Results of a phase Ib trial evaluating the safety and clinical activity of sapanisertib (TAK 228) in combination with serabelisib (TAK 117) and paclitaxel in patients with advanced ovarian, endometrial, or breast cancer.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 3604-3604
Author(s):  
Casey B. Williams ◽  
Kirstin Anne Williams ◽  
Amy K. Krie ◽  
Pradip De ◽  
Nandini Dey ◽  
...  
Keyword(s):  
Clinical Results ◽  
Clinical Activity ◽  
Open Label ◽  
Effective Treatment Option ◽  
Taxane Resistance ◽  
Phase 2 Study ◽  
Heavily Pretreated ◽  
Pretreated Patients ◽  
Grade 3 ◽  
Dose Reductions

3604 Background: The link between taxane resistance and activation of PI3K/AKT/mTOR signaling suggests that by inhibiting this pathway in combination with anti-microtubule agents like paclitaxel may improve treatment outcomes in many malignancies. To investigate this further we combined the TORC 1/2 inhibitor sapanisertib (TAK-228), the PI3Kα isoform inhibitor serabelisib (TAK-117), and paclitaxel in a phase I trial to determine the safety, efficacy, and RP2D. Methods: Open label, cohort study using a traditional 3+3 dose escalation design with a maximum of 5 dosing cohorts. A dose expansion of cohort 4, the recommended RP2D, is planned for February 2020. Results: Enrollment to the DLT evaluation has been completed and the clinical results are summarized in Table. Sixteen patients have been enrolled; a majority were heavily pretreated and resistant to paclitaxel. Overall, the combination was safe and tolerable. One DLT occurred due to renal dysfunction in cohort 5. 360 adverse events have been reported, but only 28 (8%) grade 3 or 4 events. The most common events were leukopenia and non-febrile neutropenia. Two patients required dose reductions as a result of pneumonitis. The ORR is currently 46% in 13 evaluable patients. CBR is 69% and PFS is currently at 10 months. Two patients achieved a CR and three patients remain on treatment. Conclusions: The combination proved to be well tolerated in the doses and schedules used in cohorts 1-4 and exhibited very promising clinical activity in heavily pretreated patients. This regimen could prove to be a highly effective treatment option and a phase 2 study is warranted at the RP2D. Clinical trial information: NCT03154294 . [Table: see text]

Final results of phase 1 evaluation of the safety and clinical activity of sapanisertib in combination with serabelisib and paclitaxel in patients with advanced ovarian, endometrial, or breast cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 5569-5569
Author(s):  
David Starks ◽  
Luis Alexander Rojas-Espaillat ◽  
Nandini Dey ◽  
Pradip De ◽  
Brian Leyland-Jones ◽  
...  
Keyword(s):  
Clinical Benefit ◽  
Phase 1 ◽  
Endometrial Adenocarcinoma ◽  
Mtor Pathway ◽  
Clinical Activity ◽  
Open Label ◽  
Serious Adverse Events ◽  
Positive Effects ◽  
Taxane Resistance ◽  
Heavily Pretreated

