A single-arm, phase II study assessing the efficacy of pembrolizumab (pembro) plus radiotherapy (RT) in metastatic triple negative breast cancer (mTNBC).

2018 ◽  
Vol 36 (5_suppl) ◽  
pp. 14-14 ◽  
Author(s):  
Heather L. McArthur ◽  
Christopher Andrew Barker ◽  
Ayca Gucalp ◽  
Lizza Lebron-Zapata ◽  
Yong Hannah Wen ◽  
...  
Keyword(s):  
Disease Progression ◽  
Phase Ii ◽  
Metastatic Disease ◽  
Stable Disease ◽  
Phase Ii Study ◽  
Performance Status ◽  
Median Number ◽  
Study Entry ◽  
Ecog Performance Status ◽  
Overall Response

14 Background: Overall response rates of 13-19% have been reported with checkpoint inhibitor monotherapy in chemotherapy-resistant, PD-L1-positive mTNBC. RT is frequently used to enhance local control in mTNBC and has been reported to induce distant (abscopal) tumor responses when combined with immunotherapy. In this study, we evaluate the safety and efficacy of RT combined with a programmed cell death protein 1 (PD-1) inhibitor, pembro, in a single-arm, two-stage, phase II study in mTNBC. Methods: Eligible women had biopsy-proven mTNBC, ECOG performance status 0-2, and ≥2 measurable sites of metastatic disease with at least one site requiring RT. A total RT dose of 3000 cGy was delivered in 5 daily fractions. Pembro 200 mg was given intravenously within 3 days of first RT fraction, then every 3 weeks +/-3 days until disease progression. The primary endpoint was overall response rate at week 13 in the non-irradiated lesions by RECIST v1.1. Secondary endpoints included safety and overall survival. Tumor biopsies were obtained at baseline and at week 7. PD-L1 expression was not required for study entry. Results: Of the 17 women enrolled, the median age was 52 y (range 37-73y). and the median number of prior chemotherapies received for metastatic disease was 3 (range 0 to 8). Of the 8 women not evaluable at 13 weeks: 5 died secondary to disease-related complications (at weeks 2, 6, 7, 8, and 9) and 3 came off study due to disease progression prior to week 13. Of the 9 women evaluable at week 13, 3 (33%) had a partial response, 1 (11%) had stable disease and 5 (56%) had disease progression. The 3 partial responses represented 60%, 54%, and 34% decreases in tumor burden by RECIST v1.1 and were durable for 31, 21, and ongoing at 22 weeks, respectively. The stable disease response was durable for 22 weeks. Common toxicities were mild and included fatigue, myalgia and nausea. Conclusions: The combination of pembro and RT is well-tolerated. This is a poor prognosis population with 5/17 (29%) of patients dying within 12 weeks of study entry. However, durable responses were observed outside of the RT field in 3/9 (33%) patients who were unselected for PD-L1 expression and evaluable at 13 weeks. Clinical trial information: NCT02730130.

Phase II trial of everolimus in patients with previously treated recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 5541-5541 ◽  
Author(s):  
Prakash Varadarajan ◽  
Athanasios Panayotis Kotsakis ◽  
Daniel Martin ◽  
Jorge Silvio Gutkind ◽  
Michael K. Gibson ◽  
...  
Keyword(s):  
Disease Progression ◽  
Phase Ii ◽  
Primary Endpoint ◽  
Stable Disease ◽  
Plasma Levels ◽  
Phase Ii Study ◽  
Performance Status ◽  
Median Number ◽  
Post Treatment ◽  
Biomarker Analysis

