Recurrence-free survival (RFS) and objective response rate (ORR) phase 1/2 study of intralesional (IL) neoadjuvant (neo) anti-PD1 agents (aPD1) for stage IIIB-IV melanoma (MEL).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e14171-e14171
Author(s):  
Igor Samoylenko ◽  
Olga V. Korotkova ◽  
Ekaterina Shakhray ◽  
Tatiana Zabotina ◽  
Sergey Berdnikov ◽  
...  
Keyword(s):  
Phase 1 ◽  
Objective Response ◽  
Tumor Infiltrating Lymphocytes ◽  
Residual Tumor ◽  
Primary Analysis ◽  
Stage Iiic ◽  
Unresectable Stage ◽  
Biomarker Analysis ◽  
Expansion Cohort ◽  
Infiltrating Lymphocytes

e14171 Background: We previously reported that aPD1 agents could be safely administered IL in patients (pts) with metastatic MEL with superficial lesions, providing local and bystander tumor response (Samoylenko, I., et al. (ASCO-SITC 2018)). We present results from an interim 6 mos analysis of RFS and ORR for IL neo aPD1 therapy. Methods: Pts with unresectable stage IIIC/D/IVM1a-c MEL (safety cohort, N = 7) and resectable stage IIIC/D/IVM1a (expansion cohort, N = 18), with ≥ 1 injectable cutaneous, subcutaneous, or nodal lesions ≥ 10 mm were allocated to 6 doses/12 of nivolumab or pembrolizumab before surgery (surg). aPD1 was given at scale-based dosing regimen reported previously. Tumor sampling for biomarker analysis and pCR confirmation (or core-needle biopsy, CNB) was performed prior to treatment and at week 13-18. The analysis was conducted on the ITT basis to estimate RFS at 6 mos and ORR. An RFS event was defined as disease progression or death due to any cause after surg and assessed in the expansion cohort. ORR for the both cohorts was evaluated. Results: Since Apr 2016 to Dec 2018 25 pts were enrolled. Baseline characteristics are summarized in Table. ORR was 47,6% (10/21 pts assessed), with 5 (24%) clinical CR and 4 pathological CR (19%). Among 18 pts considered for surg 2 refused from surg when CNB confirmed no residual tumor. 89% of pts (16/18 pts) from the expansion cohort remained recurrence free at 6 mos FU. Baseline immune phenotype of tumor infiltrating lymphocytes (TILs) was available for 20 of 21 pts assessed. Baseline percent of TILs assessed by flow cytometry (FCT) was higher in responders vs non-responders (7.54±7.51% vs 1.51±2.93, p < .05), whereas CD3-CD16+CD56+ and CD4+CD25+ values were lower in responders vs non-responders (0.94±1.45% vs 7.88±6.84, p < .05, and 6.68±3.46% vs 20.50±16.79, p < 0.05, respectively). PD1, PDL-1 and PDL-2 expression in tumor cells and TILs assessed by FCT did not differ significantly between responders and non-responders. Conclusions: We demonstrated the potential clinical efficacy of IL aPD1 in melanoma pts. Further studies are needed to determine if unsuccessful IL administration could predict failure to adjuvant treatment. Primary analysis of RFS at 1-yr is expected. Clinical trial information: NA. [Table: see text]

scholarly journals 353 Safety and efficacy of tumor infiltrating lymphocytes (TIL, LN-145) in combination with pembrolizumab for advanced, recurrent or metastatic HNSCC

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A378-A378
Author(s):  
Antonio Jimeno ◽  
Sophie Papa ◽  
Missak Haigentz ◽  
Juan Rodríguez-Moreno ◽  
Julian Schardt ◽  
...  
Keyword(s):  
Cell Therapy ◽  
Checkpoint Inhibitors ◽  
Adoptive Cell Therapy ◽  
Single Agent ◽  
Objective Response ◽  
Tumor Resection ◽  
Tumor Infiltrating Lymphocytes ◽  
Open Label ◽  
Safety And Efficacy ◽  
Infiltrating Lymphocytes