5569 Background: Evidence suggests that activation of the PI3K/AKT/mTOR pathway by paclitaxel may play a role in the development of taxane resistance. Conversely, PI3K inhibitors have been shown to sensitize tumors to the effects of paclitaxel. Therefore, the link between taxane resistance and activation of the PI3K/AKT/mTOR signaling pathway suggests inhibition of this pathway in combination with antimitotic drugs like paclitaxel may improve treatment outcomes in many malignancies. To further investigate this hypothesis we combined the TORC 1/2 inhibitor sapanisertib (TAK-228), the PI3Kα isoform inhibitor serabelisib (TAK-117), and paclitaxel in a phase I trial of heavily pretreated patients to determine the safety, efficacy, and RP2D. Methods: This is an open label, cohort study of sapanisertib (TAK-228) and serabelisib (TAK-117) given on days 2-4, 9-11, 16-18, and 23-25 with paclitaxel on days 1, 8, and 15 of a 28-day cycle. A traditional 3+3 dose escalation design with a maximum of 5 dosing cohorts was used. All 5 cohorts plus an expansion cohort are presented. Results: Enrollment has been completed and the overall results are summarized. Nineteen patients were enrolled; the majority were heavily pretreated with the average number of prior regimens exceeding 4. Based upon ITT, the ORR is 37%. The ORR is 47% in patients that completed at least 3 cycles. The clinical benefit rate is 73% and the PFS currently stands at approximately 11 months. Two patients with endometrioid endometrial adenocarcinoma achieved a complete response. All patients received comprehensive genomic profiling and 7 patients received prior mTOR inhibitor. Overall, the combination was well tolerated, except by patients in cohort 5. One DLT occurred in the last patient enrolled. The most common non-laboratory AEs were nausea (6%), fatigue (5%), and mucositis (5%). There were 45 (9%) grade 3 or 4 events, and the most common were decreased WBC and non-febrile neutropenia. Hyperglycemia was common in patients with a history of diabetes mellitus. Conclusions: Overall, the combination of sapanisertib, serabelisib, and paclitaxel was safe and efficacious throughout the first 4 cohorts. There were few serious adverse events, and most side effects were managed with routine supportive care interventions. Preliminary clinical results appear very promising, especially for patients with PI3K/AKT/mTOR pathway mutations. The positive effects of the combination were routinely seen in the lowest dosing cohorts and clinical benefit was even seen in patients that had previously failed everolimus or temsirolimus. All patients were either resistant or refractory to paclitaxel at time of enrollment, so further exploration of this combination to elucidate the mechanism of benefit is warranted. Clinical trial information: NCT03154294.

Safety and Efficacy of Bortezomib (Velcade) for the Treatment of Relapsed Classical Hodgkin’s Disease.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2638-2638 ◽  
Author(s):  
Anas Younes ◽  
Barbara Pro ◽  
Jorge Romaguera ◽  
Nam Dang
Keyword(s):  
Platelet Count ◽  
Treatment Response ◽  
Cell Lines ◽  
Single Agent ◽  
Prior Treatment ◽  
Clinical Activity ◽  
Treatment Regimens ◽  
Heavily Pretreated ◽  
Pretreated Patients ◽  
Grade 3

Abstract The proteasome inhibitor bortezomib has demonstrated clinical activity in patients with multiple myeloma and different types of non-Hodgkin’s lymphoma. Its activity in patients with Hodgkin’s disease (HD) is unknown. We have recently reported that bortezomib had a significant activity against HD-derived cell lines in vitro (Zheng et al, Clin Cancer Res 2004), In four HD-derived cell lines, bortezomib induced cell cycle arrest and apoptosis in a dose and time dependent manner, irrespective of IkB gene mutations. Furthermore, bortezomib enhanced the activity of chemotherapy and TRAIL in these cell lines. Based on these encouraging preclinical results, we initiated a pilot study of single agent bortezomib in patients with relapsed classical HD. Eligibility: (1) relapsed classical HD with a measurable disease (2) At least 2 prior treatment regimens; (3) Patients with prior autologous stem cell transplant (ASCT) are eligible (4) platelet counts > 50,000/uL and ANC counts of > 1,500/uL (5) no HIV infection, or CNS involvement with HD, (6) bilirubin < 2mg/dL and creatinine < 2.5 mg/dL. Patients were treated with 1.3 mg/m2 bortezomib intravenously on days 1, 4, 8, 11 of 21-day cycles in an outpatient setting. Treatment was delayed if the Platelet counts on the day of therapy was < 30,000/mm3. After 3 cycles of bortezomib therapy patients were evaluated for treatment response. If there was no evidence of disease progression after 3 cycles of therapy, patients were allowed to receive a maximum of 6 cycles. To date, 11 patients are enrolled (6 men and 5 women), with a median age of 28 years (range: 21 to 68 years). All patients were heavily pretreated, with a median number of 5 prior treatment regimens (range 2 to 7 regimens), and all patients have previously failed ASCT. The median pretreatment platelet count was 126, 000/uL (range 66,000 – 339,000/uL). All patients received at least one dose of bortezomib and are evaluable for treatment toxicity. Treatment was reasonably well tolerated with the majority of toxic effects were of grade 1 and 2. Two patients had grade 3 dyspnea and one patient had grade 3 neutropenic fever. Progressive thrombocytopenia was the most common hematologic toxicity, which frequently caused delays in therapy. Nadir platelet count below 30,000/uL was observed in 3/11 patients during the first cycle, in 4/10 during the second cycle, and in 4/6 during the third cycle. Nadir ANC below 1000/uL was observed in 1/11 pts during cycle 1, in 2/10 during cycle 2, and in 1/6 during cycle 3. Eight patients completed the planned 3 cycles and are evaluable for treatment response. One patient achieved a partial remission and one had a minimal response. Our preliminary data demonstrate encouraging clinical activity of bortezomib in this heavily pretreated patients with classical HD, and warrants studying bortezomib in less heavily pretreated patients either as a single agent or in combination with chemotherapy.

