A phase IB study of ipilimumab with peginterferon alfa-2b in patients with unresectable melanoma.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 9079-9079 ◽  
Author(s):  
Ragini Reiney Kudchadkar ◽  
Geoffrey Thomas Gibney ◽  
Jeffrey Weber ◽  
Ann Chen ◽  
Kim Smith ◽  
...  
Keyword(s):  
Small Population ◽  
Anticardiolipin Antibodies ◽  
Double Stranded Dna ◽  
Patient Decision ◽  
Grade 3 ◽  
Peginterferon Alfa ◽  
Male Subjects ◽  
Dose Reductions ◽  
Unacceptable Toxicity ◽  
Clinical Trial Information

9079 Background: Peginterferon alfa-2b (Sylatron) as adjuvant therapy has been shown to benefit patients with high-risk resected melanoma and some interferon studies have shown that the induction of autoantibodies may correlate with benefit. Ipilimumab (IPI, Yervoy) is a fully human anti-CTLA-4 antibody that induces autoimmune toxicity that in some cases appears to correlate with clinical benefit. This study was performed to assess whether ipilimumab can be safely administered with peginterferon alfa-2b. Methods: This study combined IPI at 3mg/kg every 3 weeks for 4 doses along with concurrent peginterferon alfa-2b at 3 mcg/kg weekly for up to 156 weeks or until disease progression, unacceptable toxicity or patient decision to discontinue. The study was designed to obtain toxicity, tolerability and autoimmune antibody data and to define a well-tolerated dose of the combination. Results: Median age was 61 with 9 female and 8 male subjects. There were 3 patients (pts) with partial responses, 1 stable disease, and 6 with progressive disease in 10 pts evaluable for response thus far. Six pts have not yet completed cycle 1 and therefore are not evaluable for response at the time of this publication but will be presented. One pt withdrew consent prior to finishing cycle 1. Toxicities from peginterferon alfa-2b 3mcg/kg were dose-limiting with 7 pts requiring dose reduction in peginterferon alfa-2b secondary to toxicity. The Grade 3 events leading to dose reductions were nausea and vomiting, leucopenia, dehydration, and hyponatremia. peginterferon alfa-2b was dose reduced to 2 mcg/kg weekly in future pts after these toxicities were noted. No Grade 3 or 4 toxicities attributable to ipilimumab have occurred thus far. No Grade 3 or 4 events have been noted to date in the10 pts initiated at 2 mcg/kg of peginterferon alfa-2b. There was no significant change in the presence autoantibodies (ANA, anti-double stranded DNA, antithyroglobulin, antimicrosomal antibodies, and anticardiolipin antibodies) between responders and non-responders in the evaluable pts. Conclusions: Peginterferon alfa-2b added to IPI results in an excellent response rate in this small population. Peginterferon alpha-2b at 2 mcg/kg weekly with IPI at 3 mg/kg every 3 weeks appears well-tolerated and the combination warrants further exploration. Clinical trial information: NCT01496807.

Feasibility of an adapted schedule of carboplatin plus paclitaxel in elderly women with advanced ovarian cancer: A retrospective cohort.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 5546-5546
Author(s):  
Benjamin Nicaise ◽  
Soraya Mebarki ◽  
Mathilde Gisselbrecht ◽  
Elisabeth Ashton ◽  
Henri Azais ◽  
...  
Keyword(s):  
Elderly Patients ◽  
Progressive Disease ◽  
Elderly Women ◽  
Advanced Ovarian Cancer ◽  
Early Discontinuation ◽  
Grade 3 ◽  
Vulnerable Elderly ◽  
Dose Delay ◽  
Dose Reductions ◽  
Unacceptable Toxicity

