Phase Ib study of talimogene laherparepvec (T-VEC) injection into liver metastases (LMs) in combination with intravenous (IV) atezolizumab in patients (pts) with metastatic triple-negative breast cancer (TNBC) or colorectal cancer (CRC).

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. TPS725-TPS725
Author(s):  
J. Randolph Hecht ◽  
Arlene Chan ◽  
Miguel Martin ◽  
Nicolas Mach ◽  
Sara A. Hurvitz ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Performance Status ◽  
Objective Response ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Primary Objective ◽  
Intralesional Injection ◽  
Ecog Performance Status ◽  
Eligibility Criteria ◽  
The Usa

TPS725 Background: T-VEC is a genetically modified, oncolytic herpes simplex virus type 1 designed to selectively replicate within tumors and produce GM-CSF to enhance systemic antitumor immune responses. Atezolizumab is a monoclonal antibody checkpoint inhibitor (CPI) that targets PD-L1. The safety of intrahepatic administration of T-VEC has been demonstrated in a prior clinical trial (NCT02509507). A previous trial of T-VEC in combination with a CPI in advanced melanoma demonstrated improved responses compared to those with a CPI alone (Puzanov et al. JCO. 2016; 34:2619-26). We hypothesize that T-VEC combined with a CPI may also be effective in other tumor types. This phase 1b, multicenter study evaluates the safety of intrahepatic injection of T-VEC in combination with IV atezolizumab in pts with TNBC or CRC with LMs. Methods: The study will enroll up to 36 pts in two parallel cohorts (18 TNBC, 18 CRC) at sites in the USA, Europe, and Australia. The primary objective is to evaluate the incidence of dose-limiting toxicities (DLTs). Secondary objectives include objective response rate, lesion-level responses in injected and uninjected tumors, progression-free survival, and overall survival. Key eligibility criteria include age ≥ 18 years, confirmed diagnosis of TNBC or CRC with LMs, ECOG performance status 0/1, adequate organ function, disease progression during or after ≥ 1 prior standard-of-care systemic therapy for metastatic disease, and ≥ 1 measurable, injectable LM. T-VEC will be given by image-guided intralesional injection of up to 4 mL of 106 plaque forming units (PFU)/mL on day 1 and up to 4 mL of 108 PFU/mL every 21 days thereafter; atezolizumab 1,200 mg IV will be given on day 1 and every 21 days thereafter. The DLT-evaluation period is the first two cycles (1 cycle = 21 days). Interim safety analysis will occur after the first 4–6 pts have become DLT evaluable. Up to six cycles of T-VEC will be given with an additional 6 cycles allowed. After cycle three, nonhepatic lesions may be injected, subject to protocol-defined criteria. The study opened for enrollment in January 2018. (NCT03256344) Clinical trial information: NCT03256344.

Bevacizumab (Bmab) in combination with uracil-tegafur (UFT) and oral leucovorin (LV) in elderly patients (≥ 75 years old) with metastatic colorectal cancer (mCRC): A multicenter phase II trial (J-BLUE study).

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 588-588
Author(s):  
Mitsuo Shimada ◽  
Tomohiro Nishina ◽  
Jun Higashijima ◽  
Toshikazu Moriwaki ◽  
Toshiki Masuishi ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Elderly Patients ◽  
Phase Ii ◽  
Performance Status ◽  
Progression Free Survival ◽  
Open Label ◽  
Effective Treatment Option ◽  
Ecog Performance Status ◽  
Eligibility Criteria ◽  
Ecog Ps