A randomized phase II study (VEG108838) of lapatanib plus pazopanib (L+P) versus lapatanib (L) in patients with ErbB2+ inflammatory breast cancer (IBC).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 531-531 ◽  
Author(s):  
Massimo Cristofanilli ◽  
Stephen R. D. Johnston ◽  
Alexey Manikhas ◽  
Henry Leonidas Gomez ◽  
Oleg Gladkov ◽  
...  
Keyword(s):  
Randomized Study ◽  
Single Agent ◽  
Clinical Activity ◽  
Study Cohort ◽  
Open Label ◽  
Double Blind ◽  
Meaningful Improvement ◽  
Grade 3 ◽  
To Receive ◽  
Dose Reductions

531 Background: ErbB2 amplification is frequently reported in IBC and there is evidence of positive association between ErbB2 and VEGF expression. We evaluated the combination of anti ErbB2 and VEGF therapy in ErbB2+ IBC. Methods: We conducted a multicenter, randomized clinical trial for patients (pts) with relapsed ErbB2+ IBC. Cohort 1: Pts stratified (prior trastuzumab; cutaneous disease only vs systemic) and randomized 1:1 to receive L 1500 mg + placebo or L 1500 mg + P 800 mg, QD. Due to high incidence of Grade 3/4 diarrhea in pts treated with L 1500 mg+ P 800 mg in another study, Cohort 1 was closed after 76 pts randomized. Cohort 2 (87 pts ): Pts were stratified (prior trastuzumab) and randomized 5:5:2 to receive L 1500 mg + placebo or L 1000 mg + P 400 mg (double-blind) or P 800 mg (open-label), respectively, QD. Treatment continued until PD, unacceptable toxicity or death. Primary endpoint was ORR. Secondary endpoints included PFS, OS, and safety. Results: Cohort 1: 76 pts were randomized and treated: L, n=38; L+P, n=38. ORR was 29% for the L arm, and 45% for the L+P arm. Median PFS was 16.1 and 14.3 wks, respectively, for the L and L+P arms. The most frequent Grade ≥3 AEs were diarrhea (0% vs 18%) vomiting (0% vs 8%), ALT increased (0% vs 8%), neutropenia (3% vs 13%), and bilirubin increased (0% vs 5%). Dose reductions due to AE were 3% and 21% and dose interruptions due to AE were 11% and 55% in the L and L+P arms, respectively. Cohort 2: 88 pts were randomized (87 treated): L, n=36; P, n=14; L+P, n=38. The ORR was 47%, 31%, and 58% for the L, P, and L+P arms, respectively. Median PFS was 16.0, 11.4, and 16.0 wks for the L, P, and L+P arms, respectively. The most frequent Grade ≥3 AEs were ALT increased (0%, 0%, 21%), AST increased (0%, 0%, 18%), diarrhea (3%, 8%, 8%), and fatigue (3%, 8%, 8%). Dose reductions due to AE occurred in 0%, 0%, and 13% of pts and dose interruptions due to AE occurred in 22%, 23%, and 39% of pts in the L, P, and L+P arms, respectively. Conclusions: This prospective, randomized study confirmed the clinical activity of lapatinib single agent in metastatic ErbB2+ IBC. Furthermore, we demonstrated increased toxicity associated with the combination without a clinically meaningful improvement in efficacy.