BackgroundSingle agent checkpoint inhibitors (CPI) are an approved first or second-line therapy in head and neck squamous cell carcinoma (HNSCC), but their efficacy is limited. Adoptive cell therapy with tumor infiltrating lymphocytes (TIL, LN-145) has demonstrated efficacy in multiple malignancies alone or in combination with CPI. To improve HNSCC therapy, a combination of pembrolizumab and LN-145 was explored.MethodsIOV-COM-202 is an ongoing Phase 2 multicenter, multi-cohort, open-label study evaluating LN-145 in multiple settings and indications, and here we report cohort 2A which enrolled CPI naïve HNSCC patients who received the combination of LN-145 and pembrolizumab. Key eligibility criteria include up to 3 lines of prior therapy, ECOG <1, at least one resectable metastasis for LN-145 production, and at least another measurable lesion after tumor resection. Primary endpoints are ORR per RECIST v1.1 by investigator and safety as measured by the incidence of grade ≥ 3 treatment-emergent adverse events (TEAEs). LN-145 production method uses central GMP manufacturing in a 22-day process yielding a cryopreserved TIL product (figure 1). Preconditioning chemotherapy consists of cyclophosphamide/fludarabine, followed by LN-145, and then < 6 doses of IL-2 over <3 days. Pembrolizumab is initiated post-tumor harvest but prior to LN-145 and continues after LN-145 infusion Q3W until toxicity or progression (figure 2).ResultsNine (N=9) HNSCC patients have received LN-145 plus pembrolizumab, with a median duration of follow up of 6.9 months. Nine and 8 patients were evaluable for safety and efficacy, respectively. Mean number of prior therapies was 1.1 with 89% of the patients having received prior chemotherapy. Four were HPV+, 2 HPV-, 3 unknown. The Treatment Emergent Adverse Event (TEAE) profile was consistent with the underlying advanced disease and the known AE profiles of pembrolizumab, the lymphodepletion and IL-2 regimens. The most common TEAE were chills, hypotension, anemia, thrombocytopenia, pyrexia, fatigue and tachycardia. Four patients had a confirmed, objective response with an ORR of 44% (1 CR, 3 PR, 4 SD, 1 NE) per RECIST 1.1. The disease control rate at data cutoff was 89% in 9 patients, and 7 of the 8 evaluable patients (87.5%) had a reduction in target lesions. Median DOR was not reached.Abstract 353 Figure 1Iovance LN-145 (autologous TIL cell therapy product) ManufacturingAbstract 353 Figure 2IOV-COM-202 Study SchemaConclusionsLN-145 can be safely combined with pembrolizumab in patients with metastatic HNSCC. LN-145 plus pembrolizumab shows early signs of improved efficacy particularly when compared with literature reports of pembrolizumab alone in a comparable patient population. Enrollment is ongoing and updated data will be presented.Trial RegistrationNCT03645928Ethics ApprovalThe study was approved by Advarra Institutional Review Board, under protocol number: Pro00035064.

Paclitaxel once weekly (wP) combined with fixed dose of oral metronomic cyclophosphamide (OMC): A dose-escalating phase I trial.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e14015-e14015
Author(s):  
Diane Pannier ◽  
Antoine Adenis ◽  
Emmanuelle Tresch-Bruneel ◽  
Emilie Bogart ◽  
Farid El Hajbi ◽  
...  
Keyword(s):  
Dose Escalation ◽  
Phase 1 ◽  
Objective Response ◽  
Fixed Dose ◽  
Hematological Toxicity ◽  
Phase 2 ◽  
Growth Modulation ◽  
Primary Tumors ◽  
Combination Methods ◽  
Expansion Cohort

