A phase Ib study of telatinib (BAY 57–9352), a VEGFR-2 inhibitor, in combination with docetaxel in patients with advanced solid tumours

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 14035-14035
Author(s):  
H. M. Shaw ◽  
L. R. Molife ◽  
J. Spicer ◽  
V. Karavasilis ◽  
C. Marriott ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Partial Response ◽  
Adverse Events ◽  
Tyrosine Kinases ◽  
Fixed Dose ◽  
Advanced Solid Tumors ◽  
Toxic Dose ◽  
Phase Ib ◽  
Ecog Ps ◽  
Relevant Interaction

14035 Background: Telatinib (BAY 57–9352) inhibits VEGFR-2 and VEGFR-3 tyrosine kinases, and PDGFR-β and c-Kit. Preclinical data suggests that targeting VEGFR signaling increases antitumor activity. Methods: This trial investigated the safety, pharmacokinetics (PK), and tumor efficacy of telatinib combined with docetaxel (D). D was administered at a fixed dose of 75mg/m2 on day 1 of 21-day cycles. Telatinib was administered orally, twice daily (bid) from day 3 of Cycle 1 and onwards, thereafter continuously. Dosing of telatinib commenced at 600mg bid (cohort 1, n=6) and increased to 900mg bid (cohort 2, n=7). PK in Cycle 1 were determined on day 1 (D) and day 21 (telatinib). In Cycle 2 comparative PK profiles for both telatinib and D were sampled on days 1–3. Results: Thirteen patients (pts) with advanced solid tumors were enrolled (9M/4F; median age: 56 [range: 34–69]; ECOG PS 0/1: 3/10). A total of 69 cycles have been completed (range,1–10). Treatment-emergent adverse events of CTCAE =3 (NCI-CTC v3.0) were neutropenia (n=11, 79%), fever (n=2, 15%), and fatigue (n=2, 11%). Adverse events of CTC =3 occuring in two pts was febrile neutropenia. Others occurring in only one patient were; hypertension, ALT increase, dehydration, and reversible symptomatic pneumonitis. Study treatment-related adverse events leading to a dose reduction or interruption were neutropenia (n=5, 38%), hypertension (n=1), ALT increase (n=1), and fatigue (n=1). Two pts with prostate ca and 1 with cervical ca had a confirmed partial response. Five pts (1 NSCLC, 1 esophageal ca, 1 renal cell ca and 2 prostate ca) had stable disease for =4 cycles. Mean AUC of D increased by 48% in cohort 1, but only by 16% in cohort 2. Thus, PK data to date do not indicate a clear clinically relevant interaction between telatinib and D. Conclusions: The combination of telatinib and D was tolerated without reaching the toxic dose at telatinib 900mg bid and D 75mg/m2. This combination has demonstrated promising antitumor activity. An extension of the cohort at 900mg bid with 75mg/m2 D is being evaluated to gain further safety and PK data. No significant financial relationships to disclose.

Lurbinectedin (LUR) in combination with Irinotecan (IRI) in patients (pts) with advanced solid tumors: Updated results from a phase Ib-II trial.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 3514-3514
Author(s):  
Santiago Ponce Aix ◽  
Gregory Michael Cote ◽  
Alejandro Falcon Gonzalez ◽  
Juan Manuel Sepulveda ◽  
Elizabeth Jimenez Aguilar ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Antitumor Activity ◽  
Solid Tumors ◽  
Maximum Tolerated Dose ◽  
Fixed Dose ◽  
Advanced Solid Tumors ◽  
Phase Ib ◽  
Starting Dose ◽  
Ecog Ps ◽  
Dose Levels