5541 Background: The PI3K/Akt/mTOR pathway plays an important role in SCCHN pathogenesis and resistance to treatment. We conducted a phase II study of everolimus, an oral inhibitor of mTOR, in patients with refractory SCCHN. Methods: Patients with recurrent or metastatic SCCHN treated with at least 1 prior regimen, performance status (PS) 0-2, and adequate organ function, received everolimus 10 mg once daily orally. The primary endpoint was the disease control rate (DCR) defined as the proportion of patients with a complete response, a partial response, or stable disease. A two-stage design was followed. Cytokines were measured in plasma and serum at baseline and post treatment. Results: 9 patients were enrolled. Median age 63 years (range 51 - 82), Male/Female, 6/3, performance status 0/1/2, 2/5/1. Primary site: oropharynx (2), oral cavity (4), larynx (1), others (2). Median number of palliative therapies in the recurrent/metastatic setting prior to study was 1 (range 1- 4). Median number of cycles of everolimus delivered was 1 (range 1-5). No objective responses were seen. One patient had stable disease that lasted 6 months but all other patients had progression as best response. DCR was 11%. Median progression-free survival was 40 days. Four patients have died due to disease progression. Grade 3 adverse events were infrequent: pain (2 patients), anemia (2 patients), and 1 patient each with pruritus, hypertransaminasemia, hyponatremia, lymphopenia, and fatigue. No Grade 4 toxicities were reported. Biomarker analysis in 2 patients with available post treatment samples showed reduced plasma levels of VEGF-A, Gro-α, and IL-17, after everolimus treatment, but no reduction was observed in the plasma levels of IL-6 and IL-8, two cytokines often associated with SCCHN disease progression. Conclusions: Everolimus as monotherapy was well tolerated but did not have sufficient activity in this setting. This phase II study did not meet the predefined primary endpoint in the first stage of accrual.

Preliminary results from a single-arm, phase II study assessing the efficacy of pembrolizumab plus radiotherapy in metastatic triple negative breast cancer.

2017 ◽  
Vol 35 (7_suppl) ◽  
pp. 95-95
Author(s):  
Alice Ho ◽  
Christopher Andrew Barker ◽  
Ayca Gucalp ◽  
Lizza Lebron-Zapata ◽  
Yong Hannah Wen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Disease Progression ◽  
Phase Ii ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Phase Ii Study ◽  
Checkpoint Inhibitors ◽  
Performance Status ◽  
Ecog Performance Status ◽  
Overall Response

95 Background: Two trials have demonstrated overall response rates of 19% with immune checkpoint inhibitors alone in chemotherapy-resistant triple negative breast cancer (TNBC). Radiation therapy (RT) is frequently used to enhance local control in TNBC and has been reported to induce distant (abscopal) tumor responses when combined with immunotherapy. We evaluate the safety and efficacy of the combination of RT and pembrolizumab, a programmed cell death protein 1 (PD-1) inhibitor, in a single-arm, two-stage, phase II study in metastatic TNBC. Results from the first stage are reported. Methods: Eligibility criteria includes women with biopsy-proven TNBC, ECOG performance status 0-2, ≥ 2 measurable sites of metastatic disease with at least one site requiring RT. A total RT dose of 3000 cGy is delivered in one week in 5 fractions. Pembrolizumab is given intravenously at 200 mg/kg D1+/- 3 days and then every 3 weeks until disease progression as defined by RECIST v 1.1. The primary endpoint is overall response rate at week 13 in the non-targeted, non-irradiated lesions. Secondary endpoints include safety and overall survival. Tumor biopsies are obtained at baseline and at week 7. PD-L1 expression was not required for study entry. Results: Nine patients were enrolled in the first phase and assessed for antitumor activity and safety. Median age was 52 years (range 37-73). Three patients died secondary to disease-related complications (at weeks 2, 6 and 8) and 1 came off study due to disease progression prior to week 13. Of the 5 patients evaluable at week 13, 2 had a partial response, 1 had stable disease and 2 had disease progression. Common toxicities were mild and included fatigue, myalgia and nausea. One grade 3 event was reported - hyperbilirubinemia not attributable to study therapy after one dose of pembrolizumab. Conclusions: The combination of pembrolizumab and RT was well-tolerated in the first stage of a phase II study. Responses were observed outside of the RT fields in 2 of 5 patients who were evaluable at 13 weeks. The contribution of RT to pembrolizumab is unknown and will be investigated in the second stage of the study, which is ongoing. Correlative studies are planned. Clinical trial information: NCT02730130.