588 Background: Now fluoropyrimidine plus Bmab is considered a recommendable option to the majority of elderly mCRC patients who are deemed inappropriate for the standard doublet chemotherapy with biologics. Our previous phase II study of UFT/ LV in elderly mCRC patients (≥75 years old) had demonstrated acceptable safety and efficacy (overall response rate [ORR] 33%, progression-free survival [PFS] 5.3 months, overall survival [OS] 18 months). The aim of the present study was to investigate the efficacy and safety of Bmab in combination with UFT/LV for elderly mCRC patients. Methods: This study was designed as a single-arm, open-label, multicenter, cooperative group (SGOSG-TCTG) clinical trial (trial registration: UMIN000003515). Key eligibility criteria included age ≥75 years, ECOG performance status (PS) 0 or 1, first-line chemotherapy, measurable lesions, and preserved organ functions. Patients received UFT 300mg/m2/day and LV 75mg/body/day on days 1-21 followed by 7 days rest, and intravenous administration of Bmab 5mg/kg on days 1 and 15. Treatment repeated every 28 days. The primary endpoint was PFS, and secondary endpoints were ORR, OS, and safety. Results: A total of 55 patients were enrolled from 15 institutions between Aug 2008 and Mar 2012. Among them, 52 eligible patients were evaluated. Median age was 80 years (range: 75-87). ECOG PS 0 was 73%. Median PFS was 8.2 months (95% confidence interval [CI], 6.2-10.3, events in 86.5%). Confirmed ORR was 40.4% (95% CI, 27.0-54.9%). Median OS was 18.7 months (95% CI, 10.3-27.0, events in 48%). The most common grade ≥3 treatment-related adverse events were hypertension (11.5%), fatigue (7.7%), nausea (5.8%), and diarrhea (5.8%). The treatment-related death occurred in 2 (3.8%) patients. Main reasons for discontinuation of treatment were disease-progression (62.5%) and toxicity (27.1%). Conclusions: Bmab in combination with UFT/LV is tolerable and effective treatment option for elderly patients (≥75 years old) with mCRC. Further trial with Bmab plus UFT/LV targeting elderly mCRC patients would be warranted. Clinical trial information: 000003515.

Final results of PEANUT: Pembrolizumab and nanoparticle albumin-bound paclitaxel (nab-paclitaxel) as salvage therapy for metastatic urothelial carcinoma (UC).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 5017-5017
Author(s):  
Patrizia Giannatempo ◽  
Giuseppina Calareso ◽  
Marco Bandini ◽  
Laura Marandino ◽  
Daniele Raggi ◽  
...  
Keyword(s):  
Performance Status ◽  
Objective Response ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Open Label ◽  
Ecog Performance Status ◽  
Repair Gene ◽  
Good Tolerability ◽  
Blood Samples ◽  
Disease Response

5017 Background: Pembrolizumab (pembro) is a new standard of care in chemotherapy (CT) pre-treated patients (pts) with metastatic UC. Nab-paclitaxel demonstrated preliminary activity in advanced UC. In the PEANUT study (NCT03464734) we investigated their combination in advanced UC after CT failure. Methods: In an open-label, single-arm, phase 2 trial, pts received 200 mg pembro, intravenously (IV), on D1 and 125 mg/m2 IV nab-paclitaxel on D1 and D8, every 3 weeks, until disease progression (PD) or unacceptable toxicity. Inclusion criteria were: predominant UC histology, failure of ≤2 platinum-based CT for metastatic disease. Response was evaluated by RECIST v.1.1 criteria every 2 cycles. Biomarkers included PD-L1 combined positive score (CPS) and comprehensive genomic profiling on tumor and blood samples (FoundationONE and FoundationACT assay). The primary endpoint was the progression-free survival (PFS). The target was to detect an improvement in the median PFS from ≤3.0 months (H0) to ≥5.0 months (H1). Results: Between 01 and 12/2019, PEANUT study enrolled 65 pts: 24% were female, median age was 69 yrs (IQR: 61-73); 25% had failed > 1 prior systemic therapies; 35% had ECOG-performance status 1; 33% had liver metastases. The median TMB was 6.9 mut/Mb. After median follow-up (FUP) of 5.5 months, 34 pts have relapsed (52.3%). The median PFS was 5 months (95%CI: 3-not reached). The 3-month PFS was 60.7% (95%CI: 49.8-74.1). The confirmed objective response-rate (ORR) was 47.7% (95%CI: 35.2-60.4): 22 partial responses and 9 complete responses (13.8%). The median duration of response was not reached, and 4 pts (6.1%) are long-term responders ( > 12 months). Grade 3 treatment-related adverse events (TRAE) were seen in 20 pts (30.7%). Most common any-grade TRAE included alopecia (76%), neutropenia (33.3%) and asthenia (33%). Neither TMB nor CPS were significantly associated with PFS on univariable analyses. In matched tumor/blood samples, objective responses were seen in 8/10 pts with PI3KCA mutations (80%); 6/10 pts with RB1 alterations (60%); 5/12 pts with DNA damage repair gene alterations (41.7%). Conclusions: Pembro-nab-paclitaxel, the first salvage CT-immunotherapy combination in UC, demonstrated a good tolerability, promising PFS and a clinically meaningful ORR in II-III line setting of advanced UC. As more mature data on biomarker selection emerges, this combination warrants additional studies in either second-line or earlier disease settings. Clinical trial information: NCT03464734 .