3514 Background: LUR is a novel agent that exerts antitumor activity through inhibition of trans-activated transcription and modulation of tumor microenvironment. Preclinical synergism/additivity in combination with IRI has been reported, thus prompting the conduct of this clinical trial. Methods: Phase Ib-II trial to evaluate escalating doses of LUR on Day (D) 1 plus a fixed dose of IRI 75 mg/m2 on D1 and D8 every 3 weeks (q3w) in pts with advanced solid tumors (+/- G-CSF, if dose-limiting toxicities [DLTs] were neutropenia). Starting dose was LUR 1.0 m/m2 + IRI 75 mg/m2. Results: 77 pts have been treated to date at 5 dose levels, 51 of them at the recommended dose (RD). Baseline characteristics of all 77 pts were: 48% females, 68% ECOG PS=1; median age 57 years (range, 19-75 years); median of 2 prior lines (range, 0−4 lines). The maximum tolerated dose (MTD) was LUR 2.4 mg/m2 + IRI 75 mg/m2 with G-CSF, and the RD was LUR 2.0 mg/m2 + IRI 75 mg/m2 with G-CSF. DLTs in Cycle 1 occurred in 2/3 evaluable pts at the MTD and 3/13 evaluable pts at the RD, and comprised omission of IRI D8 infusion due to grade (G) 3/4 neutropenia (n=3 pts) or G2-4 thrombocytopenia (n=2). At the RD (n=51), common G1/2 non-hematological toxicities were nausea, vomiting, fatigue, diarrhea, anorexia and neuropathy. G3 non-hematological toxicities (diarrhea 10%, fatigue 10%) and G3/4 hematological abnormalities (neutropenia 49%, thrombocytopenia 10%) were transient. Conclusions: The combination of LUR and IRI had acceptable tolerance, with no unexpected toxicities. Transient myelosuppression was dose-limiting. The RD is LUR 2.0 mg/m2 on D1 + IRI 75 mg/m2 on D1 and D8 q3w with G-CSF. Antitumor activity was observed at the RD in SCLC pts, as well as in endometrial carcinoma pts. Hints of activity were also observed in STS pts. Updated results will be presented. Clinical trial information: NCT02611024 . [Table: see text]

scholarly journals O83 Phase 1 study of an anti-CD27 agonist as monotherapy and in combination with pembrolizumab in patients with advanced solid tumors

2020 ◽  
Vol 8 (Suppl 1) ◽  
pp. A2.1-A2
Author(s):  
Ronnie Shapira-Frommer ◽  
Marloes GJ van Dongen ◽  
Konstantin Dobrenkov ◽  
Elliot Chartash ◽  
Fang Liu ◽  
...  
Keyword(s):  
Adverse Events ◽  
Solid Tumors ◽  
Phase 1 ◽  
Fixed Dose ◽  
Advanced Solid Tumors ◽  
Phase 1 Study ◽  
Grade 5 ◽  
Crossover Phase ◽  
Grade 3 ◽  
Ecog Ps

BackgroundMK-5890 is a humanized agonist monoclonal antibody that binds to CD27 to provide a costimulatory signal that enhances T-cell–mediated responses. This first-in-human phase 1 study of MK-5890 evaluated the safety and efficacy of escalating doses of MK-5890 as monotherapy and in combination with pembrolizumab in patients with advanced solid tumors.MethodsKey eligibility criteria included histologically or cytologically confirmed advanced solid tumor, measurable disease by RECIST v1.1, and ECOG PS ≤1. MK-5890 was tested alone (dose range, 2-700 mg) or with pembrolizumab (fixed dose, 200 mg). Patients with disease progression following MK-5890 monotherapy were eligible to cross over to combination treatment. The primary objective was safety and tolerability. Objective response rate by investigator per RECIST v1.1 was also evaluated. The database cutoff for this analysis was May 30, 2019.ResultsOf 44 patients enrolled, 25 received MK-5890 and 19 received MK-5890 plus pembrolizumab; their median age was 59.0 years, 61.4% were female, 47.7% had ECOG PS 1, and 13.6% previously received immune checkpoint inhibitor therapy. In the initial phase, dose-limiting toxicities (DLTs) were reported in 3 patients receiving MK-5890 and 1 patient receiving MK-5890 plus pembrolizumab; all DLTs were associated with infusion-related adverse events. Maximum tolerated dose was defined. Treatment-related adverse events (TRAEs) were reported in 40 patients (90.9%): 22 patients (88.0%) receiving MK-5890 and 18 patients (94.7%) receiving MK-5890 plus pembrolizumab. The most common TRAEs were fatigue (28.0%) and infusion-related reactions (28.0%) with MK-5890 and fatigue (36.8%) and pruritus (31.6%) with MK-5809 plus pembrolizumab. Grade 3-4 TRAEs were reported in 10 patients (22.7%): 6 patients (24.0%) receiving MK-5890 and 4 patients (21.1%) receiving MK-5890 plus pembrolizumab; no grade 5 events were observed. One patient (4.0%) achieved a partial response (PR) with MK-5890 and 1 patient (5.3%) achieved a PR with MK-5890 plus pembrolizumab. Fourteen patients entered the crossover phase to receive MK-5890 plus pembrolizumab. In the crossover phase, no DLTs were reported. TRAEs were reported in 12 patients (85.7%); the most common were pruritus (21.4%), rash (21.4%), and headache (14.3%). One patient (7.1%) reported grade 3-4 TRAEs of increased amylase and increased lipase; no grade 5 events were observed. Two patients (14.3%) achieved a complete response and 2 patients (14.3%) achieved a PR.ConclusionsTreatment with MK-5890, alone and in combination with pembrolizumab, demonstrated an acceptable safety profile. Early antitumor activity was observed in patients with advanced solid tumors in both monotherapy and combination therapy arms.