e14015 Background: OMC, as continuous administration of low doses of chemotherapy acts as direct cytotoxic as well as antiangiogenetic agent. wP also induces antiangiogenic effects in mouse models. The aims of this trial were to determine the recommended Phase 2 dose (RP2D) of wP given in combination with OMC, and estimate activity and safety of the combination. Methods: Methods This is a single-center, phase 1 trial. Patients (pts) > 18 years with refractory metastatic cancers were eligible if no standard curative measures existed. Paclitaxel was administered IV weekly (D1, D8, D15; D1 = D28) in combination with a fixed dose of OMC (50mg x2/day). A 3+3 design was used for Dose-Escalation of wP (40 mg/m² to 75 mg/m²), followed by an expansion cohort at RP2D. The primary endpoint was the dose-limiting toxicity (DLT), defined as grade > 3 non-hematological or grade 4 hematological toxicity (NCI-CTCAE v4.0) occurring in the first 28 days, or any toxicity leading to a dose reduction. Results: 28 pts (18 in dose-escalation phase and 10 in expansion cohort) were included between May 2011 and December 2013. The sex ratio was 2:1, the median age was 54.5 (range, 26-67); the most common primary tumors were colorectal cancers (n = 9), sarcomas (n = 4), Head & Neck (n = 3). 16/18 pts enrolled in the dose-escalation phase were evaluable for DLT. DLT occurred in 0/3, 1/6 (neuropathy), 0/3 and 2/4 pts (hematological toxicity) at dose 40, 60, 70 and 75 mg/m² of wP, respectively. The RP2D of wP was 70 mg/m2; 1/10 pts in the expansion phase had an hematological DLT. At RP2D (n = 14), the maximal grade of adverse events (AE), regardless of causality, was Gr2 in 3 pts, Gr3 in 7 pts, Gr4 in 3 pts and Gr5 in 1 pt; the maximal grade of treatment-related AE was Gr1 in 1 pt, Gr2 in 8 pts, Gr3 in 3 pts and Gr4 in 1 pt (no AE in 1 pt). At RP2D, the median PFS was 2.8 mo and Growth Modulation index was ≥1.33 in 4/14 pts (29%). There was 1 objective response (1/14; 7%): 1 pt with lung adenocarcinoma achieved a partial response. Conclusions: The combination of OMC and wP resulted in an acceptable safety profile. Further evaluation of this combination with wP at 70mg/m² could be warranted in a phase 2 trial. Clinical trial information: NCT01374620.

Primary analysis of phase 2 results of cemiplimab, a human monoclonal anti-PD-1, in patients (pts) with locally advanced cutaneous squamous cell carcinoma (laCSCC).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 6015-6015 ◽  
Author(s):  
Michael Robert Migden ◽  
Nikhil I. Khushalani ◽  
Anne Lynn S. Chang ◽  
Danny Rischin ◽  
Chrysalyne D. Schmults ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Median Duration ◽  
Phase 1 ◽  
Objective Response ◽  
Locally Advanced ◽  
Primary Objective ◽  
Phase 2 ◽  
Primary Analysis ◽  
Curative Surgery ◽  
Grade 3

6015 Background: Cemiplimab (REGN2810) produced substantial antitumor activity with durable responses in Phase 1 CSCC expansion cohorts and Phase 2 metastatic (m) CSCC cohort. We now present the primary analysis of the Phase 2 laCSCC cohort (NCT02760498; data cutoff date: Oct 10, 2018). Methods: Pts with laCSCC received cemiplimab 3 mg/kg IV every 2 weeks (Q2W). Tumor measurements were performed Q8W. The primary objective was to evaluate objective response rate (ORR; complete response [CR] + partial response [PR]) according to independent central review (per RECIST 1.1 for scans; modified WHO criteria for photos). Results: 78 pts were enrolled (59 M/ 19 F; median age: 74 years; ECOG PS: 0 in 38 pts, 1 in 40 pts; primary CSCC site: head/neck in 79.5%; prior systemic therapy: 15.4%; prior radiotherapy: 55.1%). Median duration of follow-up was 9.3 months (range: 0.8–27.9). ORR by central review was 43.6% (95% CI: 32.4–55.3; 10 CRs and 24 PRs); investigator-assessed (INV) ORR was 52.6% (95% CI: 40.9–64.0; 13 CRs and 28 PRs). Median duration of response (DOR) has not been reached. The longest DOR at data cut-off was 24.2 months and was still ongoing. Durable disease control rate (stable disease or response for ≥16 weeks) was 62.8% (95% CI: 51.1–73.5). Median observed time to response was 1.9 months (range: 1.8–8.8). Median progression-free and overall survival have not been reached. Tumor PD-L1 status is available for 48/78 pts, tumor mutational burden analysis (from targeted exome panel) is ongoing for ≥40/78 pts; response correlation analyses are planned. The most common treatment-emergent adverse events (AEs; all grades, Grade ≥3) were fatigue (42.3%, 1.3%), diarrhea and pruritus (both 26.9%, 0%), and nausea (21.8%, 0%). INV grade ≥3 immune-related AEs occurred in 10.3% of pts. One pt died due to an unknown cause that was assessed as treatment-related. Conclusions: Cemiplimab 3 mg/kg Q2W showed substantial antitumor activity, durable responses, and acceptable safety profile in pts with laCSCC. These data strongly support the recent FDA approval of cemiplimab-rwlc for pts with mCSCC or laCSCC who are not candidates for curative surgery or curative radiation. Clinical trial information: NCT02760498.