Phase II study of S-1 in patients with gemcitabine resistant advanced pancreatic carcinoma

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 14070-14070 ◽  
Author(s):  
K. Sudo ◽  
T. Yamaguchi ◽  
T. Ishihara ◽  
K. Nakamura ◽  
H. Saisho
Keyword(s):  
Pancreatic Carcinoma ◽  
Performance Status ◽  
Rest Period ◽  
Progression Free Survival ◽  
Primary Objective ◽  
Ecog Performance Status ◽  
Eligibility Criteria ◽  
Advanced Pancreatic Carcinoma ◽  
Grade 3 ◽  
Ecog Ps

14070 Background: S-1 is an oral fluoropyrimidine derivative with reported response rate of 21.1∼37.5% for advanced pancreatic carcinoma (Ueno, Oncology 2005; Furuse, ASCO 2005). The primary objective of this study was to assess the efficacy and safety of S-1 in patients with gemcitabine resistant advanced pancreatic carcinoma. Methods: Patients with histologically or cytologically proven, metastatic pancreatic carcinoma who had failed prior chemotherapy with gemcitabine were eligible for this study. Other eligibility criteria included an ECOG performance status (PS) of 2 or less; an age of at least 20 years; adequate organ function; and written informed consent. S-1 was administered orally at a dose of 40 mg/m2 twice daily for 28 days, followed by a 14-day rest period. Treatment was repeated every 6 weeks until disease progression. Results: Seventeen patients were enrolled with the following characteristics: median age 67 (range 40–75); male/female = 9/8; ECOG PS 0/1/2 = 1/8/8. All patients were included in analysis. Treatment was generally well tolerated and no life threatening toxicity was observed. Grade 3–4 toxicities were anorexia (17.6%) and fatigue (5.9%). Common grade 1–2 toxicities were anorexia (35.3%), anemia (35.3%), leukocytopenia (29.4%) and diarrhea (23.5%). Three patients were discontinued S-1 because of toxicities. Out of the 17 eligible patients, 3 patients (17.6%) achieved a partial response and 5 patients (29.4%) had stable disease. A marked decrease (≥50%) in tumor markers was observed in 5 (29.4%) of the patients. (CA 19–9 in 3 patients, CEA in 1 patient, DUPAN-2 in 1 patient) The median progression-free survival and the median survival time from the date of initiation of S-1 were 4.1 months (95% CI, 2.0 to 6.2 months) and 5.7 months (95% CI, 2.6 to 8.7 months), respectively. Conclusions: S-1 is well tolerated and active in patients with gemcitabine resistant advanced pancreatic carcinoma. Further investigation of this treatment appears warranted. No significant financial relationships to disclose.

Safety and efficacy of capecitabine (C) plus bevacizumab (B) as first-line in metastatic breast cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 1013-1013 ◽  
Author(s):  
G. Sledge ◽  
K. Miller ◽  
C. Moisa ◽  
W. Gradishar
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Performance Status ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Primary Objective ◽  
First Line ◽  
Ecog Performance Status ◽  
Eligibility Criteria ◽  
Grade 3

1013 Background: C alone has good activity and tolerability in metastatic breast cancer (MBC) and when combined with docetaxel improves response and survival. C combined with B in heavily pretreated MBC improved the response rate but not PFS. In untreated MBC, the addition of B to chemotherapy significantly improves progression-free survival (PFS) which suggests that B, is most effective in early disease. Methods: Primary objective of this single-arm, 2-phase study, is to evaluate PFS in MBC patients receiving first-line treatment with C 1,000 mg/m2 twice daily on days 1–15 (28 doses) and B 15 mg/kg on day 1. Treatment was repeated every 21 days until progression. Eligibility criteria included HER2-negative MBC previously untreated for metastatic disease; ECOG performance status =1; no prior anti-angiogenic or oral fluoropyrimidine therapy. A sample size of 109 patients (including dropouts) was required to give 90% power to test an improvement from 4 months median PFS to 5.6 months with the two-sided test (a 5%) Results: At data cut-off, 103 patients had received study medication. Present results are based on 103 patients (ITT population), except tumor response which is based on 91 patients who had response evaluation. The average # of cycles received in first phase is 6.8. 84 pts.are alive at this time. 38.5% (35/91) pts. have had a response: complete response 5.5%; partial response 33.0%. Stable disease is 42.9% with 81.4% clinical benefit. Planned dose received is 77.7 % for C and 99.0 % for B. The majority of adverse events (AEs) were mild or moderate. The most common grade 3 AEs were hand-foot syndrome (13%) and pain (10%); grade 4 pulmonary embolism occurred in 2% in the first phase of the study. Conclusions: Updated results with longer follow-up including toxicity, TTP and PFS will be presented at the meeting. It appears that in first-line C+B is active for MBC and is well tolerated, with few grade 3/4 toxicities. [Table: see text]