5546 Background: The EWOC-1 trial compared Carboplatin monotherapy (C mono) to two different Carboplatin + Paclitaxel (CP) regimens (weekly or 3-weekly) in vulnerable elderly patients treated for advanced ovarian cancers (OC). This study was closed prematurely because of a worse outcome in the C mono group. Both CP regimens were equivalent in terms of feasibility and efficacy with different toxicity profiles. Optimal CP regimen in elderly patient is still unknown. Here we propose a study of another adapted regimen of CP (aCP) performed in elderly patients in our institution. Methods: We retrospectively analyzed OC patients ≥ 70 years who received a Carboplatin AUC 4-5 d1q3week + Paclitaxel 80 mg/m² d1-d8 q3week regimen between 2015 and 2019. Primary endpoint was treatment feasibility according to the EWOC-1 standard: completion of 6 courses of chemotherapy without early stopping for disease progression, death or unacceptable toxicity (adverse event (AE) related to chemotherapy or treatment procedure leading either to early treatment stopping, to an unplanned hospital admission or to death or to a dose delay lasting more than 14 days or more than 2 dose reductions). Results: We identified 36 pts with a median age of 79 years (table). All patient but one had an ONCODAGE-G8 score ≤ 14, 30.6% of patients had a comorbidity Charlson’s index > 4 and 52.5% had an albumin rate < 35 g/L. The feasibility endpoint was met in 58.3% of patients (IC95% = [25.6; 57.8]). Main causes of treatment failure (TF) were early discontinuation because of toxicity in 6 patients (16.7%) and progressive disease in 3 patients (8.33%). Median PFS was 35.3 months (IC95% = [22.7; NR]) and median OS was 62.1 months (IC95% = [31.4.0; NR]). The most frequent AE were asthenia (all grades = 94.4%, grade 3-4 = 13.9%), anemia (all grades = 94.4%, grade 3-4 = 27.8%), neutropenia (all grades = 66.7%, grade 3-4 = 38.9%) and neuropathy sensory (all grades = 61.1%, no grade 3-4). Non high-grade-serous histological type and a poor Charlson’s score were associated with a higher rate of TF (100% and 63.6%, respectively). Conclusions: These results are consistent with the findings of the EWOC-1 trial in both CP regimens and suggest that aCP could be non-inferior with an acceptable toxicity profile. Further prospective and comparative studies are mandatory to confirm this trend and to better identify predictive factors of TF in OC elderly patients.[Table: see text]

Updated results from a randomized phase II dose-ranging study of the JAK2-selective inhibitor SAR302503 in patients with myelofibrosis (MF).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 7109-7109 ◽  
Author(s):  
Animesh Dev Pardanani ◽  
Catriona H. M. Jamieson ◽  
Nashat Y. Gabrail ◽  
Claudia Lebedinsky ◽  
Guozhi Gao ◽  
...  
Keyword(s):  
High Risk ◽  
Phase Ii ◽  
Median Number ◽  
Randomized Phase Ii ◽  
Night Sweats ◽  
Dose Ranging ◽  
Grade 3 ◽  
Number Of Cycles ◽  
Dose Reductions ◽  
Unacceptable Toxicity

7109 Background: We previously reported results of treating MF patients with 3 cycles of 300, 400, or 500 mg of SAR302503 (NCT01420770; Blood 2012;120:21 Abs 2837). This is a report of efficacy and safety after 6 cycles. Methods: Patients ≥18 years of age with intermediate-2 or high-risk MF and splenomegaly were eligible. SAR302503 is administered orally, once a day in consecutive 4-week cycles until disease progression or unacceptable toxicity. Spleen response (≥35% reduction in spleen volume vs baseline) was assessed by MRI/CT (blinded independent central review). Results: 31 patients were enrolled (n=10 in the 300 and 400 mg groups; n=11 to 500 mg). Risk status was balanced in all but the 300 mg group (70% high-risk). Most patients were JAK2V617F positive (90%) and blood transfusion independent (81%). Spleen response rates at the end of cycle (EOC) 6 (secondary end point) were 30% (3/10) in the 300 mg group, 60% (6/10) with 400 mg, and 55% (6/11) with 500 mg compared with EOC 3 rates of 30%, 50%, and 64%, respectively. One patient on 500 mg who had a spleen response at EOC 3 (39% reduction), but not at EOC 6 (25% reduction) had dose reductions to 200 mg due to anemia. Median number of cycles was 13 (range, 2–17) and 24 patients have been on treatment >12 months. SAR302503 reduced baseline constitutional symptoms at the EOC 3, with the greatest responses for night sweats in 14/15 patients (93%), itching 10/14 (71%), early satiety and abdominal pain, each in 10/18 (56%). Most common adverse events were anemia and diarrhea, with grade 3–4 rates of 58% and 13%, respectively. The rate of grade 3–4 thrombocytopenia was 16%. There was no grade 3–4 neutropenia. The diarrhea rate tended to decrease after the first 2 treatment cycles. There have been no reports of withdrawal syndrome after stopping SAR302503. Median JAK2V617F allele burden was 93% at baseline, 87% at the EOC 3, and 78% at EOC 6 in 19/26 patients who had available samples. The expression of 22 of 97 cytokines was significantly regulated (≥1.5 fold difference; p<0.05) after cycle 1. Conclusions: In this Phase II trial, continued treatment with SAR302503 was associated with clinically meaningful reductions in splenomegaly. Symptom data will be updated. Clinical trial information: NCT01420770.