287 Safety and antitumor activity of indoleamine 2,3-dioxygenase 1 (IDO-1) inhibitor KHK2455 in combination with anti-CCR4 monoclonal antibody mogamulizumab in patients with advanced solid tumors

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A313-A314
Author(s):  
Solmaz Sahebjam ◽  
Jameel Muzaffar ◽  
Timothy Yap ◽  
David Hong ◽  
Olivier Rixe ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Overall Survival ◽  
Antitumor Activity ◽  
Combination Therapy ◽  
Adverse Events ◽  
Solid Tumors ◽  
Ex Vivo ◽  
Advanced Solid Tumors ◽  
Grade 3 ◽  
Dose Dependent

BackgroundIDO-1 inhibitors have shown antitumor activity in combination with immunotherapeutic agents in multiple cancers. KHK2455 is a novel and selective oral IDO-1 inhibitor. KHK2455 inhibits IDO-1 apo-enzyme, with long-lasting and potent activity. Mogamulizumab is an anti-C-C chemokine receptor 4 (CCR4) monoclonal antibody that has shown synergy with KHK2455 in preclinical models. Mogamulizumab is approved in the US and EU for treatment of mycosis fungoides and Sézary syndrome.MethodsIn this first-in-human study, patients with advanced solid tumors received escalating oral doses of KHK2455 alone (0.3, 1, 3, 10, 30 and 100 mg once daily) for 4 weeks (Cycle 0), followed by combination with 1 mg/kg weekly of IV mogamulizumab for 4 weeks (Cycle 1), and then on Days 1 and 15 (from Cycle 2 onward) in a standard 3+3 Phase I design. Safety, tolerability, pharmacokinetics and IDO activity (kynurenine [Kyn] and tryptophan [Trp] levels and ex vivo Kyn production) were evaluated.ResultsThirty-six patients were enrolled across all cohorts. One patient with lower esophageal cancer in the 100 mg cohort exhibited dose-limiting toxicity (Grade 3 gastrointestinal necrosis). The most frequent (≥10%) treatment-emergent adverse events (TEAEs) are presented in table 1. Overall numbers of TEAEs, ≥Grade 3 TEAEs, and serious TEAEs related to KHK2455 and mogamulizumab are presented in table 2. Serious KHK2455-related TEAEs included gastrointestinal necrosis (KHK2455 monotherapy), and nausea and drug eruption (combination therapy). In addition, five drug-related TEAEs in combination therapy led to discontinuation; there were no fatal outcomes related to either study drug. Plasma KHK2455 concentrations reached steady state by Day 8 (Cycle 0) and increased dose-dependently. Potent dose-dependent inhibition of IDO activity was demonstrated by plasma Kyn concentration and Kyn/Trp ratio (median inhibition 70.5% and 70.8%, respectively, at 100 mg dose on Day 15, compared to baseline) and ex vivo Kyn production (>95% inhibition at ≥10 mg KHK2455), confirming target modulation. Six of 26 evaluable patients from all dosing groups achieved durable disease stabilization (≥6 months, RECIST 1.1), and one patient with bevacizumab-resistant glioblastoma demonstrated confirmed partial response (43.5% tumor reduction over a 2-year observation period). Median overall survival was 13.4 months, with 30% of subjects surviving for 2 years or longer (figure 1).Abstract 287 Table 1Study 2455-001: Treatment-Emergent Adverse Events (≥10% by Preferred Term)Abstract 287 Table 2Abstract 287 Figure 1Study 2455-001: Overall SurvivalConclusionsKHK2455 in combination with mogamulizumab was well-tolerated and manageable at all doses tested, suppressed Kyn production in a dose-dependent and sustained manner, and demonstrated signals of antitumor activity. These data support the continued development of this combination.AcknowledgementsMedical writing assistance was provided by Susan E. Johnson, PhD, S.E. Johnson Consulting, LLC, New Hope, PA, USA.Trial RegistrationNCT02867007 (www.clinicaltrials.gov)Ethics ApprovalThis study was approved by Ethics Committees at all participating study institutions.

