scholarly journals Abiraterone in patients with recurrent epithelial ovarian cancer: principal results of the phase II Cancer of the Ovary Abiraterone (CORAL) trial (CRUK – A16037)

2020 ◽  
Vol 12 ◽  
pp. 175883592097535
Author(s):  
Susana Banerjee ◽  
Holly Tovey ◽  
Rebecca Bowen ◽  
Elizabeth Folkerd ◽  
Lucy Kilburn ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Phase Ii ◽  
Clinical Benefit ◽  
Objective Response ◽  
Evaluation Criteria ◽  
Clinical Activity ◽  
Low Grade ◽  
Open Label ◽  
Grade 3

Background: Recurrent epithelial ovarian cancer (EOC) remains difficult to treat, with an urgent need for more therapy options. Androgens bind to the androgen receptor (AR), commonly expressed in EOC. CYP17 inhibitor abiraterone irreversibly inhibits androgen biosynthesis. The Cancer of the Ovary Abiraterone (CORAL) trial was designed to evaluate the clinical activity of abiraterone in EOC. Patients & Methods: CORAL was a multi-centre, open-label, non-randomised, 2-stage phase II clinical trial. Eligible patients had progression within 12 months of last systemic therapy and no prior hormonal anti-cancer agents. Patients received abiraterone 1000 mg daily plus 5 mg prednisone until progression. The primary endpoint was objective response rate (ORR) according to combined Response Evaluation Criteria in Solid Tumours/Gynaecological Cancer Intergroup (RECIST/GCIG) criteria at 12 weeks. Secondary endpoints included clinical benefit rate (CBR) at 12 weeks. Results: A total of 42 patients were recruited; median age 65 (range 34–85) years; 37 (88.1%) had high-grade serous tumours; 20 (48%) had at least three prior lines of therapy; 29/40 (72.5%) were AR+. In stage 1, 1/26 response was observed (in an AR+, low-grade serous EOC); response lasted 47 weeks. Overall, 12 week ORR was 1/42 (2%), CBR was 11/42 (26%) (8/29 (28%) in AR+ patients). Disease control was ⩾6 months for 4/29 (14%). One patient (AR+, low-grade serous) had a RECIST response at 82 weeks. Four (10%) had grade ⩾3 hypokalaemia; 11 (26%) had dose delays. Conclusions: CORAL represents the first trial of an AR targeted agent in ovarian cancer. While responses were rare, a subset of patients achieved sustained clinical benefit. Targeting AR in EOC including low-grade serous cancer warrants further investigation. Trial registration: CORAL is registered on the ISRCTN registry: ISRCTN63407050; http://www.isrctn.com/ISRCTN63407050

A phase Ib/II, multicenter, open-label study of DSP-7888 dosing emulsion in combination with immune checkpoint inhibitors (CPI) nivolumab or pembrolizumab in adult patients (pts) with advanced solid tumors, including platinum-resistant ovarian cancer (PROC).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. TPS6099-TPS6099
Author(s):  
Makoto Origuchi ◽  
Chris Korth ◽  
Zhonggai Li ◽  
Edgar E. Braendle
Keyword(s):  
Ovarian Cancer ◽  
Solid Tumors ◽  
Phase Ii ◽  
Metastatic Cancer ◽  
Objective Response ◽  
Clinical Activity ◽  
Induction Phase ◽  
Advanced Solid Tumors ◽  
Open Label ◽  
Phase Ib

TPS6099 Background: DSP-7888 is a therapeutic cancer vaccine composed of two synthetic peptides derived from Wilms’ tumor 1 (WT1) to promote both cytotoxic and helper T-lymphocyte-mediated immune responses against WT1-expressing tumors. WT1 is overexpressed in various solid tumors, including ovarian cancer. Combining cancer vaccines like DSP-7888 with a CPI may reduce resistance to immunomodulators and improve clinical benefit. A phase Ib/II study is being conducted to evaluate DSP-7888 in combination with a CPI in pts with advanced solid tumors, including PROC (NCT03311334). Methods: This phase Ib/II, open-label, multicenter, two-part dose-search/dose-expansion study investigates DSP-7888 + nivolumab or pembrolizumab in pts with advanced solid tumors (phase Ib), including PROC (phase II). The phase Ib primary objectives are safety, tolerability, and identification of the recommended phase II dose (RP2D). The phase II primary objective is evaluation of objective response rate (ORR); secondary objectives are clinical activity, safety, and tolerability. Pts aged ≥18 years with unresectable, metastatic cancer approved for treatment with nivolumab (phase Ib, Arm 1, n=6–12, 7 enrolled) or pembrolizumab (phase Ib, Arm 2, n=6–12, 6 enrolled), or with PROC (phase II) are eligible. Phase II will enroll ~40 pts into two groups based on programmed death-ligand 1 status (combined positive score of ≥10 [Group 1] or <10 [Group 2]). Clinical activity will be assessed continuously using Bayesian analysis and actual enrollment may increase by ~20 pts/group based on this analysis. Pts in phase II will receive DSP-7888 intradermally (RP2D from phase Ib) once a week (wk) for 6 wks in the induction phase then every 3 wks in the maintenance phase. Beginning Day 1, pembrolizumab will be administered intravenously every 3 wks. In phase II, objective disease will be assessed every 6 wks for 24 wks, then every 12 wks until progression. Endpoints include ORR (per RECIST v1.1) (primary), duration of response, disease control rate (DCR), progression-free survival (PFS), 6-month PFS rate (per RECIST v1.1), and overall survival, immune (i)ORR, iDCR, and iPFS (per iRECIST) (secondary). Exploratory endpoints include blood and tumor tissue biomarkers. Safety and tolerability, assessed by adverse events, will be evaluated throughout the duration of the study and follow-up. This study is currently recruiting patients. Clinical trial information: NCT03311334.