A dose-escalation phase I study of a first-in-class cancer stemness inhibitor in patients with advanced malignancies.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 2542-2542 ◽  
Author(s):  
Adrian Langleben ◽  
Jeffrey G. Supko ◽  
Sebastien J. Hotte ◽  
Gerald Batist ◽  
Hal W. Hirte ◽  
...  
Keyword(s):  
Dose Escalation ◽  
Phase 1 ◽  
Cancer Stemness ◽  
Advanced Malignancies ◽  
Progression Of Disease ◽  
Excellent Safety Profile ◽  
Grade 3 ◽  
Anti Tumor Activity ◽  
Unacceptable Toxicity ◽  
Clinical Trial Information

2542 Background: Cancer Stem Cells (CSC) are considered to be fundamentally responsible for malignant growth, relapse, metastasis, and resistance to conventional therapies. BBI608 is an orally-administered first-in-class cancer stemness inhibitor which blocks CSC self-renewal and induces cell death in CSC as well as non-stem cancer cells by inhibition of the Stat3, Nanog and b-catenin pathways, and has shown potent anti-tumor and anti-metastatic activities pre-clinically. Methods: A phase 1 dose escalation studyin adult patients with advanced cancer who had failed standard therapies was conducted to determine the safety, tolerability, recommended phase 2 dose (RP2D), pharmacokinetics and preliminary anti-tumor activity of BBI608. A modified Simon accelerated titration scheme was used for dose escalation, with a cycle consisting of twice-daily oral administration of BBI608 for 4 weeks. Cycles were repeated every 4 weeks (28 days) until progression of disease, unacceptable toxicity, or other discontinuation criteria were met. Results: Fourteen cohorts (N=41) were dosed from 20 mg to 2000 mg/day with adverse events being generally mild; the most common being grade 1-2 diarrhea, nausea, anorexia and fatigue. Four grade 3 events included diarrhea (n=3) and fatigue (n=1). MTD was not reached and further dose escalation was limited by pill burden. By the 400 mg/day dose level the plasma concentration of BBI608 was sustained for over 8 hours at a concentration above 1.5 uM (several fold above the IC50). 17/26 patients evaluable for tumor response achieved SD, for a DCR of 65%. Prolonged TTP was observed in 12/26 evaluable patients (46%), including patients with colorectal (CRC), head and neck, gastric, ovarian, melanoma, and breast cancer. In the subset of patients with CRC (N=18), SD was seen in 8/12 evaluable (67%). A median PFS of 14 weeks and median OS of 47 weeks were observed in evaluable CRC patients. Conclusions: Dose escalation of BBI608, a first-in-class cancer stem cell pathway inhibitor, has been achieved without dose limiting toxicity. BBI608 has shown an excellent safety profile, favorable pharmacokinetics, and encouraging signs of clinical activity particularly in CRC Clinical trial information: NCT01775423.