An open label, multicenter, phase I/II study of RP1 as a single agent and in combination with PD1 blockade in patients with solid tumors.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. TPS2671-TPS2671
Author(s):  
Mark R. Middleton ◽  
Joseph J. Sacco ◽  
Jaime R. Merchan ◽  
Brendan D. Curti ◽  
Ari M. Vanderwalde ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Phase I ◽  
Solid Tumors ◽  
Dose Escalation ◽  
Phase 1 ◽  
Single Agent ◽  
Objective Response ◽  
Phase 2 ◽  
Biomarker Analysis ◽  
Tumor Types

TPS2671 Background: RP1 is an attenuated oncolytic HSV-1 that expresses a fusogenic glycoprotein from gibbon ape leukemia virus (GALV-GP R-) and GM-CSF. RP1 induces potent GALV-GP R- enhanced immunogenic cell death and host anti-tumor immunity in murine tumor models and increases PD-L1 expression. This clinical trial (NCT03767348) was designed to test the hypotheses that RP1 is safe when given alone and together with nivolumab (phase 1) and has efficacy together with nivolumab in four tumor types (phase 2). Methods: The primary goals of this clinical trial in a total of ~150 patients are to define the safety profile of RP1 alone and together with nivolumab, determine the recommended phase 2 dose (phase 1), and then in four phase 2 cohorts, to determine objective response rate in patients with melanoma, non-melanoma skin cancer, urothelial carcinoma and MSI-H solid tumors. Secondary objectives include duration of response, CR rate, PFS, viral shedding, and immune biomarker analysis. Patients with advanced cancer who failed prior therapy were eligible for the phase I component. In Phase 2 patients with histologic diagnoses of the four tumor types (N=30 for each) and who meet safety criteria for nivolumab treatment are eligible. Prior treatment with checkpoint blockade is not allowed except for the melanoma cohort. In the phase 1 portion patients are treated by intra-patient dose escalation of virus (range, 104 - 108 PFU) by intratumoral injection every two weeks for 5 total doses followed by 12 patients dosed 8 times at the RP2D in combination with nivolumab. Phase 1 patients were divided into two groups based on presence of clinically accessible lesions amenable to direct injection or those with visceral/deep lesions requiring image guidance for injection. In the phase 2 portion patients will receive the RP2D for eight injections and nivolumab will be given starting with the second RP1 injection. For the phase 1 portion, a modified 3+3 dose escalation design is used to assess safety and in the phase 2 portion, statistical analysis will be performed using a two-stage three-outcome optimum design with objective responses determined by RECIST criteria. As of February 11, 2019, 27 patients have been enrolled. Clinical trial information: NCT03767348.