Efficacy of concurrent cetuximab (CTX) and nivolumab (NIVO) in previously untreated recurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 6017-6017
Author(s):  
Christine H. Chung ◽  
Nabil F. Saba ◽  
Conor Ernst Steuer ◽  
Jiannong Li ◽  
Priyanka Bhateja ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Performance Status ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Infusion Reaction ◽  
Unknown Primary ◽  
Current Standard ◽  
Ecog Performance Status ◽  
Common Grade ◽  
Grade 3

6017 Background: Current standard of care for patients (pts) with previously untreated R/M HNSCC that are incurable is either pembrolizumab (pembro) with/without chemotherapy depending on the Programmed Death-Ligand 1 (PD-L1) combined positive score (CPS). We evaluated the combination of CTX and NIVO for its efficacy. Methods: Pts were treated with CTX 500 mg/m2 IV on Day (D) -14 as a lead-in followed by CTX 500 mg/m2 IV and NIVO 240 mg/m2 IV on D1 and D15 every 28-D cycle (C). Pts with CTX infusion reaction or who did not receive C1D1 for any reason were non-evaluable and replaced. NIVO dose reduction was not allowed. Results: Fifty-four evaluable pts were analyzed. Median age was 62 (42-85). ECOG performance status at baseline was 0 (20, 37%), 1 (30, 56%), and 2 (4, 7%). Primary sites were oral cavity 19 (35%), oropharynx 22 (41%), hypopharynx 3 (6%), larynx 9 (17%), and unknown primary 1 (2%). p16 status is positive 22 (41%), negative 29 (54%), and unknown 3 (6%). PD-L1 CPS is < 1 in 6 (11%), >1 in 26 (48%), and unknown 22 (41%). Median follow up time for overall survival (OS) was 12.2 months. The most common grade 3 treatment-related adverse events (TRAEs) occurring in ≥2 pts were hypomagnesemia 2 (4%), hypophosphatemia 2 (4%), fatigue 4 (7%), and rash-acneiform 4 (7%). The only grade 4 TRAEs were hypomagnesemia in 1 (2%) and CTX infusion reaction in 1 (2%). The most common grade 3 immune-related adverse event (IRAE) occurring in ≥2 was fatigue 2 (4%). No grade 4 IRAEs is observed. Median progression-free survival (PFS) and OS were 7.8 and 14.5 months, while 1-year PFS and 1-year OS were 39% and 61%, respectively. There were no statistically significant differences in either PFS and OS based on tumor p16 or PD-L1 status. Conclusions: The clinical trial met its primary endpoint of 1-year OS. Our data indicate the combination of CTX and NIVO is safe and effective in pts with previously untreated incurable R/M HNSCC. Clinical trial information: NCT03370276.

Phase II trial of single-agent ganetespib (STA-9090), a heat shock protein 90 (Hsp90) inhibitor in heavily pretreated patients with metastatic castration-resistant prostate cancer (mCRPC) post docetaxel-based chemotherapy: Results of a Prostate Cancer Clinical Trials Consortium (PCCTC) study.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 5085-5085 ◽  
Author(s):  
Elisabeth I. Heath ◽  
Mark N. Stein ◽  
Ulka N. Vaishampayan ◽  
Emmanuel S. Antonarakis ◽  
Glenn Liu ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Trial ◽  
Cancer Cells ◽  
Performance Status ◽  
Single Agent ◽  
Progression Free Survival ◽  
Primary Objective ◽  
Castration Resistant Prostate Cancer ◽  
Ecog Performance Status ◽  
Stage 1