First-line (1L) avelumab treatment in patients (pts) with metastatic Merkel cell carcinoma (mMCC): Preliminary data from an ongoing study.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 9530-9530 ◽  
Author(s):  
Sandra P. D'Angelo ◽  
Jeffrey Russell ◽  
Jessica Cecile Hassel ◽  
Celeste Lebbe ◽  
Bartosz Chmielowski ◽  
...  
Keyword(s):  
Safety Profile ◽  
Response Rate ◽  
Objective Response ◽  
Durable Response ◽  
Phase 2 Study ◽  
Grade 3 ◽  
Related Reaction ◽  
Unacceptable Toxicity ◽  
Clinical Trial Information

9530 Background: MCC is a rare, aggressive skin cancer. Avelumab is a fully human anti–PD-L1 antibody. In a phase 2 study in pts with distant mMCC who progressed after prior chemotherapy (JAVELIN Merkel 200; NCT02155647), avelumab showed a manageable safety profile and durable responses, including an objective response rate (ORR) of 31.8%, estimated 6-month durable response rate of 29%, and 6-month overall survival rate of 69%. Here, we report preliminary results from a separate cohort of pts with chemotherapy-naïve mMCC enrolled in the same study. Methods: Eligible pts with mMCC and no prior systemic treatment for metastatic disease received avelumab 10 mg/kg Q2W until confirmed progression, unacceptable toxicity, or withdrawal. Tumors were assessed every 6 weeks (RECIST v1.1). Adverse events (AEs) were assessed by NCI CTCAE v4.0. Results: As of Dec 30, 2016, 29/112 planned pts had been enrolled. Median age was 75.0 years (range 47–87). Median treatment duration was 8.1 weeks (range 2.0–37.9). Of 16 pts with ≥3 months of follow-up, unconfirmed ORR was 68.8% (95% CI 41.3–89.0) with CR in 18.8%; confirmed ORR was 56.3% (95% CI 29.9–80.2; 1 unconfirmed PR with discontinuation). Of 25 pts with ≥6 weeks of follow-up, unconfirmed ORR was 64.0% (95% CI 42.5–82.0). All responses were ongoing at last follow-up, including in 5/5 pts with ≥6 months of follow-up (potential to confirm responses). 20/29 pts (69.0%) had a treatment-related AE (TRAE), including grade 3–4 TRAE in 5 pts (17.2%). TRAEs led to discontinuation in 5 pts (17.2%): 2 pts with infusion-related reaction, and 1 pt each with elevated AST and ALT, cholangitis, and paraneoplastic syndrome. There were no treatment-related deaths. 21/29 pts (72.4%) remain on treatment. Conclusions: In initial results from a cohort of chemotherapy-naïve pts with mMCC, avelumab was associated with early responses and a manageable safety profile, consistent with findings for second-line or later avelumab treatment in a previous cohort. These results suggest that responses mature to become durable and the use of 1L avelumab may increase the probability of response vs later-line treatment. Enrollment and follow-up in this 1L cohort are ongoing. Clinical trial information: NCT02155647.

Phase II study of antidisialoganglioside antibody, dinutuximab, in combination with GM-CSF in patients with recurrent osteosarcoma (AOST1421): A report from the Children’s Oncology Group.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 10508-10508
Author(s):  
Pooja Hingorani ◽  
Mark D. Krailo ◽  
Allen Buxton ◽  
Paul R. Hutson ◽  
Justin Davis ◽  
...  
Keyword(s):  
Progressive Disease ◽  
Adolescent And Young Adult ◽  
Sufficient Evidence ◽  
Gm Csf ◽  
Phase 2 Study ◽  
Accrual Rate ◽  
Resected Tumor ◽  
Grade 3 ◽  
Unacceptable Toxicity ◽  
Clinical Trial Information