A pilot phase II study of consolidation chemotherapy with docetaxel and cisplatin following concurrent chemoradiotherapy (CCRT) for locoregionally advanced head and neck squamous cell carcinoma (HNSCC)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 5549-5549
Author(s):  
Y. Lee ◽  
S. Lee ◽  
K. Lee ◽  
S. Park ◽  
E. Cho ◽  
...  
Keyword(s):  
Disease Progression ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Performance Status ◽  
Primary Objective ◽  
Stage Iii ◽  
Pilot Phase ◽  
Consolidation Chemotherapy ◽  
Ecog Performance Status ◽  
Consolidation Phase

5549 Background: With the improvement seen with CCRT in the management of locoregionally advanced HNSCC, distant failures have become a more relevant problem in terms of survival. As a consequence, more effective strategies including consolidation chemotherapy are warranted. The primary objective of this pilot phase II study was to assess the feasibility and efficacy of docetaxel and cisplatin consolidation following primary CCRT for HNSCC. Methods: Thirty-three patients with previously untreated, stage III/IV HNSCC participated in this study. CCRT consisted of cisplatin 100 mg/m2 on day 1, 22 and 43. Concurrent radiotherapy (70 Gy) to the primary tumor and neck was performed over a period of 7 weeks. After completion of CCRT, patients with no evidence of disease progression received an additional 4 cycles of consolidation chemotherapy with docetaxel 75 mg/m2 and cisplatin 75 mg/m2 every 3 weeks. To minimize the expected accrual into unacceptable treatment, either in terms of clinical response or toxicity, a total of 35 patients would be required in a two-stage design. Results: Baseline characteristics were: male (22), median age (60 years), ECOG performance status 0/1 (15/18), stage III/IV (10/23). Of these, 27 (81%) patients completed CCRT. After CCRT, 3 complete and 19 partial responses were recorded, giving an overall response rate of 67% (95% CI, 51–83%). Of the 19 patients who went to consolidation phase, only 4 (21%) completed all 4 cycles of docetaxel and cisplatin. Failure to consolidation chemotherapy was attributed to the following causes: toxicity (11 including 3 treatment-related deaths), disease progression (4). During consolidation chemotherapy, 13 patients (68%) had grade 3/4 neutropenia and febrile neutropenia occurred in 6 (32%). With consolidation chemotherapy, one patient with initial stable disease achieved a partial response. Median survival in all patients was 11.0 months, and 8.3 months for those treated with consolidation chemotherapy. Conclusions: The poor compliance and the high incidence of severe toxicities, including 3 treatment-related deaths, prompted no further evaluation of this consolidation chemotherapy following CCRT. No significant financial relationships to disclose.

Phase II study of PX-866 in recurrent glioblastoma.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 2053-2053 ◽  
Author(s):  
Marshall W. Pitz ◽  
Elizabeth A. Eisenhauer ◽  
Mary Valeria MacNeil ◽  
Brian Thiessen ◽  
David R. Macdonald ◽  
...  
Keyword(s):  
Phase Ii ◽  
Stable Disease ◽  
Overall Response Rate ◽  
Response Rate ◽  
Phase Ii Study ◽  
Performance Status ◽  
Recurrent Glioblastoma ◽  
Pik3ca Mutations ◽  
Overall Response ◽  
Grade 3