Everolimus for Relapsed/Refractory Classical Hodgkin Lymphoma: Multicenter, Open-Label, Single-Arm, Phase 2 Study.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2740-2740 ◽  
Author(s):  
Patrick B. Johnston ◽  
Lauren Pinter-Brown ◽  
Jaqueline Rogerio ◽  
Ghulam Warsi ◽  
Quincy Chau ◽  
...  
Keyword(s):  
Computed Tomography ◽  
Disease Progression ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Phase 2 ◽  
Open Label ◽  
Phase 2 Study ◽  
Heavily Pretreated ◽  
Equity Ownership ◽  
Grade 3

Abstract Abstract 2740 Background: Historically, treatment options for the approximately 30% of patients with Hodgkin lymphoma (HL) who have primary refractory disease or relapse after experiencing initial response have been limited to high-dose chemotherapy with autologous hematopoietic stem cell transplant (AHSCT). Development of novel therapeutic options is needed to improve outcomes in patients whose disease is refractory to or relapses after initial chemotherapy or subsequent high-dose chemotherapy with AHSCT. The oral mammalian target of rapamycin inhibitor everolimus showed promising efficacy and acceptable toxicity in 19 patients with heavily pretreated HL enrolled in a phase 2 study of everolimus monotherapy for relapsed, rare lymphomas (Johnston et al. Am J Hematol 2010;85:320-4). To confirm the efficacy and safety of everolimus monotherapy in patients with relapsed/refractory classical HL, we conducted a multicenter, open-label, 2-step, phase 2 study. Methods: Adults with classical HL that progressed after high-dose chemotherapy with AHSCT or a gemcitabine-, vinorelbine-, or vinblastine-containing regimen received everolimus 10 mg/day until disease progression or unacceptable toxicity. Response was assessed every 12 weeks via computed tomography with contrast or integrated positron emission tomography/computed tomography with contrast. The primary study endpoint was the overall response rate (ORR) evaluated according to the modified response criteria for malignant lymphoma (Cheson et al. J Clin Oncol 2007;25:579-86). Secondary endpoints included the disease control rate (DCR), duration of overall response, duration of disease control, progression-free survival (PFS), and safety. Results: A total of 57 patients were enrolled in this study; 57.9% were women, the median age was 32.0 years, 57.9% were pretreated with AHSCT, and 100% were pretreated with gemcitabine, vinorelbine, or vinblastine. Overall, 66.7% of patients experienced disease progression during previous therapies or discontinued previous treatment due to progression. At the time of analysis, 48 patients discontinued study treatment, most commonly due to disease progression (n = 25). The ORR and DCR were 42.1% and 77.2%, respectively (Table). The median time to response was 57 days. Median PFS was 9.0 months. Adverse events experienced by >25% of patients were fatigue (56.1%), thrombocytopenia (47.4%), cough (38.6%), rash (38.6%), pyrexia (31.6%), anemia (29.8%), dyspnea (28.1%), back pain (26.3%), and diarrhea (26.3%). Grade 3/4 adverse events were observed in 33 patients (57.9%); the most common were thrombocytopenia (21.1%) and anemia (12.3%). Stomatitis was experienced by 14 patients (24.6%) and was of grade 3 severity in 2 patients (3.5%). Pneumonitis was observed in 6 patients (10.5%) and was of grade 1 severity in 2 patients (3.5%) and grade 2 severity in 4 patients (7.0%). Conclusions: In this phase 2 study, everolimus monotherapy demonstrated favorable efficacy and a short time to response in patients with heavily pretreated, relapsed/refractory classical HL. The overall safety profile was consistent with that previously observed for everolimus in patients with HL and other cancers. The results of this study confirm previous results and support the further evaluation of everolimus in patients with classical HL. Disclosures: Johnston: Novartis: Consultancy. Off Label Use: Everolimus is an mTOR inhibitor indicated in the US for the treatment of postmenopausal women with advanced hormone receptor-positive, HER2-negative breast cancer in combination with letrozole after failure of letrozole or anastrozole; adults with progressive pancreatic neuroendocrine tumors that are unresectable, locally advanced, or metastatic; adults with advanced renal cell carcinoma after failure of treatment with sunitinib or sorafenib; adults with renal angiomyolipoma and tuberous sclerosis complex not requiring immediate surgery; and adults and children aged 3 years or greater with subependymal giant cell astrocytoma associated with tuberous sclerosis complex who require therapeutic intervention but are not candidates for curative surgical resection. Pinter-Brown:Millennium: Consultancy. Rogerio:Novartis: Employment; Novartis: Equity Ownership. Warsi:Novartis: Employment; Novartis: Equity Ownership. Chau:Novartis: Employment. Ramchandren:Seattle Genetics: Honoraria.