10508 Background: Treatment of patients with recurrent osteosarcoma (OS) is challenging and novel effective therapies are urgently needed. This study evaluated disease control rate (DCR) in patients with recurrent pulmonary OS, when treated with dinutuximab plus cytokine therapy as compared to a historical benchmark. The rationale for dinutuximab was the ubiquitous ( > 95%) GD2 positivity in OS tumors and cell lines. Methods: AOST1421 was a single-arm phase 2 study. Patients with recurrent pulmonary OS in complete surgical remission were eligible. Patients received five cycles of dinutuximab 70mg/m2/cycle with GM-CSF. Two different dinutuximab infusion schedules were used - 35mg/m2/day over 20 hours (2-day) and 17.5mg/m2/day over 10 hours (4-day) schedule. Primary end point was DCR, defined as proportion of patients event-free at 12 months from enrollment. Events were progressive disease or death within 12 months attributed to treatment or progression. The historical benchmark was AOST0221 with a 12-month DCR of 20% (95% CI 10-34%). Success was defined as ≥16/ 39 patients ( > 40%) event-free at 12 months from enrollment. Secondary objectives included toxicity evaluation and dinutuximab pharmacokinetics (PK). Results: Forty-one patients were enrolled from Nov 2015 - Jan 2018. Thirty nine were eligible and evaluable (age 7-26 yr; median 15 yr). Data current to December 31, 2019 was used for analysis. Accrual rate was higher than expected (22.1 vs. 19.2 patients/ yr.) despite a concurrently open competing study. One of 136 administered therapy cycles met criteria for unacceptable toxicity when one patient receiving the 2-day schedule died after cycle 2 due to an unknown cause, attributed as probably related to protocol therapy. The protocol was revised to allow only the 4-day schedule. Other ≥ Grade 3 toxicities occurring in > 10 % participants were expected dinutuximab toxicities such as pain, diarrhea, hypoxia and hypotension. Dinutuximab did not demonstrate sufficient evidence of efficacy as 27/ 39 patients experienced an event for a DCR of 30.7% (95% CI 17- 47%). PK studies are pending and will be reported. Conclusions: Dinutuximab toxicity in adolescent and young adult OS patients was similar to younger patients. While GD2 remains a relevant target in OS, combination of dinutuximab with GM-CSF did not meet the targeted successful DCR in patients with completely resected tumor. Other strategies for targeting GD2 or dinituximab combination therapy may still be warranted. Clinical trial information: NCT02484443.

Phase II study of ibrutinib in advanced carcinoid and pancreatic neuroendocrine tumors.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 434-434
Author(s):  
Taymeyah E. Al-Toubah ◽  
Tiffany Valone ◽  
Michael J. Schell ◽  
Jonathan R. Strosberg
Keyword(s):  
Neuroendocrine Tumors ◽  
Phase Ii ◽  
Objective Response ◽  
Prior Therapy ◽  
Progression Of Disease ◽  
Prospective Phase ◽  
Well Differentiated ◽  
Grade 3 ◽  
Unacceptable Toxicity ◽  
Clinical Trial Information

434 Background: Ibrutinib is an orally administered, inhibitor of Bruton’s tyrosine kinase (Btk). Preclinical data suggest that mast cells are recruited with neuroendocrine tumors (NETs) where they remodel the stroma and stimulate angiogenesis, driving macroscopic tumor expansion. Ibrutinib inhibits mast cell degranulation, and has been associated with regression of a mouse insulinoma model. Methods: A prospective, phase II trial evaluated patients with advanced GI/lung NETs and pNETs who had evidence of progression within 12 months of study entry on at least one prior therapy. Patients received ibrutinib 560mg daily until unacceptable toxicity, progression of disease, or withdrawal of consent. Primary endpoint was objective response rate. Results: 20 patients were enrolled on protocol from November 2015 – December 2017 (15 carcinoid and five pNETs). No patients experienced objective response. Median PFS was 3.1 months. A total of 43 drug related AEs were captured as probably or definitely associated with ibrutinib. Five patients experienced probably or definitely related grade 3 AEs and one patient experienced a probably related grade 4 AE. Five patients discontinued treatment prior to radiographic assessment. Conclusions: Ibrutinib does not show significant evidence of activity when compared to other agents (e.g. Everolimus) in well-differentiated gastroenteropancreatic and lung NETs. Clinical trial information: 02575300.