2053 Background: Glioblastoma (GBM) is the most aggressive malignancy of the central nervous system. The majority have genetic changes that increase the activity of the phosphatidylinositol-3-OH kinase (PI3K) signal transduction pathway, critical for cell motility, proliferation, and survival. We present the results of PX-866, an oral PI3K inhibitor, in patients (pts) with recurrent GBM. Methods: A multinomial design of response and early progression (< 8 weeks on study) was used. In stage 1 (15 pts), 0 responses and ≥ 10 early progressions would stop accrual; after full accrual, ≥ 4 responses OR ≤ 13 early progressions was prespecified as of interest. Pts with histologically confirmed GBM, at first recurrence after chemoradiation and adjuvant temozolomide were given PX-866 8 mg daily on this single-arm phase II study. MRI and clinical exam were done every cycle (8 weeks). Tumour tissue was collected for analysis of potential markers of PI3K inhibitory activity (PTEN, EGFRviii, PIK3CA mutations). Results: A total of 33 pts were enrolled, eligible and evaluable. Median age was 56 (range 35-78), 12 were female; 29 had performance status (PS) 0-1 and 4 had PS 2. Median time from initial diagnosis to enrolment was 308 days (range 141-1256). Median number of cycles was 1 (range 1-7). Thirty-two pts have discontinued therapy, 26 due to disease/symptomatic progression and 6 due to toxicity (5 LFT elevation and 1 allergic reaction). Other adverse effects (AE): fatigue (16 pts/2 grade 3), diarrhea (11 pts/5 grade 3), nausea (19 pts/1 grade 3), vomiting (11 pts/1 grade 3) and lymphopenia (29 pts/7 grade 3/4). Five pts had related serious AEs (1 LFTs, 1 GI and 3 venous thromboembolism) All pts were evaluable for response; 25 had a best response of progression, 1 had partial response (overall response rate 3%) and seven (21%) had stable disease (SD, median 7.3 months; range 3.1-13.6). Six month PFS was 17%. In preliminary analyses, no statistical association was found between SD and PTEN or EGFRviii status (results pending in 16 pts). Conclusions: PX-866 was relatively well tolerated. Overall response rate was low, and the study did not meet its primary endpoint; however, 21% of pts obtained durable stable disease. Further correlative work is required to identify the predictor of this effect. Clinical trial information: NCT01259869.

Phase II study of pazopanib with weekly paclitaxel in refractory urothelial cancer.

2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 294-294 ◽  
Author(s):  
Sandy Srinivas ◽  
Sujata Narayanan ◽  
Lauren Christine Harshman ◽  
Russell Kent Pachynski ◽  
Anthony P. Lam ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Study ◽  
Performance Status ◽  
Progression Free Survival ◽  
Median Number ◽  
Upper Urinary Tract ◽  
Weekly Paclitaxel ◽  
Moderate Activity ◽  
Ecog Performance Status ◽  
Grade 3

294 Background: Currently, there are no standard treatments for relapsed or refractory urothelial carcinoma (UC). Discouraging results have been observed in trials evaluating established chemotherapeutics as single agents or in combination regimens. Paclitaxel has moderate activity when used alone and in combination in UC. Pazopanib is active in other solid tumors secondary to its potent anti-angiogenic effects. We report the results of a multi-center phase II study evaluating the combination of paclitaxel with pazopanib in refractory UC. Methods: Eligible patients (pts) had histologically confirmed UC, with disease that progressed on upto 2 chemotherapeutic regimens. Pazopanib (800 mg) was administered daily, with weekly paclitaxel (80mg/m2) for 3 weeks in a 28 day cycle. Treatment was continued until disease progression or unacceptable toxicity. The primary endpoint of the study was response-rate (RR) based on RECISTv 1.1 criteria. Secondary endpoints included safety, and progression free-survival (PFS). Results: From April 2010 to September 2014, 32 patients were enrolled. Median age was 67 years (29-89) and median ECOG performance status was 1 (0-2). 17 pts (54%) had UC of the upper urinary tract disease and 15(47%) had primary bladder tumors. All pts had multiple metastatic sites, including 9 (28%) with liver metastases. Median number of prior cytotoxic regimens was 2, and 50% were considered cisplatin responsive. Objective responses were observed in 58% with 3 (12%) complete responses (CR), and 12 pts (46%) with partial responses (PR). Another 9 (35%) acheived stable disease (SD). High grade toxicities included grade 3 hypertension (n=2), grade 3 fatigue (n=4), grade 3 thrombosis (n=2) and grade 4 neutropenia (n=2). Nearly half of the patients( n= 14 ) required growth factor support. Conclusions: Our phase II study combining paclitaxel and pazopanib demonstratedsignificant anti-tumor activity in relapsed/refractory UC. This combination is safe, effective and is worthy of evaluation in randomized phase 3 study. Clinical trial information: NCT01108055.