A phase I, dose-escalation study of ADG106, a fully human anti-CD137 agonistic antibody, in subjects with advanced solid tumors or relapsed/refractory non-Hodgkin lymphoma.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 3105-3105 ◽  
Author(s):  
Li Zhang ◽  
Hongyun Zhao ◽  
Yuxiang Ma ◽  
Xin Zheng ◽  
Ji Jiang ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Solid Tumors ◽  
Phase 1 ◽  
Objective Response ◽  
Systemic Exposure ◽  
Pharmacokinetic Analysis ◽  
Dose Escalation Study ◽  
Non Hodgkin Lymphoma ◽  
Expansion Cohort ◽  
Dose Levels

3105 Background: ADG106 is a fully human agonistic anti-CD137 monoclonal IgG4 antibody, targeting a unique epitope of CD137 with novel mechanism of actions for CD137 agonism, CD137 ligand antagonism and potent cross-linking via FcgRIIb. This phase 1 study was conducted to assess its safety, tolerability, pharmacokinetic (PK) profile, immunogenicity and preliminary efficacy. Methods: Eligible patients with age 18 to 75, ECOG ≤1, measurable lesion received intravenous infusion of ADG106 every 3 weeks for a maximum of 24 months. Accelerated titration was applied in 0.1mg/kg dose level and traditional Fibonacci 3+3 method was applied in 0.5, 1.5, 3.0, 5.0 and 10.0 mg/kg dose levels. A dose-expansion cohort will be started for dose levels that have been proved tolerable and with evidence of clinical or biological activity. Results: Data cutoff at Jan 17 2020, 15 patients [5 adenoid cystic carcinoma (ACC), 5 non-small cell lung cancer (NSCLC), 3 nasopharyngeal carcinoma, 1 malignant pleural mesothelioma and 1 follicular lymphoma] were enrolled and received treatment: 0.1mg/kg (n = 1), 0.5mg/kg (n = 3), 1.5mg/kg (n = 5), 3mg/kg (n = 3), and 5mg/kg (n = 3). Of these 15 patients, 6 with ongoing treatment, 9 discontinued (8 progression disease, 1 lack of clinical benefit). Medium treatment duration was 2 cycles (range 2-8). No dose limiting toxicities were observed. Seven (47%) patients experienced treatment-related AEs (TRAEs): rash (13%), pruritus (13%), nausea (7%), pyrexia (7%), hemoptysis (7%), mouth ulceration (7%), vomiting (7%), chest discomfort (7%), LDH increased (7%). All TRAEs were grade 1, no grade ≥3 occurred. One serious adverse event (anemia, not related) was observed. Pharmacokinetic analysis of ADG106 showed a half-life ranging from 5~10 days, with dose-dependent increase of systemic exposure. Treatment induced anti-drug antibodies were developed in 3 (20%) patients. No objective response was observed among the 14 evaluated patients. Disease control rate was 57% (8 stable disease), tumor shrinkage was observed in 3 (21%) patients (2 ACC, 1 NSCLC). Conclusions: ADG106 is safe and tolerable at doses up to 5 mg/kg in solid tumors and non-Hodgkin lymphoma. The dose expansion cohorts have started at selected doses. Clinical trial information: NCT03802955 .

scholarly journals Patient Age Associates With Tumor-Infiltrating Lymphocytes Density In Breast Cancer

2021 ◽  
Author(s):  
Koji Takada ◽  
Shinichiro Kashiwagi ◽  
Yuka Asano ◽  
Wataru Goto ◽  
Sae Ishihara ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Older Patients ◽  
Objective Response ◽  
Growth Factor Receptor ◽  
Tumor Infiltrating Lymphocytes ◽  
Complete Response ◽  
Therapeutic Effects ◽  
Significant Difference ◽  
Pre Treatment ◽  
Infiltrating Lymphocytes