5085 Background: Hsp90 is a molecular chaperone required for the proper folding and activation of numerous client proteins and is critical to cell survival and proliferation. Ganetespib (G), a synthetic small molecule that binds to the ATP pocket in the N-terminus of Hsp90 causes the degradation of cellular proteins and ultimately death of cancer cells dependent on these proteins. G displays potent anticancer activity in prostate cancer cells. Methods: Eligible patients were ≥ 18 yrs old with ECOG performance status ≤ 2. Adequate hepatic, renal, and bone marrow function was required. Patients were treated with G 200 mg/m2 intravenously once weekly for 3 consecutive weeks followed by 1 off-week. The primary objective was to evaluate the 6-month progression-free survival (PFS). Secondary endpoints included overall safety and tolerability of G and overall survival. Exploratory markers including maspin, cytokeratins 8 and 18, and HDAC1 were obtained pre, during, and post G treatment. We sought ≥ 4 patients with ≥ 6 months PFS (a success) in Stage 1 of a 2-stage near-optimal Simon design. Results: 18 patients were enrolled at 4 institutions. The patients’ median age was 68 (range 51-82), 13 were Caucasian, 4 were African American, and 1 was Asian. Median PSA was 210.7 ng/mL (range 25.9 – 3,489 ng/mL). One patient never started therapy. Among the 17 treated patients, the median number of cycles was 2 (range 1-5). The most frequent Grade 3 toxicities were diarrhea (3 patients), fatigue (3), and dehydration (3). Prior therapy included abiraterone (8), sipuleucel-T (4), and other targeted therapy (4). With < 4 successes in Stage 1, the trial was terminated early. Median PFS was 1.9 months (90% CI: 1.7 – 2.7 months); median OS was 10.2 months (90% CI: 2.3 – 18.3 months). Exploratory markers have been evaluated and will be presented. Conclusions: Our study represents the first clinical trial of G in treating mCRPC patients. As a single agent therapy, G did not prolong PFS. Combination therapy is a consideration to improve therapeutic efficacy. Clinical trial information: NCT01270880.

Tremelimumab in combination with durvalumab in first or second-line mesothelioma patients: Safety analysis from the phase II NIBIT-MESO-1 study.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 8558-8558 ◽  
Author(s):  
Luana Calabro ◽  
Aldo Morra ◽  
Diana Giannarelli ◽  
Giovanni Amato ◽  
Erica Bertocci ◽  
...  
Keyword(s):  
Phase Ii ◽  
Liver Toxicity ◽  
Performance Status ◽  
Objective Response ◽  
Progression Free Survival ◽  
Safety Analysis ◽  
Primary Objective ◽  
Second Line ◽  
Open Label ◽  
Ecog Performance Status

8558 Background: The anti-CTLA-4 tremelimumab at two different dose-schedules of administration showed promising activity in second-line malignant mesothelioma (MM) patients (Calabrò et al., Lancet Oncol, 2013; Calabrò et al., Lancet Respir Med, 2015). These initial results and the efficacy of targeting the PD-1/PD-L1 axis in different tumor types, prompted the NIBIT-MESO-1 study aimed at investigating the efficacy and safety of tremelimumab combined with the anti-PD-L1 durvalumab in mm patients. We report the safety analysis from the fully-enrolled NIBIT-MESO-1 study. Methods: The NIBIT-MESO-1 is a phase II, open-label, single Center study. Forty mm patients received tremelimumab at 1 mg/Kg i.v. every 4 weeks (Q4W) for 4 doses, and durvalumab at 20 mg/Kg i.v. Q4W for 13 doses. Primary objective is immune-related (ir)-objective response rate; secondary are safey, ir-disease control rate, ir-progression free survival, and overall survival. Tumor assessment per ir-modified RECIST or ir-RECIST 1.1 for pleural or peritoneal MM, respectively, was performed at baseline and q12 weeks. Adverse events (AEs) were recorded according to CTC v4.0. (ClinicalTrials.gov Id: NCT02588131). Results: From October 2015 to October 2016, 40 mm patients (38 pleural and 2 peritoneal), median age 64 years (range 41-80), ECOG performance status 0 (n = 19) or 1 (n = 21) were enrolled in the study. mm histology was epithelioid (n = 32), biphasic (n = 5), sarcomatoid (n = 2) or undefined (n = 1). As of January 2017, 12 first or 28 second-line mm patients received a median of 5.5 doses of therapy (range = 1-13). Twenty-four patients (60%) experienced any grade irAEs: 5 patients (12.5%) had grade 3-4 AEs, the most frequent being hepatotoxicity (7.5%). AEs were generally manageable and reversible per protocol guidelines. Three patients (7.5%) were discontinued due to treatment-related AEs (1 trombocytopenia, 1 limbic encephalitis, 1 liver toxicity). Conclusions: The combination of tremelimumab and durvalumab is safe and manageable in mm patients. Clinical trial information: NCT02588131.