A phase II study of enzalutamide (Enz) with dutasteride (Dut) or finasteride (Fin) in men ≥ 65 years with hormone-naive systemic prostate cancer (HNSPCa).

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 179-179
Author(s):  
Deepak Kilari ◽  
Elizabeth A. Guancial ◽  
Deepak M. Sahasrabudhe ◽  
Kathryn A. Bylow ◽  
John D. Burfeind ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
Disease Progression ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Performance Status ◽  
Study Endpoint ◽  
Primary Study ◽  
Clinical Activity ◽  
Ecog Performance Status

179 Background: Older men are at a high risk for adverse events (AEs) from androgen deprivation therapy (ADT). In prior studies, peripheral androgen blockade with bicalutamide and Fin was better tolerated but less efficacious than ADT in HNSPCa. The potential syngerism of Enz (a potent antiandrogen) and Dut/Fin (5-a reductase inhibitors for conversion of testosterone [T] to dihydrotestosterone [DHT]) provided the rationale for this Phase II study that examined the clinical efficacy and safety of Enz with Dut/Fin in men > 65 years with HNSPCa. Methods: Eligible patients were > 65 years (y) ; at a high risk of AE from ADT by comprehensive geriatric assessment or treating physicians; had metastatic (M1) or biochemical recurrent (M0) HNSPCa with a PSA doubling time < 9 months; and had T > 50ng/dl. They received Enz (160mg daily) and Dut (0.5mg daily) or Fin (5mg daily) until disease progression according to the Prostate Cancer Working Group 2 guidelines. The primary study endpoint is time to PSA progression. The secondary endpoints are time to PSA nadir and treatment-related AEs. Results: As of July 31, 2016, 24 patients were screened (3 ineligible) and 21 were enrolled with a median follow-up of 31 weeks (7-79). Median age at enrollment was 79.5 y (66-94) and 14 %, 72% and 14% had ECOG performance status of 0, 1, and 2, respectively. 57% (n = 12) had M0 and 43% (n = 9) had M1 HNSPCa, with 18%, 62%, 5%, and 10% having Gleason 6, 7, 8, and 9 disease, respectively (5% with unkown Gleason sum). The median PSA at enrollment was 12 ng/ml (2-102). The median time to 90% PSA decline after treatment initiation was 7 weeks (7-20) and 92% achieved 80% DHT decline in 9 months. At the time of analysis, all patients had ongoing PSA decline of > 90% without radiographic evidence of disease progression. Common Grade 1 AEs included gynecomastia (28%), fatigue (28%), hot flashes (19%) and paresthesias (15%). One patient withdrew from the study due to Grade 2 paresthesia. None had Grade 3 or 4 treatment-related AEs. One patient died due to colitis unrelated to study treatments. Conclusions: Enz with Dut/Fin appears to have clinical activity for older patients with M0 and M1 HNSPCa with acceptable side effects. Clinical trial information: NCT02213107.

Phase II study of cetuximab in combination with carboplatin and docetaxel for patients with advanced/metastatic non-small cell lung cancer (NSCLC)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 7643-7643 ◽  
Author(s):  
C. P. Belani ◽  
S. Ramalingam ◽  
M. Schreeder ◽  
R. Steis ◽  
R. Guidice ◽  
...  
Keyword(s):  
Disease Progression ◽  
Phase Ii ◽  
Advanced Nsclc ◽  
Response Rate ◽  
Phase Ii Study ◽  
Performance Status ◽  
Single Agent ◽  
Stage Iiib ◽  
Duration Of Treatment ◽  
Ecog Performance Status