Abstract Purpose: Lymphocytes surrounding the cancer participate in tumor-related immune responses, and are called tumor-infiltrating lymphocytes (TILs). Several recent reports suggest TILs to index the tumor-microenvironment (TME), and predict the therapeutic effect of chemotherapy. However, only few studies have studied the relationship between age and TILs. Aging reduces host immunity, and we predict that it may also affect TILs. Thus, we hypothesized that older breast cancer (BC) patients may have low TILs density than younger BC patients. Here, we retrospectively analyzed the differences in TILs by age and the therapeutic effects of pre-operative chemotherapy (POC) in BC patients aged less than 45 years and more than 60 years.Methods: POC was administered to 356 patients. We confirmed and compared TILs density and therapeutic effects in patients aged < 45 years (n=75) and those aged >61 years (n=116). TIL density was evaluated using pre-treatment needle biopsy specimens. Definition and evaluation of TILs was based on the International TILs Working Group 2014.Results: Based on subtype, younger patients showed significantly higher pathological complete response rates than older patients with hormone receptor (HR)+ human epidermal growth factor receptor 2 (HER2)+ and HER2-enriched BC. In HR+HER2+BC, the objective response rate was significantly high in younger than in older patients. Further, a significant difference was observed for overall survival between these patients with triple-negative BC.Conclusions: Our study suggests that younger BC patients possess significantly high TILs density than older patients. These differences may influence the therapeutic efficacy in highly immunogenic subtypes.

scholarly journals Safety, antitumor activity and biomarkers of sugemalimab in Chinese patients with advanced solid tumors or lymphomas: results from the first-in-human phase 1 trial

2022 ◽  
Author(s):  
Jifang Gong ◽  
Junning Cao ◽  
Qingyuan Zhang ◽  
Nong Xu ◽  
Yanqiu Zhao ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Solid Tumors ◽  
Phase 1 ◽  
Objective Response ◽  
Chinese Patients ◽  
Fixed Dose ◽  
Phase 1 Trial ◽  
Advanced Malignancies ◽  
Biomarker Analysis ◽  
Phase 1B

Abstract Background This first-in-human phase 1 trial is to evaluate the safety, pharmacokinetics, preliminary efficacy, and biomarkers of sugemalimab, a full-length, fully human anti-PD-L1 monoclonal antibody, in Chinese patients with advanced malignancies. Methods Eligible patients with unresectable advanced or metastatic solid tumors or lymphomas were enrolled in phase 1a to receive sugemalimab following a modified 3 + 3 design. The primary endpoints included safety, tolerability, and the recommended Phase 2 dose (RP2D). In phase 1b, patients with 7 selected types of tumor received sugemalimab at the RP2D alone (monotherapy cohorts) or in combination with standard-of-care (SOC) chemotherapy (combination cohorts). The primary endpoint of phase 1b was investigator-assessed objective response rate (ORR). Results As of 19 February 2020, 29 and 178 patients were treated in phase 1a and 1b, respectively. No dose-limiting toxicities were observed in phase 1a, and the RP2D of sugemalimab was determined as 1200 mg fixed dose once every 3 weeks. Sugemalimab-related adverse events (AEs) were mostly (75.9%) grade 1–2 in phase 1a. Antitumor activity was observed across dose levels with an ORR of 24.1%. In phase 1b, 15.9% and 40.4% of patients in the monotherapy and combination cohorts, respectively, reported grade 3–5 sugemalimab-related AEs. Promising efficacy was observed in all combination cohorts, with ORRs ranging from 47.6 to 75.0%. Exploratory biomarker analysis did not indicate significant differences in responses at different PD-L1 expression/tumor mutation burden levels. Conclusions Sugemalimab was well-tolerated and showed promising antitumor activity as monotherapy or in combination with SOC chemotherapy in advanced malignancies. This trial was registered with ClinicalTrials.gov on Oct 18, 2017, number NCT03312842.

