the therapy combination; the most common (≥30% any grade) were diarrhea (52.7%), hypertension (45.5%), dysphonia (43.6%), and fatigue (43.6%). 24 pts (43.6%) had a max grade 3 and 5 pts (9.1%) had a max grade 4 axitinib-related AE. 2 deaths occurred in the study during the reporting period: 1 due to progression and 1 related to both treatments (myocarditis). An AE led to discontinuation of avelumab in 5 pts (9.1%) and axitinib in 4 pts (7.3%). Confirmed ORR was 54.5% (95% CI 40.6–68.0) based on 2 CR and 28 PR. Unconfirmed ORR was 60.0% (95% CI 45.9–73.0). Conclusions: The safety profile of the combination of avelumab + axitinib appears manageable and consistent with those agents administered as monotherapy, and early encouraging antitumor activity was observed. Follow-up is ongoing. Clinical trial information: NCT02493751.

Capecitabine (X) compared to X + erlotinib (E) as first-line treatment in patients (pts) with metastatic colorectal cancer (MCRC): Interim efficacy results from a randomized phase II study

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 14560-14560 ◽  
Author(s):  
M. Vincent ◽  
I. Kerr ◽  
B. Dingle ◽  
M. J. MacKenzie ◽  
M. Sanatani
Keyword(s):  
Phase Ii ◽  
Phase Ii Study ◽  
Growth Factor Receptor ◽  
First Line ◽  
Open Label ◽  
Dry Eyes ◽  
Open Label Phase ◽  
Grade 3 ◽  
Ecog Ps

14560 Background: The oral fluoropyrimidine X (Xeloda®) has efficacy, safety and convenience benefits vs. 5-FU/LV in adjuvant / first-line CRC. E (Tarceva®) inhibits epidermal growth factor receptor (EGFR), which predicts poor prognosis. A randomized open-label phase II study was performed to establish activity of X alone vs. X + E (XE) in first-line. Methods: Pts (ECOG PS 0–2 and/or elevated LDH) with MCRC not eligible for immediate surgical metastatectomy and unwilling/unable to undergo combination chemotherapy were randomized to X (1000mg/m2/d bid d1–14 q3w) or XE (X 1000mg/m2/d bid d1–14 q3w + E 150mg/d). A third arm (E alone) was included but dropped after 13 pts, following safety committee review of progressions at first CT scan. Primary endpoint: time to progression (TTP). Results: 59 pts (median age 65y, range 46–84; 44 M, 15 F) have been accrued (X=21; XE=25; E=13). Mean time on study: 3.8 months (range 0.2–12). 9 pts are on active treatment, 21 pts on follow-up and 29 pts have died. Interim efficacy results are available for 50 pts (X n=15; XE n=22, E n=13). There were no significant differences in response rate, median TTP (4.9 vs. 9.2 months) and median overall survival (18.2 vs. 15.1 months) for X vs. XE. Grade 3 adverse events (AEs) with X were diarrhea, nausea, hand-foot syndrome (HFS), angina, dyspnea (all 5%). Corresponding rates of grade 3 AEs with XE were diarrhea (20%), fatigue (16%), stomatitis (12%), HFS (8%), vomiting (8%), dehydration (8%), thrombosis, weight loss, decreased appetite, dry eyes, headache, anxiety, abdominal pain, anorexia, hyponatremia (all 4%). The only grade 4 AEs were skin rash (4%) and subjective weakness (4%) - both XE. Conclusions: Interim results indicate that XE is at least as effective as X alone in first-line MCRC. Recruitment is continuing and further follow-up may help fully determine the potential benefits of adding E to X. [Table: see text] No significant financial relationships to disclose.

ARMOR2: Galeterone in progressive CRPC patients who have failed oral therapy.