scholarly journals 478 COM701 in combination with BMS-986207 (anti-TIGIT antibody) and nivolumab – preliminary results of safety, tolerability and pharmacokinetics in patients with advanced solid tumors (NCT04570839)

2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A508-A508
Author(s):  
Ecaterina Dumbrava ◽  
Manish Sharma ◽  
Gini Fleming ◽  
Kyriakos Papadopoulos ◽  
Ryan Sullivan ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Adverse Events ◽  
Solid Tumors ◽  
Pharmacokinetic Parameters ◽  
Tolerability Profile ◽  
List Type ◽  
Advanced Solid Tumors ◽  
Cancer Data ◽  
Preliminary Results ◽  
Favorable Safety

BackgroundCOM701, a novel first-in-class immune checkpoint inhibitor (ICI) binds to poliovirus receptor related immunoglobulin domain containing (PVRIG) leading to enhanced activation of T and NK-cells. COM701 in combination with nivolumab has a favorable safety profile, is well tolerated and demonstrates antitumor activity.1 We hypothesized that the addition of BMS-986207 as a triplet thereby inhibiting the DNAM axis will have an acceptable safety/tolerability profile. We present preliminary results on safety/tolerability and pharmacokinetics (PK) parameters.MethodsUsing an accelerated titration and 3+3 study design we enrolled 14 patients (pts) with advanced solid tumors. Doses of COM701 were 0.3, 1, 3, 10 or 20 [mg/kg IV Q4 wks]; in combination with nivolumab and BMS-986207 (both 480 mg IV Q4 wks). Key objectives were to evaluate the safety and tolerability, to determine the recommended dose for expansion (RDFE) and to characterize preliminary pharmacokinetic parameters. Key inclusion criteria: Age ≥ 18 yrs, histologically confirmed locally advanced or metastatic solid malignancy and has exhausted all available standard treatments. Key exclusion criteria: history of immune-related toxicities on prior immunotherapy treatment leading to discontinuation.ResultsIn the safety population [N=14], 12 pts reported treatment emergent adverse events (TEAEs). The most frequent TEAES [≥3 pts] were fatigue 5 pts (36%), pyrexia 3 pts (21%), vomiting 3 pts (21%). No DLTs were reported in any of the dose levels. The most frequent tumor types enrolled: CRC (n=3), and prostate, melanoma and OVCA/primary peritoneal cancer (n=2 each). Median number of prior therapies was 10 (range 1–19). Four pts had received prior immunotherapy. Serious adverse events [≥2 pts] were 2 pts (14%) with G3 abdominal pain, 2 pts (14%) with vomiting (1pt with G1/2 vomiting, 1 pt with G3 vomiting) all assessed by the investigator as unrelated to study drug. Preliminary PK profiles of COM701 were generally dose proportional.ConclusionsCOM701 in combination with BMS-986207 and nivolumab demonstrates a favorable safety, tolerability and PK profiles. COM701 20 mg/kg has been selected as the RDFE in combination with BMS-986207 and nivolumab (both 480 mg) all administered IV Q4 wks. The expansion cohorts are enrolling pts with platinum resistant ovarian cancer and endometrial cancer. Data cutoff 28 Jun 2021.AcknowledgementsThis study is in collaboration with Bristol Myers Squibb.Trial RegistrationNCT04570839ReferencesVaena, DA, Fleming GF et al. COM701 with or without nivolumab: Results of an ongoing phase 1 study of safety, tolerability and preliminary antitumor activity in patients with advanced solid malignancies (NCT03667716). J Clin Oncol 2021;39: (suppl 15; abstr 2504).Ethics ApprovalThe study obtained ethics approval form all the participating sites. All study participants gave informed consent before taking part.- 0002: START2020.15- 0003: 20210109- 0005: IRB20-1549- 0006: 21-060- 0007: IRB-AAAT4904- 0012: 2020-0755- 0013: STMW2020.16- 0015: 20210109