EFFORT: EFFicacy Of adavosertib in parp ResisTance: A randomized two-arm non-comparative phase II study of adavosertib with or without olaparib in women with PARP-resistant ovarian cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 5505-5505
Author(s):  
Shannon Neville Westin ◽  
Robert L. Coleman ◽  
Bryan M. Fellman ◽  
Ying Yuan ◽  
Anil K. Sood ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Dose Reduction ◽  
Phase Ii ◽  
Clinical Benefit ◽  
Parp Inhibitor ◽  
Objective Response ◽  
Cell Cycle Checkpoint ◽  
M Cell ◽  
Peritoneal Cancer ◽  
Grade 3

5505 Background: Wee1 phosphorylates and inhibits cyclin-dependent kinases 1 and 2 and is involved in regulation of the intra-S and G2/M cell cycle checkpoint arrest for premitotic DNA repair. The Wee1 inhibitor, adavosertib, has demonstrated activity alone and in combination with olaparib in PARP inhibitor (PARPi)-resistant preclinical models. We sought to evaluate efficacy of adavosertib (A) with or without olaparib (O) in a phase II noncomparative study of recurrent PARPi-resistant ovarian cancer. Methods: Women with recurrent ovarian, fallopian tube or primary peritoneal cancer with documented progressive disease on a PARPi were eligible. All patients (pts) had measurable disease and adequate end organ function. On the A arm, pts received A 300mg PO daily on days 1-5 and 8-12 of a 21-day cycle. On the A/O arm, pts received A 150mg PO BID on days 1-3 and 8-10 and O 200mg PO BID on days 1-21 of a 21-day cycle. Primary endpoint was objective response per RECIST 1.1 and was assessed every 2 cycles. Clinical benefit rate (CBR) was defined as proportion of pts with objective response or stable disease > 16 weeks. Progression free survival (PFS) was assessed using the Kaplan Meier method and calculated from date of treatment initiation to earliest date of progression, death, or last visit. Results: 116 pts were screened with 80 pts enrolled and randomized (A: n=39, A/O: n=41). Median age was 60 years (range 36-76) and the majority of pts had platinum resistant disease (64%) and high grade serous histology (98%). Pts received a median of 4 prior therapies (range 1-11) and 48% had germline or somatic BRCA mutations. There were 35 pts evaluable for response in each arm. Table demonstrates efficacy data. On the A arm, Grade 3/4 toxicities occurred in 51% of pts, most commonly neutropenia (13%), thrombocytopenia (10%), and diarrhea (8%). 28 (72%) pts required at least one dose interruption and 20 (51%) required dose reduction. On the A/O arm, Grade 3/4 toxicities occurred in 76% of pts, most commonly thrombocytopenia (20%), neutropenia (15%), diarrhea (12%), fatigue (12%), and anemia (10%). 36 (88%) of pts required at least one dose interruption, 29 (71%) required dose reduction, and 4 (10%) did not restart due to toxicity. Conclusions: A given alone and in combination with O demonstrated efficacy in pts with PARPi-resistant ovarian cancer. Although grade 3 and 4 toxicities were observed on both arms, these were generally manageable with supportive care, dose interruptions and dose reductions as needed. Additional translational analyses are ongoing to clarify which pts received clinical benefit. Clinical trial information: NCT03579316. [Table: see text]

Phase II study of trabectedin in pretreated patients with recurrent epithelial ovarian cancer (REOC).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 5559-5559
Author(s):  
Marco Marinaccio ◽  
Emilia Mele ◽  
Vito Lorusso ◽  
Valeria Vincenza Fumarulo ◽  
Fausta Sozzi ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Partial Response ◽  
Epithelial Ovarian Cancer ◽  
Phase Ii ◽  
Stable Disease ◽  
Phase Ii Study ◽  
Single Agent ◽  
Objective Response ◽  
Response To Treatment ◽  
Open Label