Immune checkpoint inhibition (ICI) in combination with SBRT in patients with advanced pancreatic adenocarcinoma (aPDAC).

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 192-192 ◽  
Author(s):  
Gagandeep Brar ◽  
Changqing Xie ◽  
Charalampos S. Floudas ◽  
M. Pia Morelli ◽  
Suzanne Fioravanti ◽  
...  
Keyword(s):  
Partial Response ◽  
Locally Advanced ◽  
Primary Objective ◽  
Clinical Activity ◽  
Correlative Analysis ◽  
Progression Of Disease ◽  
New Treatment ◽  
Grade 3 ◽  
Unacceptable Toxicity ◽  
Clinical Trial Information

192 Background: Chemotherapy in aPDAC has resulted in only modest improvements in outcome. The effectiveness of ICI monotherapy is also limited in PDAC, suggesting an immunogenic inert tumor microenvironment. SBRT is safe and effective in locally advanced PDAC and exhibits enhanced antitumor immunity. We hypothesize that ICI plus SBRT will improves immunomodulatory effects of ICI in patients with aPDAC resulting in a greater clinical benefit. Methods: Eligible patients with aPDAC were enrolled to four different treatment cohorts. Cohort 1: Durvalumab (Durva) 1500 mg every 4 weeks + SBRT 1 fraction x 8Gy on day 1. Cohort 2: SBRT 5 fractions x 5Gy followed by Durva. Cohort 3: Durva + Tremelimumab (Treme) 75 mg every 4 weeks + SBRT 1 fraction x 8Gy on day 1. Cohort 4: SBRT 5 fractions x 5Gy followed by Durva + Treme. This was continued until unacceptable toxicity or progression of disease. A biopsy was performed at baseline and pre-cycle 2 of treatment for exploratory correlative analysis. The primary objective was to evaluate the safety and feasibility of combining ICI and SBRT to enhance the efficacy of ICI. Results: 51 patients with aPDAC were enrolled and 31 patients were evaluable for the efficacy. The most commonly TRAEs were lymphopenia. Grade 3-4 AEs were lymphopenia and anemia. No dose limiting toxicities were seen. Out of total 31 evaluable patients, 1 patient achieved a confirmed partial response seen in Cohort 1 and 2 patients in Cohort 4, and 7 stable disease across the 4 treatment arms. Median PFS and OS was 1.7 months (95% CI 0.7-2.8 months) and 3.4 months (95% CI 0.9-11.4 months) in cohort 1; 2.6 months (95% CI 2.1-4.7 months) and 9.1 months (95% CI 3.4-18.7 months)in cohort 2; 1.6 months (95% CI 0.5-4.0 months) and 3.0 months (95% CI 0.7-6.6 months) in cohort 3; and 3.2 months (95% CI 1.5-16.5months) and 6.4 months (95% CI 1.5-17.6 months) in cohort 4. Conclusions: The combination of ICI and SBRT is safe and well tolerated in patients with aPDAC. The overall response rate of 9.6% including 2 patients who achieved a durable partial response lasting over 12 months, suggests meaningful clinical activity. This signifies that ICI and SBRT is a potential new treatment for aPDAC. Clinical trial information: NCT02311361.

Efficacy and safety in older patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) receiving cabazitaxel (CBZ) versus abiraterone (ABI) or enzalutamide (ENZ) in the CARD study.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 5559-5559 ◽  
Author(s):  
Cora N. Sternberg ◽  
Daniel Castellano ◽  
Johann S. De Bono ◽  
Karim Fizazi ◽  
Bertrand F. Tombal ◽  
...  
Keyword(s):  
Disease Progression ◽  
Efficacy And Safety ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Previously Treated ◽  
Grade 3 ◽  
Post Hoc ◽  
The Impact ◽  
Unacceptable Toxicity ◽  
Clinical Trial Information