A Two-Stage Phase Ib Study to Investigate the Pharmacokinetics, Safety and Tolerability of Subcutaneous Rituximab In Patients with Follicular Lymphoma as Part of Maintenance Treatment

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2858-2858 ◽  
Author(s):  
Antonio Salar ◽  
Reda Bouabdallah ◽  
Christine McIntyre ◽  
Pakeeza Sayyed ◽  
Beate Bittner
Keyword(s):  
Adverse Events ◽  
Follicular Lymphoma ◽  
Patient Experience ◽  
Maintenance Treatment ◽  
Fixed Dose ◽  
Pharmacokinetic Parameters ◽  
Two Stage ◽  
Serious Adverse Events ◽  
Maximum Serum ◽  
Phase Ib

Abstract Abstract 2858 Rituximab-containing regimens have become the standard of care for patients suffering from various CD20-positive B-cell malignancies. Currently, rituximab is administered as an intravenous (IV) infusion over several hours. These long infusion times and the side effects related to the infusion were cited by some patients as uncomfortable consequences of the current therapeutic treatment. Furthermore, the required procedure to establish intravenous access is considered invasive and can be painful, particularly in patients with malignant diseases who are treated repeatedly. Subcutaneous (SC) administration could significantly simplify treatment, shortening administration to less than 10 minutes and improving patient experience. Recombinant human hyaluronidase (rHuPH20) has been developed and approved to improve dispersion and absorption of co-administered drugs. It has been combined with rituximab to allow injection volumes larger than 10 mL to be safely and comfortably administered SC. The aims of this Phase Ib study were to select the dose of a new SC rituximab formulation with rHuPH20 giving comparable exposure to IV rituximab and to assess its safety and tolerability in male and female follicular lymphoma (FL) patients during maintenance treatment. This presentation shows the stage 1 data of a two-stage randomized, open-label, multi-centre adaptive Phase Ib study. 124 patients have been randomized to one of four rituximab maintenance treatment groups: 16 patients IV control, 34 patients SC dose 1 [375 mg/m2], 34 patients SC dose 2 [625 mg/m2] and 40 patients SC dose 3 [800 mg/m2]. Prior to randomization, eligible patients were treated with at least one IV rituximab dose at 375 mg/m2 in the maintenance setting. For patients randomized to one of the SC cohorts, a single IV dose was replaced by an SC dose. Patients received rituximab either on a q2m or q3m regimen, as per local practice. Safety data are available from a total of 119 patients. Rituximab SC was generally well tolerated. No clinically significant observations or treatment-related serious adverse events have been reported. A total of 95 adverse events (AEs) were reported in 46 patients (39%). The most commonly documented AE was “administration-associated reaction” (AAR, including rash, erythema and mild discomfort). These AARs were reversible, predominantly mild in intensity and only 1 event necessitated any treatment (metoclopramide for nausea). Overall, the AE profile is not significantly different to that expected in patients treated with rituximab IV (after AAR, the most frequent events were gastrointestinal disorders and mild infections). Four serious adverse events (SAEs) were reported in 4 separate patients, all reported as unrelated to study medication. There were no AEs leading to death, withdrawal or treatment discontinuation. The total volume administered SC in each patient ranged between 4.4 – 15.0 mL. The average injection duration was 2 mL/min. Rituximab maximum serum concentrations in the SC cohorts occurred between Day 2 and Day 8 (48 h and 168 h). Pharmacokinetic parameters were linear with respect to dose over the range of SC doses administered (375, 625 and 800 mg/m2). Rituximab concentrations on Day 28 (C28) and the extent of serum exposure (AUC0-57) in patients administered 625 mg/m2 rituximab SC were comparable to those in patients administered the standard rituximab IV dose of 375 mg/m2 SC. In conclusion, subcutaneous rituximab can be delivered quickly, comfortably and safely while achieving serum exposure comparable to the approved intravenous formulation in FL patients during maintenance treatment. The patient experience was favourable. These results support further testing of subcutaneous rituximab and a fixed dose of 1400 mg rituximab SC has been selected for formal Ctrough non-inferiority testing in stage 2 of the trial. Disclosures: McIntyre: Hoffmann-La Roche Ltd.: Employment. Sayyed: Hoffmann-La Roche Ltd.: Employment. Bittner: Hoffmann-La Roche Ltd.: Employment.