5559 Background: The prognosis of patients with REOC is extremely poor after several lines of chemotherapy. The choice and timing of therapies must be individualized to optimize survival and quality of life. This open-label, nonrandomized, phase II study was aimed at evaluating efficacy and toxicity of Trabectedin as a single-agent therapy in patients with preteated Recurrent Epithelial Ovarian Cancer (REOC). Methods: Sixteen patients (median age 51 yrs, range 44 – 71) with REOC who progressed after 2 (18.7%), 3 (56.3%) or 4 (25.0%) previous lines of chemotherapy were treated with Trabectedin at the dose of 1.1 mg/m2 via a 3-hour i.v. infusion with dexamethasone pretreatment every 3 weeks until disease progression, unacceptable toxicity or when a stability of disease was reached. Clinical objective response was the primary efficacy endpoint; the secondary one was safety. Response to treatment was assessed according to Response Evaluation Criteria in Solid Tumours (RECIST, version 1.1), and toxicities were graded according to NCI Common Toxicity Criteria, version 2.0. Results: The median number of treatment cycles per patients was 5 (range, 2-9 cycles). A total of 81 cycles were administered. A dose reduction was never required. Main toxicities included anemia (20.9%), leucopenia (15.0%), thrombocytopenia (4.5%) and asthenia (22.2%). No deaths were attributable to therapy. No one showed complete response, while 9/16 partial response (56.2%) and 4/16 stable disease (25.0%) were observed. 3/19 pts (18.8%) progressed on therapy. The median progression-free interval was 18 weeks in patients with partial response; stable disease was maintained for a median time of 12 weeks. Conclusions: Trabectedin 1.1mg/m2 given as a 3-hour i.v. infusion every 3 weeks was well tolerated and has confirmed a very interesting antitumor activity in this heavily pretreated population and it seems also to be a very tolerable regimen. The co-treatment with dexamethasone improves the safety of Trabectedin by reducing drug-induced myelosuppression and hepatotoxicity. Trabectedin has a manageable toxicity profile, and can be safely administered thanks to its secure action profile also in patients with no other viable therapeutic options.

Final results of a phase II trial of first-line FOLFIRINOX for advanced gastroesophageal cancers.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 4532-4532
Author(s):  
Ramon Jin ◽  
Haeseong Park ◽  
Andrea Wang-Gillam ◽  
Rama Suresh ◽  
Caron E. Rigden ◽  
...  
Keyword(s):  
Phase Ii ◽  
Clinical Benefit ◽  
Objective Response ◽  
Sensory Neuropathy ◽  
Progression Free Survival ◽  
Complete Response ◽  
Clinical Activity ◽  
First Line ◽  
Her2 Positive ◽  
Open Label

4532 Background: Standard first-line regimens for patients with metastatic gastroesophageal adenocarcinomas have moderate clinical benefit with objective response rates (ORR) of approximately 40-50%. FOLFIRINOX has been shown to be an effective and well-tolerated first line therapy in other GI cancers. In this open-label, single-arm phase II study of patients with advanced gastroesophageal adenocarcinomas, we sought to evaluate the safety and clinical activity of FOLFIRINOX. Methods: The primary endpoint was ORR, and secondary endpoints included safety profile, progression free survival (PFS), overall survival (OS), time to progression (TTP), clinical benefit rate (CBR), and duration of response. Estimated sample size included 41 patients with HER2 negative disease with 90% power to detect an ORR≥60% with alpha of 0.10. No enrollment goal was planned for HER2 positive patients, but they were allowed participation to receive study treatment in combination with trastuzumab. Treatment consisted of 400mg/m2 5-FU bolus, 400 mg/m2 leucovorin, 2400 mg/m2 5-FU infusion over 46 hours, 180 mg/m2 irinotecan, and 85 mg/m2 oxaliplatin. Trastuzumab was administered intravenously as a 6 mg/kg loading dose then given 4 mg/kg every 14 days for HER2 positive patients. This trial is registered with ClinicalTrials.gov, NCT01928290. Results: From November 2013 to May 2019, 67 patients were enrolled, of which 26 (39%) had HER2 positive disease. Median follow-up was 16.1 months. ORR was 61% (25/41) for HER2 negative and 85% (22/26) for HER2 positive groups. Overall, one patient (2%) had a complete response, 36 patients (69%) had partial responses, and 13 patients (19%) had stable disease for >6 months; therefore, CBR was 96%. Median PFS was 11.9 months, median OS was 17.4 months. 41 patients (83.7%) had dose modification or treatment delay with the most common toxicities being neutropenia, diarrhea, peripheral sensory neuropathy, and nausea with no unexpected toxicities. Conclusions: FOLFIRINOX is a highly effective three-drug regimen for first-line treatment of advanced gastroesophageal cancer with expected, tolerable toxicities. Clinical trial information: NCT01928290 .