7643 Background: Cetuximab, a chimeric IgG1 monoclonal antibody against the external domain of the epidermal growth factor receptor (EGFR), has demonstrated single-agent activity against NSCLC. When administered in combination with carboplatin and docetaxel, a commonly used regimen for advanced NSCLC, cetuximab exhibits synergistic interaction in preclinical studies. Therefore, we conducted a phase II study to evaluate the efficacy of the combination of cetuximab, carboplatin, and docetaxel for the treatment of advanced NSCLC. Methods: Chemotherapy-naive patients = 18 years with histologically/cytologically confirmed stage IIIB (w/ effusion) or stage IV NSCLC received cetuximab (400 mg/m2 on day 1 and 250 mg/m2 on days 8 and 15) plus docetaxel (75 mg/m2 on day 1) and carboplatin (AUC=6 on day 1) every 21 days for up to 6 cycles. Thereafter, patients without evidence of disease progression (CR/PR/SD) were continued on single-agent cetuximab (250 mg/m2/week) for a maximum of 1 year or until disease progression. The primary endpoint was response rate. Results: 81 patients were enrolled and 76 are evaluable for response. Patient characteristics included: gender male/female, 43/38; median age 63 years (range 42–83); ECOG performance status 0/1/, 31/50; and stage IIIB/IV- 5/76. The median number of cycles administered was 4 (range 1–6). The response rate (CR/PR) was 14.5% (95% CI, 7.5 to 24.4), with a median progression-free survival of 4.7 months and a median overall survival of 11 months. With combination therapy, the salient grade 3/4 events were neutropenia (28%), febrile neutropenia (3.8%), hypotension (4%), hypokalemia and hypomagnesemia (5%), hypersensitivity (1%), acne-like rash (3%), peripheral neuropathy (1%), and myalgia (1%). Twenty-five patients received maintenance therapy with single-agent cetuximab (median duration of treatment was 12 weeks) and this was well tolerated. Conclusions: This large multicenter phase II study of the novel combination of cetuximab with docetaxel and carboplatin shows promising efficacy for patients with advanced and metastatic NSCLC and has an acceptable toxicity profile. No significant financial relationships to disclose.

Preliminary results of a phase II study of alrizomadlin (APG-115), a novel, small-molecule MDM2 inhibitor, in combination with pembrolizumab in patients (pts) with unresectable or metastatic melanoma or advanced solid tumors that have failed immuno-oncologic (I-O) drugs.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 2506-2506
Author(s):  
Anthony W. Tolcher ◽  
James Andrew Reeves ◽  
Meredith McKean ◽  
Bartosz Chmielowski ◽  
Joseph Thaddeus Beck ◽  
...  
Keyword(s):  
Metastatic Melanoma ◽  
Solid Tumors ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Performance Status ◽  
Nerve Sheath Tumor ◽  
Advanced Solid Tumors ◽  
Antitumor Effects ◽  
Ecog Performance Status ◽  
Multiple Tumor

2506 Background: Alrizomadlin (APG-115) restores TP53 function, activating p53-mediated apoptosis in tumor cells with wild-type TP53 and/or MDM2 amplification. Alrizomadlin also functions as a host immunomodulator and hence may restore antitumor activity in pts with cancers failing PD-1/PD-L1 blockade. Methods: This US multicenter trial assessed alrizomadlin combined with pembrolizumab in pts with unresectable/metastatic melanoma or advanced solid tumors that had failed I-O drugs; or pts with malignant peripheral nerve sheath tumor (MPNST), liposarcoma, or ATM mutant solid tumors that had failed any standard therapy. Eligible pts had ECOG performance status of 0-2 and no CNS metastases. The phase II study cohorts included pts with melanoma, NSCLC, solid tumor with ATM mutation, well-differentiated/dedifferentiated liposarcoma, urothelial carcinoma, and MPNST. Alrizomadlin was administered orally at 150 mg once every other day for 2 consecutive weeks with 1 week off and pembrolizumab at 200 mg via IV infusion for 30 minutes on Day 1 of a 21-day cycle. Results: As of December 25, 2020, 84 pts had been treated in 6 cohorts: melanoma (n = 26), NSCLC (n = 23), ATM mutation (n = 9), liposarcoma (n = 14), urothelial (n = 9), and MPNST (n = 3). In the PD-1/PD-L1 inhibitor-failed melanoma cohort, there was 1 confirmed partial response (PR) out of 5 pts with uveal melanoma, 2 PR (1 confirmed and 1 unconfirmed) of 5 pts with mucosal melanoma, and 1 confirmed PR of 11 pts with cutaneous melanoma. ORR in the melanoma cohort was 17.4% (4/23 evaluable pts), and the disease control rate was 60.9% (14/23). In the MPNST cohort, 1 of 3 pts had an unconfirmed ongoing PR. In I-O drug-failed NSCLC (n = 14 evaluable) and urothelial (n = 5 evaluable) cohorts, each reported 1 confirmed PR. Common treatment (alrizomadlin or pembrolizumab)-related adverse events (TRAEs) (≥ 10%) were nausea (63.1%), thrombocytopenia (36.9%), vomiting (33.3%), fatigue (31.0%), decreased appetite (27.4%), diarrhea (21.4%), neutropenia (15.4%), and anemia (11.9%). Grade ≥ 3 TRAEs (≥ 5%) included thrombocytopenia (20.2%), neutropenia (14.2%), and anemia (8.3%). Eleven pts discontinued treatment due to AEs: 5 were treatment related, including 2 grade 4 thrombocytopenia, and 1 each of grade 2 vomiting, grade 2 fatigue, and grade 2 posterior reversible encephalopathy syndrome (PRES). Three treatment-related SAEs were PRES, pyrexia, and asthenia. Conclusions: Alrizomadlin combined with pembrolizumab is well tolerated and may restore antitumor effects in pts with cancer resistant to or intolerant of I-O drugs, as suggested by preliminary antitumor activities in multiple tumor types. Internal study identifiers: APG-115-US-002; Keynote MK-3475-B66. Clinical trial information: NCT03611868.