Phase I dose escalation study of recombinant interleukin-21 (rIL-21; BMS-982470) in combination with nivolumab (anti-PD-1; BMS-936558; ONO-4538) in patients (pts) with advanced or metastatic solid tumors.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. TPS3112-TPS3112 ◽  
Author(s):  
Laura Quan Man Chow ◽  
Michael S. Gordon ◽  
Theodore F. Logan ◽  
Scott J. Antonia ◽  
Shailender Bhatia ◽  
...  
Keyword(s):  
T Cell ◽  
Antitumor Activity ◽  
Phase I ◽  
Solid Tumors ◽  
Clinical Outcomes ◽  
Dose Escalation ◽  
Fixed Dose ◽  
Weekly Schedule ◽  
Advanced Solid Tumors ◽  
Biologic Activity

TPS3112 Background: Programmed death-1 (PD-1) is an immune checkpoint receptor that attenuates T-cell activation by binding to its ligands, PD-L1 and PD-L2. Nivolumab, a PD-1 receptor blocking antibody, has shown durable antitumor activity in pts with various solid tumors in two phase I clinical trials. The cytokine rIL-21 has also shown antitumor activity in selected solid tumors. We hypothesized that combining rIL-21-induced stimulation of T-cell and NK-cell function in conjunction with T-cell checkpoint blockade using nivolumab could enhance biologic activity resulting in improved clinical outcomes, as compared with either agent alone. We describe a novel phase I study investigating the biologic activity and clinical outcomes of the combination in pts with advanced solid tumors. Methods: This ongoing study (N=160) includes a dose escalation phase (Part 1) using a 3 + 3 design followed by an expansion phase (Part 2). In Part 1 (N=60), successive pt cohorts with advanced solid tumors are being treated with escalating doses of rIL-21 (10, 30, 50, 75, or 100 µg/kg IV) on two distinct schedules (Arms A and B) in combination with fixed-dose nivolumab (3 mg/kg q 2 weeks) in 6 week cycles. Arm A administers rIL-21 on a weekly schedule, given on day 1 in weeks 1–4 of the 6 week cycle. Arm B administers rIL-21 at 3x per week during weeks 1 and 3 of the 6 week cycle. In Part 2, pts with renal cell carcinoma (N=50) or non-small cell lung carcinoma (N=50) will each be randomized to treatment at the maximum tolerated dose (MTD) or maximum administered dose, if no MTD is determined, for Arm A or Arm B. Therapy for pts who are stable or responding in Parts 1 and 2 may be continued for up to 2 years or until treatment discontinuation criteria are met. Primary objectives are to evaluate the safety of rIL-21 + nivolumab, and to define the MTD of the 2 schedules. Secondary and exploratory objectives include a preliminary assessment of the antitumor activity, pharmacokinetics, immunoregulatory activity (peripheral blood, tumor) and immunogenicity of this combination. Clinical trial information: NCT01629758.

scholarly journals Surufatinib Plus Toripalimab in Patients with Advanced Solid Tumors: A Single-Arm, Open-Label, Phase 1 Trial

2020 ◽  
Author(s):  
Yanshuo Cao ◽  
Ming Lu ◽  
Yu Sun ◽  
Jifang Gong ◽  
Jie Li ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Solid Tumors ◽  
Dose Escalation ◽  
Phase 1 ◽  
Fixed Dose ◽  
Advanced Solid Tumors ◽  
Open Label ◽  
Phase 1 Trial ◽  
Open Label Phase ◽  
Grade 3