Interim results of PEANUT: pembrolizumab and nanoparticle albumin-bound paclitaxel (nab-paclitaxel) as salvage therapy for metastatic urothelial carcinoma (UC).

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 494-494
Author(s):  
Andrea Necchi ◽  
Daniele Raggi ◽  
Marco Bandini ◽  
Elena Farè ◽  
Patrizia Giannatempo ◽  
...  
Keyword(s):  
Performance Status ◽  
Objective Response ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Study Endpoint ◽  
Open Label ◽  
Ecog Performance Status ◽  
Blood Samples ◽  
Disease Response ◽  
Line Setting

494 Background: Pembrolizumab (pembro) is a new standard of care in chemotherapy (CT) pre-treated patients (pts) with metastatic UC. Nab-paclitaxel (nPtx) demonstrated preliminary activity in advanced UC. In the PEANUT study (NCT03464734) we investigate their combination in advanced UC after CT failure. Methods: In an open-label, single-arm, phase 2 trial, pts receive 200 mg pembro, intravenously (IV), on D1 and 125 mg/m2 IV nPtx on D1 and D8, every 3 weeks, until disease progression (PD) or onset of unacceptable toxicity. Key inclusion criteria are: predominant UC histology, failure of ≤2 platinum-based CT for metastatic disease. Response is evaluated by RECIST v.1.1 criteria every 2 cycles. Biomarkers include PD-L1 expression with the combined positive score (CPS) and comprehensive genomic profiling on tumor and blood samples (FoundationONE and FoundationACT assay). The primary endpoint of the study is the progression-free survival (PFS). The target is to detect an improvement in the median PFS from ≤3.0 months (H0) to ≥5.0 months (H1). Results: Between 01 and 08/2019, PEANUT enrolled 46 pts evaluable for the study endpoint: 26% female, median age 66 y (range 43-78); 70% had failed 1 prior systemic therapy vs 30% 2 prior therapies; 24% had ECOG-performance status 1; 28% had liver metastases. The median TMB was 6.9 mut/Mb. After median follow-up of 5 months, 18 pts have relapsed (39%). The projected median PFS was 7 months (95%CI: 4-not achieved). The confirmed objective response-rate (ORR) was 47.8% (95%CI: 32.9-63.1): 18 partial responses and 4 complete responses (8.7%). Grade 3 treatment-related adverse events (TRAE) were seen in 6 pts (13%). Most common any-grade TRAE included alopecia (91%), asthenia (21.7%), and neutropenia (15%). Neither TMB nor CPS were significantly associated with PFS on univariable analyses. 7/8 pts with PI3KCA mutations in matched tumor/blood samples had an objective response (87.5%). Conclusions: Preliminary results from PEANUT study demonstrated a promising PFS and a clinically meaningful ORR in II-III line setting of advanced UC. Updated data, including mature PFS, duration of response and biomarkers will be presented. Clinical trial information: NCT03464734.

PEAK (study 20070509): A randomized phase II study of mFOLFOX6 with either panitumumab (pmab) or bevacizumab (bev) as first-line treatment (tx) in patients (pts) with unresectable wild‑type (WT) KRAS metastatic colorectal cancer (mCRC).

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 446-446 ◽  
Author(s):  
Lee Steven Schwartzberg ◽  
Fernando Rivera ◽  
Meinolf Karthaus ◽  
Gianpiero Fasola ◽  
Jean-Luc Canon ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Study ◽  
Performance Status ◽  
Objective Response ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Ecog Performance Status ◽  
Eligibility Criteria ◽  
Prior Therapy ◽  
Randomized Phase Ii