Efficacy and safety of crizotinib in patients with advanced ROS1-rearranged non-small cell lung cancer (NSCLC).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 8032-8032 ◽  
Author(s):  
Sai-Hong Ignatius Ou ◽  
Yung-Jue Bang ◽  
D. Ross Camidge ◽  
Gregory J. Riely ◽  
Ravi Salgia ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Kinase Inhibitor ◽  
Phase 1 ◽  
Objective Response ◽  
Safety Data ◽  
Complete Response ◽  
Median Number ◽  
Efficacy And Safety ◽  
Alk Positive ◽  
Expansion Cohort

8032 Background: ROS1 receptor tyrosine kinase rearrangements define a subset of NSCLC sensitive to the small-molecule tyrosine kinase inhibitor crizotinib, approved multinationally for the treatment of advanced ALK-positive NSCLC. Updated efficacy and safety data are presented for crizotinib in patients with advanced ROS1-rearranged NSCLC. Methods: ROS1 status was determined by break-apart FISH assays, and patients were enrolled into an expansion cohort of an ongoing phase 1 crizotinib study (NCT00585195). Patients received crizotinib 250 mg BID. Responses were assessed using RECIST v1.0. The disease control rate (DCR; % stable disease [SD] + partial response [PR] + complete response [CR]) was evaluated at weeks 8 and 16. Results: At the data cut-off, 33 patients with ROS1-positive NSCLC had enrolled, and 31 had received crizotinib, with 25 evaluable for response. Median age was 51 years (range 31–72), 79% of patients were never-smokers and 97% had adenocarcinoma histology. The median number of prior treatments for advanced disease was 1 (range 0–7). The objective response rate (ORR) was 56% (95% CI: 24.4–65.1), with 2 CRs, 12 PRs and 8 SDs. 8-week and 16-week DCRs were 76% and 60%, respectively. Median PFS has not been reached, with ~60% of patients still in follow-up for PFS; 6-month PFS probability was 71% (95% CI: 45.6–86.0). Median treatment duration was 24 weeks (range 2.3–112), and 24 patients were on treatment at the data cut-off; 5 patients died (all disease-related). 91% of patients had treatment-related adverse events (AEs): most commonly visual impairment (82%), nausea (36%) and diarrhea (33%). Most AEs were grade 1 in severity. Peripheral edema and elevated transaminases were also reported, similar to the previous experience of crizotinib. There were no treatment-related serious AEs or treatment-related permanent discontinuations. Accrual of patients with ROS1-positive NSCLC is ongoing. Conclusions: As observed in ALK-positive NSCLC, crizotinib had dramatic antitumor activity with a high ORR (56%) in patients with ROS1-positive NSCLC and a generally tolerable and manageable AE profile. These findings indicate that crizotinib is an effective therapy for advanced ROS1-positive NSCLC. Clinical trial information: NCT00585195.

Phase 1 study of the liposomal formulation of eribulin (E7389-LF): Results from the advanced gastric cancer expansion cohort.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 4025-4025
Author(s):  
Kensei Yamaguchi ◽  
Satoru Iwasa ◽  
Motohiro Hirao ◽  
Takashi Oshima ◽  
Kazuaki Harada ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Febrile Neutropenia ◽  
Safety Profile ◽  
Phase 1 ◽  
Objective Response ◽  
Safety Data ◽  
Metastatic Breast ◽  
Prior Treatment ◽  
Phase 1 Study ◽  
Expansion Cohort