5559 Background: In the CARD (NCT02485691) study, radiographic PFS (rPFS), PFS and OS were significantly improved with CBZ vs. androgen-signaling-targeted agents (ARTA; ABI or ENZ) in pts with mCRPC who had received docetaxel (DOC) and progressed within 12 months (mo) on an alternative ARTA. This analysis evaluated the impact of age (< 70 vs. ≥ 70 years) on the efficacy and safety of CBZ and ARTAs in CARD. Methods: 255 pts with mCRPC were randomized 1:1 to CBZ (25 mg/m2 IV Q3W + prednisone [P] + G-CSF) vs. ABI (1000 mg PO + P) or ENZ (160 mg PO) until disease progression, unacceptable toxicity or pt request. Pts were eligible if they had received ≥ 3 cycles of DOC and progressed ≤ 12 mo on the previous alternative ARTA. Primary endpoint was rPFS. Subgroup analysis of older (≥ 70 years; n = 135) and younger (< 70 years; n = 120) pts was pre-specified for rPFS; others were post hoc. Results: rPFS was significantly improved vs. ARTA in both older (median 8.2 vs. 4.5 mo; HR 0.58; 95% CI 0.38–0.89) and younger pts (median 7.4 vs. 3.2 mo; HR 0.47; 95% CI 0.30–0.74). Median OS for CBZ vs. ARTA was 13.9 vs. 9.4 mo (HR 0.66; 95% CI 0.41–1.06) in older pts and 13.6 vs. 11.8 mo (HR 0.66; 95% CI 0.41–1.08) in younger pts. PFS, tumor, PSA and pain responses also favored CBZ, regardless of age. Grade ≥ 3 adverse events (AEs) occurred in 57.8% vs. 49.3% of older pts receiving CBZ vs. ARTA and 48.4% vs. 42.1% in younger pts. AEs leading to death were more frequent with ARTA, mainly due to disease progression. Conclusions: CBZ had improved efficacy outcomes vs. ARTA in pts with mCRPC previously treated with DOC and the alternative ARTA, regardless of age. Grade ≥ 3 cardiac AEs were more frequent in older pts treated with ARTA. A higher rate of AEs was reported in older vs. younger pts, for ARTA and CBZ. CBZ and ARTA had different safety profiles in older compared with younger pts. Clinical trial information: NCT02485691 . Funding: Sanofi. [Table: see text]

Adverse events (AEs) with maintenance olaparib tablets in patients (pts) with BRCA-mutated (BRCAm) platinum-sensitive relapsed serous ovarian cancer (PSR SOC): Phase III SOLO2 trial.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 5518-5518 ◽  
Author(s):  
Jonathan A. Ledermann ◽  
Alain Lortholary ◽  
Richard T. Penson ◽  
Emma Gibbs ◽  
Diane M. Provencher ◽  
...  
Keyword(s):  
Parp Inhibitor ◽  
Phase Iii ◽  
Low Grade ◽  
Platinum Sensitive ◽  
Treatment Dose ◽  
Common Grade ◽  
Grade 3 ◽  
Platinum Chemotherapy ◽  
Dose Reductions ◽  
Clinical Trial Information

5518 Background: In the SOLO2 trial (ENGOT Ov-21; NCT01874353), maintenance therapy with the PARP inhibitor olaparib significantly improved PFS vs placebo (PBO) in BRCAm PSR SOC pts (HR 0.30, 95% CI 0.22–0.41, P<0.0001; median 19.1 vs 5.5 months) and was well tolerated (Pujade-Lauraine et al, SGO 2017). We analyzed AEs in SOLO2, the first study in PSR SOC to use the olaparib tablet formulation. Methods: Pts with BRCAm PSR SOC, who were in response to platinum chemotherapy, were treated with olaparib (300 mg bid; tablets; n=195) or PBO (n=99) until progression. AEs were graded by CTCAE v4.0. Results: The most common AEs with olaparib – nausea, fatigue/asthenia, anemia, and vomiting – were largely grade 1–2, though anemia was the most common grade ≥3 AE. AEs of fatigue/asthenia, vomiting and nausea generally improved as treatment continued, though fatigue/asthenia and anemia could last for several months (table). Most AEs were manageable by supportive treatment, dose interruptions (olaparib, 45%; PBO, 18%) and dose reductions (olaparib, 25%; PBO, 3%). Discontinuation of olaparib due to AEs was minimal (11%); anemia and neutropenia were the only AEs leading to discontinuation of olaparib in >one pt. Conclusions: Most AEs experienced by pts receiving olaparib tablets in SOLO2 were low grade and manageable. Initial nausea, vomiting and fatigue generally improved with ongoing treatment. The majority of AEs first occurred within the first three months of treatment. AEs causing treatment discontinuation were rare and mainly hematological. Clinical trial information: NCT01874353. [Table: see text]