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 71-71 ◽  
Author(s):  
Mary-Ellen Taplin ◽  
Robert B. Montgomery ◽  
Keyword(s):  
Study Drug ◽  
Oral Steroid ◽  
Open Label ◽  
Phase 2 Trial ◽  
Treatment Naïve ◽  
Psa Response ◽  
Steroid Analog ◽  
Grade 3 ◽  
Clinical Trial Information

71 Background: Galeterone is a first-in-class multitargeted oral steroid analog; it suppresses prostate cancer by a combination of AR modulation (antagonism and degradation) and CYP17 inhibition. Safety and proof of concept of galeterone in CRPC was assessed in ARMOR1. Galeterone was reformulated by spray dry dispersion technology (SDD) to optimize PK and remove food effect. ARMOR2 (NCT 01709734) is an open label, 2-part phase 2 trial that evaluates safety and efficacy of SDD galeterone in 4 populations of CRPC patients. These results report Part 1. Methods: Objectives of Part 1: confirm dose equivalence of SDD formulation with evaluation of PK, safety and PSA response. Metastatic (M1) and non-metastatic (M0) treatment naïve CRPC pts enrolled to groups of 1,700, 2,550 or 3,400 mg PO daily. An abiraterone refractory (Abi-R) group of 3 patients opened at 2,550mg. Results: 28 were enrolled in part 1. Safety: All groups were safe by IMC assessment. There were 4 grade 3 adverse events. 2 were unrelated to study drug. 2 had transient G3 ALT elevations (did not recur with rechallenge). There was no AME: supplemental steroids were not required. G4 angioedema occurred in a pt receiving lisinopril (known association with angioedema). Efficacy: PSA response was improved compared to ARMOR1 (AACR 2012. Taplin et al abstract: CT-07). At early follow up Abi-R pts showed improvements in PSA with 1 PSA30% response, 2 with stablized PSA (decline in PSA-V from +0.44 to -0.39 ng/day). Conclusions: Galeterone in SDD formulation is tolerated at doses up to 3,400mg daily. SDD galeterone provides improved PSA response and durability vs. prior formulation. There is evidence of activity in abiraterone refractory patients. Clinical trial information: 01709734. [Table: see text]

APACT: phase III, multicenter, international, open-label, randomized trial of adjuvant nab-paclitaxel plus gemcitabine (nab-P/G) vs gemcitabine (G) for surgically resected pancreatic adenocarcinoma.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 4000-4000 ◽  
Author(s):  
Margaret A. Tempero ◽  
Michele Reni ◽  
Hanno Riess ◽  
Uwe Pelzer ◽  
Eileen Mary O'Reilly ◽  
...  
Keyword(s):  
Disease Free Survival ◽  
Disease Recurrence ◽  
Geographic Region ◽  
Phase Iii ◽  
Lymph Node Status ◽  
Open Label ◽  
Significance Level ◽  
Grade 3 ◽  
Ecog Ps

4000 Background: In metastatic pancreatic cancer (PC), nab-P/G demonstrated significantly longer overall survival (OS) vs G. APACT assessed efficacy & safety of nab-P/G vs G in surgically resected PC. Methods: Treatment (tx)-naive patients (pts) with histologically confirmed PC, macroscopic complete resection, ECOG PS 0/1, & CA19-9 < 100 U/mL were eligible. Stratification factors: resection status (R0/R1), lymph node status (LN+/−), & geographic region. Tx was initiated ≤ 12 wks postsurgery. Pts received nab-P 125 mg/m2 + G 1000 mg/m2 or G 1000 mg/m2 on days 1, 8, 15 of six 28-day cycles. Primary endpoint was disease-free survival (DFS) by independent reviewer (IR); IRs received baseline clinical data & scans. Secondary endpoints were OS & safety. ≈438 DFS events were needed for 90% power to detect an HR for disease recurrence or death of 0.73 with nab-P/G vs G at a 2-sided significance level of 0.05. Results: 866 pts were randomized. Median age was 64 y (range, 34 - 86); most pts had ECOG PS 0 (60%), LN+ (72%), & R0 (76%). 69% of pts completed 6 tx cycles ( nab-P/G, 66%; G, 71%). Median follow up for OS was 38.5 mo. Median IR-assessed DFS (439 events) was 19.4 mo ( nab-P/G) vs 18.8 mo (G) (HR, 0.88; 95% CI, 0.729 - 1.063; stratified log-rank P = 0.1824). Investigator-assessed DFS (571 events) was 16.6 mo ( nab-P/G) vs 13.7 mo (G) (HR, 0.82; 95% CI, 0.694 - 0.965; nominal P = 0.0168). Interim OS (427 events) was 40.5 mo ( nab-P/G) vs 36.2 mo (G) (HR, 0.82; 95% CI, 0.680 - 0.996; nominal P = 0.045). Grade ≥ 3 TEAEs were reported in 86% vs 68% of pts with nab-P/G vs G. The most common grade ≥ 3 hematologic & nonhematologic TEAEs with nab-P/G vs G were neutropenia (49% vs 43%) & fatigue (10% vs 3%). TEAEs led to death in 2 pts in each arm. Conclusions: IR DFS with nab-P/G was not significantly longer vs G; median DFS with G was longer than historical data. DFS by investigator (sensitivity analysis) and interim OS were improved with nab-P/G vs G (HR 0.82 for both). Adjuvant nab-P/G may be an option for pts who are ineligible for FOLFIRINOX. Additional OS follow-up may better support nab-P/G as an option in the adjuvant setting. Clinical trial information: NCT01964430.