A Phase II Study of Temsirolimus (CCI-779) in Patients with Advanced Leukemias.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4523-4523 ◽  
Author(s):  
Karen W.L. Yee ◽  
Guillermo Garcia-Manero ◽  
Deborah Thomas ◽  
Farhad Ravandi-Kashani ◽  
Srdan Verstovsek ◽  
...  
Keyword(s):  
Disease Progression ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Blast Crisis ◽  
Single Agent ◽  
Mammalian Target Of Rapamycin ◽  
Median Number ◽  
Prior Therapy ◽  
Flat Dose ◽  
Grade 3

Abstract Temsirolimus (CCI-779, Wyeth Pharmaceuticals) has been shown to inhibit proliferation of a variety of tumors and induce G1 cell cycle arrest by preventing activation of the serine/threonine kinase, mTOR (mammalian target of rapamycin), a downstream effector of the PI3K/Akt pathway. Several lines of evidence implicate the PI3K/Akt/mTOR pathway in hematological malignancies. Interim results of a phase II study evaluating the efficacy and toxicity of single-agent temsirolimus in patients with advanced malignancies are presented. Temsirolimus was administered weekly, at a flat dose of 25 mg, as a 30-minute intravenous infusion. Treatment was continued until evidence of disease progression or unacceptable toxicity. To date, 8 patients have been enrolled and 7 are evaluable for efficacy and toxicity (one patient did not receive temsirolimus). Of these 7 patients, 5 had AML, 1 CML-myeloid blast crisis, and 1 ALL. Median age was 68 years (range, 21 to 87 years) and 5 were male. All patients had received prior therapy, median 2 regimens (range, 1 to 3 regimens). The median number of temsirolimus doses administered was 3 (range, 1 to 10) with a median time on study of 18 days (range, 3 to 89+ days). The most common temsirolimus-related adverse events were grade ≤ 2 and consisted of anorexia, nausea and/or vomiting and diarrhea, mucositis, dermatitis, hypertriglyceridemia, hyperglycemia, hypomagnesemia, hypocalcemia, hypokalemia, hypophosphatemia, and fatigue/asthenia. No patient developed nonspecific pneumonitis. Grade 3 toxicities included fatigue/asthenia (2), hyperglycemia (1), painful mucositis with dehydration and electrolyte abnormalities (1), diarrhea with hypokalemia (1), and hypophosphatemia (1). No patient experienced grade 4 toxicities or death from temsirolimus. No patient required dose reductions, but 2 did have dose delays due to grade 3 mucositis (1) and out-of-state hospitalization for pneumonia and atrial fibrillation (1). No patient achieved a complete remission. One patient with heavily pre-treated Philadelphia-negative precursor B-cell ALL had a transient 79% to 91% reduction in peripheral blood blasts 4 days after the first dose of temsirolimus that was maintained for 12 days prior to disease progression with involvement of the synovial fluid in bilateral knees. At the time of analysis, 6 of the 7 patients have discontinued treatment due to disease progression (4), patient refusal (1), or physician decision (1). Preliminary findings indicate that temsirolimus is relatively well-tolerated at a dose of 25 mg per week and may have biologic activity in ALL. Accrual onto the study is currently ongoing.