4025 Background: Eribulin has proven efficacy in previously treated metastatic breast cancer and liposarcoma. E7389-LF is a new formulation that uses liposomes to encapsulate eribulin, which is anticipated to improve eribulin concentration in tumor tissues. In the dose-expansion part of a phase 1 study of E7389-LF, the safety profile was acceptable and 2 patients (pts) out of 10 with gastric cancer (GC) had an objective response. Thus, the GC cohort was expanded for further evaluation. Here, we report efficacy and safety data from the phase 1 expansion cohort of pts with advanced GC who were treated with E7389-LF. Methods: Eligible pts were those with GC who had no alternative standard or effective therapy options after ≥2 prior chemotherapy regimens. Target total enrollment was 32 pts (10 pts in the initial GC cohort plus an additional 22 pts in the expanded cohort). E7389-LF 2.0 mg/m2 was administered intravenously once every 3 weeks. Tumor responses were assessed every 6 weeks (± 1 week) by RECIST v1.1. Results: At data cutoff (Oct 16, 2020), 34 pts with GC were enrolled (10 pts in the initial GC cohort; 24 pts in the expanded GC cohort) with a median of 5 prior therapies (range, 2–11). Previous immune checkpoint inhibitor (ICI) therapy was reported for 26 (76.5%) pts. All pts were evaluable for objective response rate (ORR) and progression-free survival (PFS), and 30 pts were evaluable for overall survival (OS). Among all pts with GC, the ORR was 17.6% (95% CI 6.8–34.5) and the disease control rate was 79.4% (95% CI 62.1–91.3). Median PFS was 3.7 months (95% CI 2.7–4.3) and median OS was 7.6 months (95% CI 6.7–15.4). The ORRs were 19.2% (95% CI 6.6–39.4) in ICI-pretreated pts and 12.5% (95% CI 0.3–52.7) in pts without prior ICI therapy. Median PFS was similar regardless of prior treatment with ICIs (3.7 months [95% CI 2.7–5.6] in ICI-pretreated pts vs 3.4 months [95% CI 1.0–4.3] in pts without prior ICI therapy); however, the PFS rate at 6 months in ICI-pretreated pts was higher vs the rate in pts without prior ICI therapy (35.9% [95% CI 17.2–55.1] vs 0%, respectively). Median OS was also longer in ICI-pretreated pts (evaluable pts, n = 23) vs pts without prior ICI therapy (evaluable pts, n = 7) (10.0 months [95% CI 6.7–not estimable] vs 6.7 months [95% CI 3.1–8.5], respectively). Common grade ≥3 adverse events included neutropenia (41.2%), leukopenia (29.4%), and anemia (26.5%). In cycle 1, there were no cases of febrile neutropenia among the 22 pts treated with prophylactic peg-GCSF; among pts who did not receive prophylactic peg-GCSF, 16.7% of pts had febrile neutropenia. Conclusions: E7389-LF had a manageable safety profile and encouraging activity in pts with heavily treated GC. In pts with GC, prior treatment with ICIs might enhance the potential efficacy of E7389-LF. These results support further development of E7389-LF for advanced GC. Clinical trial information: NCT03207672.

scholarly journals Patient Age Associates with Tumor-Infiltrating Lymphocytes Density in Breast Cancer

2021 ◽  
Author(s):  
Koji Takada ◽  
Shinichiro Kashiwagi ◽  
Yuka Asano ◽  
Wataru Goto ◽  
Sae Ishihara ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Older Patients ◽  
Objective Response ◽  
Growth Factor Receptor ◽  
Tumor Infiltrating Lymphocytes ◽  
Complete Response ◽  
Therapeutic Effects ◽  
Significant Difference ◽  
Pre Treatment ◽  
Infiltrating Lymphocytes

Abstract Purpose: Lymphocytes surrounding the cancer participate in tumor-related immune responses, and are called tumor-infiltrating lymphocytes (TILs). Several recent reports suggest TILs to index the tumor-microenvironment (TME), and predict the therapeutic effect of chemotherapy. However, only few studies have studied the relationship between age and TILs. Aging reduces host immunity, and we predict that it may also affect TILs. Thus, we hypothesized that older breast cancer (BC) patients may have low TILs density than younger BC patients. Here, we retrospectively analyzed the differences in TILs by age and the therapeutic effects of pre-operative chemotherapy (POC) in BC patients aged less than 45 years and more than 60 years.Methods: POC was administered to 356 patients. We confirmed and compared TILs density and therapeutic effects in patients aged < 45 years (n=75) and those aged >61 years (n=116). TIL density was evaluated using pre-treatment needle biopsy specimens. Definition and evaluation of TILs was based on the International TILs Working Group 2014.Results: Based on subtype, younger patients showed significantly higher pathological complete response rates than older patients with hormone receptor (HR)+ human epidermal growth factor receptor 2 (HER2)+ and HER2-enriched BC. In HR+HER2+BC, the objective response rate was significantly high in younger than in older patients. Further, a significant difference was observed for overall survival between these patients with triple-negative BC.Conclusions: Our study suggests that younger BC patients possess significantly high TILs density than older patients. These differences may influence the therapeutic efficacy in highly immunogenic subtypes.

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