Safety, clinical activity, and PD-L1 expression of avelumab (MSB0010718C), an anti-PD-L1 antibody, in patients with metastatic urothelial carcinoma from the JAVELIN Solid Tumor phase Ib trial.

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 367-367 ◽  
Author(s):  
Andrea B. Apolo ◽  
Jeffrey R. Infante ◽  
Omid Hamid ◽  
Manish R. Patel ◽  
Ding Wang ◽  
...  
Keyword(s):  
Urothelial Carcinoma ◽  
Performance Status ◽  
Progression Free Survival ◽  
Clinical Activity ◽  
Ecog Performance Status ◽  
Free Survival ◽  
Metastatic Urothelial Carcinoma ◽  
Grade 3 ◽  
Unacceptable Toxicity ◽  
Clinical Trial Information

367 Background: Avelumab* (MSB0010718C) is a fully human anti-PD-L1 IgG1 antibody being investigated in multiple clinical trials. We report safety and clinical activity of avelumab as a second-line therapy in patients (pts) with metastatic urothelial carcinoma (mUC) based on level of PD-L1 expression (NCT01772004). Methods: Pts with mUC unselected for PD-L1 expression received avelumab at 10 mg/kg Q2W by IV infusion until confirmed progression, unacceptable toxicity, or any criterion for withdrawal occurred. Tumors were assessed every 6 wks (RECIST 1.1). Best overall response rate (ORR) and progression-free survival (PFS) were evaluated. Adverse events (AEs) were graded by NCI-CTCAE v4.0. PD-L1 expression was assessed by immunohistochemistry. Results: As of 19 Mar 2015, 44 pts (30 men, 14 women) with mUC were treated with avelumab (median 13 wks [range 2-28]) and followed for a median of 3.5 mo (range 3.0-5.0). Median age was 68y (range 30-84), ECOG performance status was 0 (43.2%) or 1 (56.8%), and pts had received a median of 2 prior therapies (range 1- ≥ 4). Treatment-related treatment-emergent AEs (TR-TEAEs) of any grade occurred in 26 pts (59.1%); those occurring ≥ 10% were grade 1/2 infusion-related reactions (8 [18.2%]) and fatigue (7 [15.9%]). One pt had grade 3 asthenia. There were no treatment-related deaths. ORR was 15.9% (7 pts; 95% CI: 6.6, 30.1) with 1 CR and 6 PRs; 6 responses were ongoing at data cutoff. Stable disease (SD) was observed in 19 pts (42.3%) and disease-control rate (CR+PR+SD) was 59.1%. PD-L1 expression was evaluable in 32 pts. Using a ≥ 5% cutoff (10/32 [31.3%] were PD-L1+), ORR was 40.0% in PD-L1+ pts (4/10) vs 9.1% in PD-L1– pts (2/22; p= 0.060). PFS rate at 12 wks was 70.0% (95% CI: 32.9, 89.2) in PD-L1+ pts vs 45.5% (95% CI 22.7, 65.8) in PD-L1− pts. Conclusions: Avelumabshowed an acceptable safety profile and had clinical activity in pts with mUC. There was a trend towards higher ORR and prolonged PFS rate at 12 wks in pts with PD-L1+ mUC. Further analyses of PD-L1 expression and clinical activity of avelumab in UC are ongoing. *Proposed INN. Clinical trial information: NCT01772004.

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