Sorafenib-Regorafenib Sequential Therapy in Advanced Hepatocellular Carcinoma: A Single-Institute Experience

2017 ◽  
Vol 35 (6) ◽  
pp. 611-617 ◽  
Author(s):  
Kazuomi Ueshima ◽  
Naoshi Nishida ◽  
Masatoshi Kudo
Keyword(s):  
Hepatocellular Carcinoma ◽  
Objective Response ◽  
Progression Free Survival ◽  
Sequential Therapy ◽  
Advanced Hepatocellular Carcinoma ◽  
Open Label ◽  
Effective Treatment Option ◽  
Sorafenib Treatment ◽  
Advanced Hcc ◽  
Grade 3

Objectives: Previously, no therapeutic agent has been known to improve the overall survival compared with placebo in patients with hepatocellular carcinoma (HCC), who have progressed after sorafenib. In this patient population, regorafenib was first demonstrated to confer a survival benefit in the RESORCE trial, and subsequently it was approved as a second-line treatment for patients with advanced HCC. An open-label expanded access program (EAP) of regorafenib was implemented for compassionate use. We investigated the efficacy and safety of regorafenib based on our experience of the RESORCE trial and the EAP. Methods: Data from 5 patients from the RESORCE trial and 6 from the EAP were analyzed retrospectively. All patients had tolerated prior sorafenib and were progressing during sorafenib treatment. Results: The median progression-free survival was 9.2 months (95% CI 2.3-16.1). One patient achieved a partial response and 7 achieved stable disease. The objective response rate was 9.1%, and the disease control rate was 72.7%. No treatment-associated mortalities were observed. Grade 3 hypophosphatemia was observed in 2 patients, grade 2 anorexia was observed in 5 patients, and grade 3 neutropenia was observed in 2 patients. Grade 2 and grade 3 thrombocytopenia were observed in 2 and 3 patients, respectively. All treatment-related adverse events were improved by reduction or interruption of regorafenib. Five patients showed decreased serum albumin levels. Conclusion: Sorafenib and regorafenib sequential therapy presents a safe and effective treatment option for patients with advanced HCC.

Phase II Study of Temsirolimus (CCI-779), a Novel Inhibitor of mTOR, in Heavily Pretreated Patients With Locally Advanced or Metastatic Breast Cancer

2005 ◽  
Vol 23 (23) ◽  
pp. 5314-5322 ◽  
Author(s):  
Stephen Chan ◽  
Max E. Scheulen ◽  
Stephen Johnston ◽  
Klaus Mross ◽  
Fatima Cardoso ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Adverse Events ◽  
Dose Level ◽  
Locally Advanced ◽  
Metastatic Breast ◽  
Heavily Pretreated ◽  
Pretreated Patients ◽  
Grade 3 ◽  
Time To Tumor Progression

Purpose In this study, two doses of temsirolimus (CCI-779), a novel inhibitor of the mammalian target of rapamycin, were evaluated for efficacy, safety, and pharmacokinetics in patients with locally advanced or metastatic breast cancer who had been heavily pretreated. Patients and Methods Patients (n = 109) were randomly assigned to receive 75 or 250 mg of temsirolimus weekly as a 30-minute intravenous infusion. Patients were evaluated for tumor response, time to tumor progression, adverse events, and pharmacokinetics of temsirolimus. Results Temsirolimus produced an objective response rate of 9.2% (10 partial responses) in the intent-to-treat population. Median time to tumor progression was 12.0 weeks. Efficacy was similar for both dose levels but toxicity was more common with the higher dose level, especially grade 3 or 4 depression (10% of patients at the 250-mg dose level, 0% at the 75-mg dose level). The most common temsirolimus-related adverse events of all grades were mucositis (70%), maculopapular rash (51%), and nausea (43%). The most common, clinically important grade 3 or 4 adverse events were mucositis (9%), leukopenia (7%), hyperglycemia (7%), somnolence (6%), thrombocytopenia (5%), and depression (5%). Conclusion In heavily pretreated patients with locally advanced or metastatic breast cancer, 75 and 250 mg temsirolimus showed antitumor activity and 75 mg temsirolimus showed a generally tolerable safety profile.