Abstract BackgroundPreclinical studies have supported a potential synergistic antitumor activity between surufatinib and anti-programed death ligand-1 (PD-L1). We describe here the results of a single-arm, open-label phase 1 trial to evaluate the safety, preliminary efficacy, and pharmacokinetics (PK) in patients with advanced solid tumors treated with surufatinib combined with toripalimab, an inhibitor of PD-L1.MethodsThis is an open-label, dose escalation and expansion study in patients with solid tumors who had failed standard therapies or had no effective treatment. In the dose escalation stage, 3 cohorts of patients were treated with surufatinib, at dose levels of 200, 250, or 300 mg once daily (QD) in combination with a fixed dose of toripalimab 240 mg, every 3 weeks (Q3W), to evaluate maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D). Additional patients were enrolled in the dose expansion phase to further assess the efficacy, safety, and PK profile.ResultsFrom April 1, 2019 to July 10, 2020, 31 patients were screened, of which 28 patients were enrolled. One patient in the 300 mg cohort experienced dose limited toxicity (DLT), a grade 3 hyperthyroidism. The top 3 most common treatment-related adverse events of ≥ grade 3 were transaminases increased (17.9%), hypertension (14.3%) and blood bilirubin increased (10.7%). No treatment-related death or treatment discontinuation was identified. The RP2D was determined to be surufatinib 250 mg QD plus toripalimab 240 mg Q3W. Overall objective response rate was 22.2% [95% confidential interval (CI) 8.6‒42.3], and disease control rate reached 81.5% (95% CI 61.9‒93.7). ConclusionsSurufatinib plus toripalimab was well-tolerated, with no unexpected safety signals, and showed promising antitumor activity in patients with advanced solid tumors. Trial registrationclinicaltrials.gov, NCT03879057; Registered March 18, 2019, https://clinicaltrials.gov/ct2/show/NCT03879057

Phase II study of induction chemotherapy with fixed dose rate (FDR) gemcitabine and cisplatin followed by concurrent chemoradiation with capecitabine for locally advanced pancreatic cancer (LAPC)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 15122-15122
Author(s):  
J. Kim ◽  
S. Im ◽  
H. Park ◽  
E. Chie ◽  
J. Hwang ◽  
...  
Keyword(s):  
Partial Response ◽  
Induction Chemotherapy ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Additional Patient ◽  
Fixed Dose ◽  
Ecog Ps ◽  
Grade Iii

15122 Background: Despite the use of 5-FU based chemoradiotherapy (CRT) over the past decades, prognosis of patients with LAPC remains dismal. To deliver more efficient systemic treatment earlier and reduce toxicity of CRT, we designed a treatment protocol consisting of induction (IND) chemotherapy with FDR gemcitabine (GEM) and cisplatin (CDDP), followed by CRT with capecitabine (CAP) in LAPC. Methods: Eligible patients had unresectable, histologically confirmed adenocarcinoma of pancreas, ECOG PS of 0–2, and no prior chemo- or radiotherapy for this phase II study. Patients received FDR GEM 1000 mg/m2 (D1,8) and CDDP 60 mg/m2 (D1) every 3 weeks for 3 cycles. Patients without disease progression subsequently received CRT of 55.8 Gy in 31 fractions concurrently with CAP, 650 mg/m2 given twice daily without drug holidays. Four weeks after CRT, FDR GEM 1000 mg/m2 was given on day 1, 8 every 3 weeks for 3 cycles. Time to progression was the primary endpoint. Results: Between Jan 2005 and Nov 2006, 21 patients were enrolled (median age 59, M/F: 13/8, ECOG PS 0/1: 3/18). Two patients withdrew consent after 1st and 2nd cycle and remaining 19 patients completed all three cycles of IND chemotherapy, with three (15.8%) out of 19 evaluable patients achieving partial response (0 CR, 3 PR, 14 SD, 2 PD). All 17 patients completed CRT with mean radiation dose of 55.4 Gy. Further four patients progressed during CRT, while one additional patient achieved partial response. As of Jan 2007, 5 patients died and 12 patients showed tumor progression. Median TTP was 12.5 mo (95% CI: 4.2–20.8) and median survival was not reached with median follow up duration of 9.7 months. Grade III/IV toxicities included neutropenia (38.1%/9.5%), thrombocytopenia (4.8%/0%), and anemia (14.3%/0%) during IND phase. Toxicites were generally mild during CRT phase with grade III neutropenia and diarrhea occurring in one and two patients, respectively. One patient died of neutropenic sepsis after 3rd cycle of IND chemotherapy. Conclusions: FDR GEM-CDDP induction chemotherapy followed by CAP-RT and maintenance FDR GEM is feasible and active with promising TTP of 12.5 months. Enrollment continues till reaching target accrual of 37 patients. No significant financial relationships to disclose.

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