Phase II Trial of Lenalidomide in Patients with Relapsed or Refractory Hodgkin Lymphoma

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3052-3052 ◽  
Author(s):  
John Kuruvilla ◽  
Diane Taylor ◽  
Lisa Wang ◽  
Chantale Blattler ◽  
Armand Keating ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Phase Ii ◽  
International Workshop ◽  
Performance Status ◽  
Median Number ◽  
Primary Chemotherapy ◽  
High Dose ◽  
Primary Therapy ◽  
Ecog Performance Status ◽  
Cytokine Analysis

Abstract Introduction: Patients (pts) with Hodgkin Lymphoma (HL) that has relapsed after or is refractory to primary therapy and subsequent high dose chemotherapy with autologous stem cell transplantation (ASCT) cannot be cured with conventional treatments. As various cytokines (IL-6,12 and 13), NF-KB and angiogenic factors have been implicated in the pathophysiology of HL, we postulated that lenalidomide, a novel agent with both immunomodulatory and anti-angiogenic properties would have activity in the relapsed (REL) or refractory (REF: defined as progression on or within 3 months of primary therapy) setting. Methods: The treatment regimen consisted of lenalidomide 25 mg PO days 1–21 on a 28 day cycle. CT scans of the chest, abdomen and pelvis were obtained at baseline and were repeated every 2 cycles or earlier at the investigators’ discretion. A Fleming two stage trial design was chosen and a calculated sample size of 30 was determined based on an alpha error &lt; 0.05 and power of 0.80 and a response proportion of 0.20 to consider lenalidomide active. Serum/plasma specimens at baseline and on treatment were collected for cytokine analysis. Data analysis was performed in July 2008 after the first stage (15 patients) were accrued. Responses were categorized by International Workshop Criteria (Cheson JCO 1999) and toxicity was assessed by NCI common toxicity criteria v3.0. Results: 15 pts have been accrued with 14 evaluable patients to date. The median age was 37 (range 18–74) with 7 female pts. ECOG performance status was 0: (2) 1: (9) and 2: (4). The median number of prior chemotherapy regimens was 2 (range 1–4). All pts (except one pt on a pediatric protocol had received ABVD-type primary chemotherapy and 9/15 received prior radiotherapy. 10 pts had undergone prior ASCT with 10 patients having REF and 5 pts with REL disease following primary chemotherapy. 8 pts had disease recurrence within 1 year post ASCT. Of non-ASCT pts, 2 pts were refractory to chemotherapy and 3 pts were ineligible (age and/or comorbidity). The median number of treatment cycles/pt was 3 (range 0–10) with 1 pt enrolled but not starting therapy due to rapid disease progression. Best response was a PR in 2 cases (confirmed by 3rd independent radiologist in 1), and SD in 7 pts. Six pts discontinued therapy because of PD and 5 for toxicity; 4 pts remain on treatment. Median time to progression was 3.2 months and overall survival was 9.1 months. Grade 3–4 toxicities included: neutropenia:4 (1 pt had febrile neutropenia following 1 cycle of treatment), thrombocytopenia:4 and anemia:3. Five pts developed skin rash (2: grade 2) and there was 1 case of erythema multiforme. Conclusions: Preliminary results of this phase II study including heavily pre-treated pts with HL suggest lenalidomide has some evidence of activity. Toxicity is manageable although hematologic side effects are common. These results suggest that lenalidomide warrants further study and the second stage of accrual is ongoing.

Sign in / Sign up

Export Citation Format

Share Document