Clinical Response in Heavily Pretreated Mycosis Fungoides with Pembrolizumab: A Case Report

2021 ◽  
pp. 1-3
Author(s):  
Ginevra Lolli ◽  
Beatrice Casadei ◽  
Lisa Argnani ◽  
Alessandro Pileri ◽  
Cinzia Pellegrini ◽  
...  
Keyword(s):  
Mycosis Fungoides ◽  
Assessment Tool ◽  
Therapeutic Option ◽  
Rapid Responses ◽  
Duration Of Response ◽  
Heavily Pretreated ◽  
Stage Ia ◽  
Pretreated Patients ◽  
Grade 3 ◽  
The Moment

Mycosis fungoides (MF) is a disease almost impossible to cure. In the context of heavily pretreated patients, the anti-programmed cell death protein 1 (anti-PD-1) pembrolizumab is a valid therapeutic option. The alteration of the PD-1-PD ligand 1 (PD-L1) axis is often present in MF, and this aspect explains the feasibility of this therapy. We report the case of a 60-year-old woman diagnosed with MF in 2003, Olsen stage IA (T1M0NXBO). Since the moment of the diagnosis, she received 10 lines of therapy, with a short duration of response after each one of them. In April 2020, our patient started pembrolizumab 2 mg/kg every 3 weeks, and she achieved a partial response after the 4th cycle, consistent with the modified severity assessment tool (mSWAT) 1, which she is still maintaining after 10 cycles. No grade ≥3 adverse events were recorded. We conclude that pembrolizumab can induce extremely rapid responses in MF, with very low toxicity.

scholarly journals Pomalidomide-Dexamethasone in the Management of Heavily Pretreated Multiple Myeloma

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 1-1
Author(s):  
Claudio Cerchione ◽  
Lucio Catalano ◽  
Davide Nappi ◽  
Anna Emanuele Pareto ◽  
Gerardo Musuraca ◽  
...  
Keyword(s):  
Oral Administration ◽  
Oral Treatment ◽  
Novel Agents ◽  
Hematologic Toxicity ◽  
Salvage Regimen ◽  
Good Compliance ◽  
Impressive Result ◽  
Heavily Pretreated ◽  
Pretreated Patients ◽  
Grade 3

Background Pomalidomide is a new generation IMID, with a very good compliance, thanks to oral administration, which can be used also in heavily pretreated patients, in a domestic setting. Aims In this retrospective observational trial, It has been evaluated efficacy and tolerance of pomalidomide plus dexamethasone (PD) as salvage regimen in heavily pretreated patients with relapsed and refractory MM (rrMM), whose prognosis is particularly severe. Methods 57 patients (31 M/26 F), with rrMM, median age at diagnosis 69 years (r. 52-86), and median age at start of treatment 76 years (r.56-90) treated with several lines of treatments (median 7, r. 2-11), every refractory to all the drugs previously received (also Bortezomib, Thalidomide and Lenalidomide), received Pomalidomide-Dexamethasone (Pomalidomide 4 mg for 21 days, Dexamethasone 40 mg days 1,8,15,22, pegfilgrastim day +8) every 28 days, until progression. ISS was equally distributed, and cytogenetic at relapse was evaluable in 14 patients. All the patients had previously been treated with schedule containing bortezomib and IMIDs. 63% (36/57) had undergone at least to a single ASCT. All patients were relapsed and refractory to last therapies received before PD. Results Pomalidomide was well tolerated, with grade 3-4 transfusion-dependent anemia in 58% (33/57) of patients, 44% (23/57) grade 3-4 neutropenia (pegfilgrastim in primary prophylaxis was given, no hospitalization was required, no septic shocks were observed), 40% (23/57) grade 3-4 thrombocytopenia without hemorrhagic events and transfusion-dependence. No severe extra-hematologic toxicity was observed. According to IMWG, ORR1 (≥PR) was 47.3% (27/57: 5 CR, 11 VGPR, 7 PR, 4 MR), but, considering that we are evaluating a cohort of heavily pretreated patients, with poor prognosis, another parameter should be considered, ORR2 (≥SD), considering stable disease as a successful result in progressive MM. ORR2 was 77.1% (17 SD). These can be considered as impressive result in this subset of patients. Oral treatment gives a really good compliance, in frail and unfit patients, and response, when present, is always really fast (median time to response: 2 months (r.1-6)), median OS from diagnosis was 94 months (range 21-234), median OS from start of pomalidomide was 9 months (range 1-25). Nine patients have surprisingly achieved a notable response (3 VGPR, 4 PR, 2 MR) after failure of novel agents (i.e. Carfilzomib, Daratumumab and Pomalidomide). Conclusions Pomalidomide-dexamethasone has shown significant efficacy and a very good compliance, thanks to oral administration, in a particularly severe setting of heavily pretreated patients, relapsed and refractory to all available therapeutic resources, also after failure of novel agents. Disclosures Lucchesi: Novartis: Honoraria; Pfizer: Honoraria; Incyte: Honoraria.