446 Background: Pmab has demonstrated significant improvement in progression-free survival (PFS) in pts with WT KRAS mCRC as 1st-line tx in a phase III trial comparing pmab + FOLFOX4 vs FOLFOX4 alone. Here, we describe the results of PEAK, a multicenter, randomized phase II study evaluating pmab + mFOLFOX6 and bev + mFOLFOX6 in pts with previously untreated WT KRASmCRC. Methods: Pts were randomized 1:1 to pmab 6.0 mg/kg + mFOLFOX6 Q2W or bev 5.0 mg/kg + mFOLFOX6 Q2W. Pt eligibility criteria included: WT KRASmCRC, ECOG performance status ≤ 1, and no prior chemotherapy, anti-VEGF tx, or anti-EGFR tx for mCRC. The primary endpoint was PFS; secondary endpoints included overall survival (OS), objective response rate (ORR), and safety. No formal hypothesis was tested. Results: 285 pts with WT KRASmCRC were randomized and 278 pts received tx. Demographics were balanced between arms. Intent-to-treat efficacy results are shown (Table). Worst grade 3/4 adverse events (AE) occurred in 86% of pts in the pmab + mFOLFOX6 arm vs 76% of pts in the bev + mFOLFOX6 arm. Grade 5 AEs occurred in 5% of pts in the pmab + mFOLFOX6 arm and 6% of pts in the bev + mFOLFOX6 arm. Tx discontinuation due to any AE was 24% in the pmab + mFOLFOX6 arm and 27% in the bev + mFOLFOX6 arm. Conclusions: In this estimation study of pts with WT KRASmCRC without any prior therapy for mCRC, PFS and ORR were similar between arms. The median OS was not reached in the pmab + mFOLFOX6 arm. The safety profile for both arms was consistent with previously reported studies of either combination. Tx discontinuation rates due to AEs were similar between arms. Clinical trial information: NCT00819780. [Table: see text]

A phase I/II study of HB-201, an arenavirus-based cancer immunotherapy, alone, or in combination with anti-PD-1 in patients with HPV16+ cancers.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. TPS3171-TPS3171
Author(s):  
Bharat Burman ◽  
Jiaxin Niu ◽  
Rom S. Leidner ◽  
Ding Wang ◽  
Debra L. Richardson ◽  
...  
Keyword(s):  
Phase I ◽  
Phase Ii ◽  
Metastatic Cancer ◽  
Performance Status ◽  
Treatment Options ◽  
Progression Free Survival ◽  
Primary Objective ◽  
Ecog Performance Status ◽  
Eligibility Criteria ◽  
Cancer Disease

TPS3171 Background: Human Papillomavirus 16 (HPV16) is linked to several cancer types; treatment options are limited for patients with HPV16+ recurrent or metastatic cancers. The generation and maintenance of the HPV16+ malignant state requires the stable expression of HPV16-specific E7 and E6 oncogenes, which can also serve as immunogenic tumor-associated antigens. HB-201 is a replication-competent live-attenuated vector based on the arenavirus LCMV encoding a non-oncogenic E7 and E6 fusion protein. In preclinical models, both intravenously (IV) and intratumorally (IT) administered HB-201 demonstrate potent immunogenicity by induction of HPV16-specific cytotoxic T cells and associated efficacy. Methods: This is a first in human, Phase I/II study of HB-201 monotherapy or in combination with PD-1 immune checkpoint inhibitor (anti-PD-1) in HPV16+ confirmed recurrent/metastatic cancers. Phase I consists of 2 treatment groups, each conducted with a 3+3 dose escalation design. Group 1 is enrolling patients with HPV16+ head and neck squamous cell carcinoma who will receive HB-201 IV only. Group 2 is enrolling HPV16+ cancer patients with a safely accessible tumor site who will receive HB-201 IT for the first dose, followed by HB-201 IV for subsequent doses (IT-IV). HB-201 will be administered every 21 days. The Phase II component will be conducted with the recommended Phase II doses (RP2Ds) defined in Phase I and will consist of 3 groups: Group A (HB-201 IV only), Group B (HB-201 IV plus anti-PD-1), and Group C (HB-201 IT-IV). Key eligibility criteria include age > 18, ECOG performance status 0-1, confirmed HPV16+ recurrent or metastatic cancer, disease progression from at least 1 systemic standard of care therapy, and measurable disease per RECIST v1.1. The Phase I primary objective is to determine RP2Ds for IV and IT HB-201. The Phase II primary objective is to assess antitumor activity. Secondary endpoints for both phases include safety, tolerability, overall survival, progression-free survival, and duration of response. Exploratory objectives include characterization of immunogenicity of HB-201 and biomarkers associated with immune or antitumor response. Enrollment to Groups 1 and 2 began in December 2019. Clinical trial information: NCT04180215 .

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