A phase II, randomized trial (CONCERT-1) of chemoradiotherapy (CRT) with or without panitumumab (pmab) in patients (pts) with unresected, locally advanced squamous cell carcinoma of the head and neck (LASCCHN).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 5502-5502 ◽  
Author(s):  
Jordi Giralt ◽  
Andre Fortin ◽  
Ricard Mesia ◽  
Heikki Minn ◽  
Michael Henke ◽  
...  
Keyword(s):  
Human Monoclonal Antibody ◽  
Locally Advanced ◽  
Growth Factor Receptor ◽  
Mucosal Inflammation ◽  
Open Label ◽  
Hpv Status ◽  
Biomarker Analysis ◽  
Grade 3 ◽  
Fatal Adverse Events ◽  
Ecog Ps

5502 Background: Pmab is a fully human monoclonal antibody against the epidermal growth factor receptor. We evaluated the safety and efficacy in pts receiving CRT alone or CRT plus pmab (PCRT) as 1st‑line treatment of LASCCHN (sponsored and funded by Amgen Inc.). Methods: Pts with stage III, IVA, or IVB previously untreated LASCCHN of all sites excluding the nasopharynx were randomized 2:3 to open-label CRT or PCRT. CRT included cisplatin 100 mg/m2 for 3 cycles during standard fractionation radiotherapy (RT). PCRT included pmab 9.0 mg/kg + cisplatin 75 mg/m2, both administered with RT as in the CRT arm. The primary endpoint was local regional control (LRC) rate at 2 years; key secondary endpoints included PFS, OS, and safety. Preplanned HPV subset analysis, as determined by p16 immunohistochemistry, was performed on available samples. Results: Of 150 treated pts (87 pts PCRT, 63 pts CRT), 87% were men; median (range) age was 57 (39-77) years; ECOG PS 0: 68%. Of 99 pts with tumor evaluable for HPV, 42% were HPV+. Overall, the 2-year LRC rate (95% CI) was 61% (50%-71%) for PCRT and 68% (54%-78%) for CRT. PFS events occurred in 40% of the PCRT and 35% of CRT arm (HR [95% CI] 1.15 [0.68-1.96]; p=0.61). Death occurred in 36% of the PCRT arm vs 24% of the CRT arm (HR [95% Cl] for OS 1.63 [0.88-3.02]; p=0.12). Disease progression was the cause of death in 22% of PCRT pts and 10% of CRT pts. There were no differences in outcome by tumor HPV status. No difference in fatal adverse events (AEs) was seen between arms. Grade 3+ AEs occurred in 85% vs 68% of pts (PCRT vs CRT). Differences in grade 3+ toxicity between treatment arms (PCRT, CRT) were most pronounced for mucosal inflammation (55%, 24%), radiation skin injury (28%, 13%), dysphagia (40%, 27%), and rash (11%, 0%). RT delays of >10 days occurred in 16% of the PCRT arm and 3% of the CRT arm. Median cisplatin cumulative dose received was 223.1 mg/m2 in the PCRT arm and 296.9 mg/m2 in the CRT arm, reflective of differences in planned dose. Conclusions: The addition of pmab to CRT did not show an increase in efficacy and was associated with increased toxicity. Further results of HPV biomarker analysis will be presented.

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