CTIM-32. IMMUNE CHECKPOINT INHIBITOR NIVOLUMAB IN PEOPLE WITH RECURRENT SELECT RARE CNS CANCERS: RESULTS OF INTERIM ANALYSIS IN A HEAVILY PRETREATED COHORT

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi57-vi58
Author(s):  
Marta Penas-Prado ◽  
Ying Yuan ◽  
Kathleen Wall ◽  
Elizabeth Vera ◽  
Ukeme Ikiddeh-Barnes ◽  
...  
Keyword(s):  
Safety Profile ◽  
Interim Analysis ◽  
Cns Tumors ◽  
Myxopapillary Ependymoma ◽  
Investigational Drugs ◽  
Heavily Pretreated ◽  
Pretreated Patients ◽  
Grade 3 ◽  
Total Accrual ◽  
Immune Profiling

Abstract INTRODUCTION Standard and experimental therapies for patients with rare CNS tumors are scarce. Nivolumab (PD-1 inhibitor) is approved for several non-CNS cancers. This ongoing Phase II trial (NCT03173950) will determine the efficacy of nivolumab in adults with recurrence/progression of one of 11 selected rare primary CNS tumors. Efficacy is measured by Disease Control Rate (DCR; confirmed CR/PR or durable SD for ≥ 6 months) in 2 cohorts: heavily and non-heavily pretreated patients (heavily pretreated: ≥ 3 prior therapies; non-heavily pretreated: ≤ 2). We report efficacy and safety results of a preplanned interim analysis in the heavily pretreated cohort. METHODS Eligibility includes recurrence/progression of an eligible tumor; age ≥ 18 years; tumor tissue available for histopathology, molecular and immune profiling; KPS ≥ 70; and no steroids at study entry. A total of 150 evaluable patients will be enrolled (75 to each cohort). Prior therapies include radiation and/or standard or investigational drugs. Nivolumab treatment is 240 mg IV every 2 weeks (4 doses); then 480 mg every 4 weeks (14 additional doses). Interim analysis was planned when sample size reached 32 in each cohort. RESULTS As of March 10, 2021, DCR exceeded the minimum required for interim analysis in the heavily pretreated cohort. Among 30 patients, 4 achieved SD &gt; 6 months (medulloblastoma, anaplastic ependymoma, myxopapillary ependymoma, metastatic atypical meningioma). Safety profile (related AEs): grade 3 = 7; grade 4 = 1. Most frequent grade 3-5 AEs regardless of attribution: tumor progression (6); anemia, hydrocephalus, lymphopenia (3 each); cerebral edema, headache (2 each). CONCLUSION DCR exceeded the “go” boundary (i.e., &gt; 2) in the heavily pretreated cohort. Nivolumab showed safety profile consistent with other studies. This cohort will continue to stage 2 and complete total accrual of 75 patients. The trial is currently being expanded to 10 additional sites across the BTTC/NCI-CONNECT consortium.

Sign in / Sign up

Export Citation Format

Share Document