scholarly journals LGG-49. SAFETY AND EFFICACY OF TRAMETINIB (T) MONOTHERAPY AND DABRAFENIB + TRAMETINIB (D+T) COMBINATION THERAPY IN PEDIATRIC PATIENTS WITH BRAF V600-MUTANT LOW-GRADE GLIOMA (LGG)

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii375-iii375
Author(s):  
Eric Bouffet ◽  
James A Whitlock ◽  
Christopher Moertel ◽  
Birgit Geoerger ◽  
Isabelle Aerts ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Pediatric Patients ◽  
Objective Response ◽  
Safety Data ◽  
Dose Finding ◽  
Combination Group ◽  
Clinical Activity ◽  
Low Grade ◽  
Open Label ◽  
Independent Review

Abstract BACKGROUND Children with BRAF V600-mutant LGG have suboptimal response to standard chemotherapy. Previously, D (BRAF V600 inhibitor) monotherapy has demonstrated clinical benefit in this population. We report interim analysis results of pediatric patients with recurrent/refractory BRAF V600-mutant LGG treated with either T (MEK1/2 inhibitor) monotherapy or D+T combination therapy. METHODS This is a 4-part, open-label, multicenter, phase I/II study (NCT02124772) in pediatric patients (&lt;18 y) with refractory/recurrent tumors. The dose-finding phase, including dose confirmation stratified by age, was followed by disease-specific cohorts at recommended dose levels. Efficacy was determined by both investigator and independent review using RANO criteria. Adverse events (AEs) were assessed per NCI-CTCAE v4.03. RESULTS Of 49 pediatric patients with BRAF V600-mutant LGG (T, n=13; D+T, n=36) enrolled, pooled efficacy data was available for both treatments while safety data was available for 30 patients (T, n=10; D+T, n=20). Most patients (n=8/10) receiving T monotherapy withdrew/discontinued the treatment in contrast to 3/20 in the D+T group. Pyrexia occurred in 50% of patients (n=5/10) in the monotherapy group and was a frequent AE in the combination group (75%; n=15/20). Objective response rate per independent review was 15% (95% CI, 2%–45%) with T monotherapy and 25% (95% CI, 12%–42%) with D+T combination therapy. Seven patients (54%) on monotherapy and 33 patients (92%) on combination therapy had stable disease or better. CONCLUSION In pediatric patients with previously treated BRAF V600-mutant LGG, T monotherapy and D+T combination therapy demonstrated clinical activity, with pyrexia being a common AE.

795 A multicenter phase II trial (SWOG S1609, cohort 51) of ipilimumab and nivolumab in metastatic or unresectable angiosarcoma: a substudy of dual anti-CTLA-4 and anti-PD-1 blockade in rare tumors (DART)

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A843-A843
Author(s):  
Michael Wagner ◽  
Megan Othus ◽  
Sandip Patel ◽  
Christopher Ryan ◽  
Ashish Sangal ◽  
...  
Keyword(s):  
Phase Ii ◽  
Immune Checkpoint ◽  
Uv Light ◽  
Light Exposure ◽  
Case Reports ◽  
Objective Response ◽  
Open Label ◽  
Primary Tumors ◽  
Multicenter Phase ◽  
Grade 3

BackgroundAngiosarcoma is a rare cancer of endothelial cells that can be aggressive and carries a high mortality. A subset of angiosarcomas are characterized by high tumor mutational burden (TMB) and UV light exposure DNA mutational signature. Isolated case reports have suggested clinical efficacy of immune checkpoint blockade in angiosarcoma; no prospective studies of immune checkpoint inhibition in angiosarcoma have been reported. We report efficacy analysis results for patients with advanced or unresectable angiosarcoma treated with ipilimumab and nivolumab as a cohort of an ongoing phase II study for rare cancers (NCT02834013).MethodsThis is a prospective, open-label, multicenter phase II clinical trial of ipilimumab (1mg/kg IV q6weeks) plus nivolumab (240mg IV q2weeks) for patients with metastatic or unresectable angiosarcoma. Primary endpoint is objective response rate as assessed by RECIST v1.1, including measurable cutaneous disease that can be followed by photography. Secondary endpoints include PFS, OS, stable disease at six months, and toxicity. A two-stage design is used with six patients in the first stage and an additional ten patients in the second stage.ResultsAt data cutoff, 16 patients with angiosarcoma were enrolled. Median age was 68 years (25-81 years). Median number of prior lines of therapy was 2 (0-5). 9 patients had cutaneous primary tumors of any cutaneous site, 7 had non-cutaneous primary tumors. ORR for all patients was 25% (4/16, table 1, figure 1). Subgroup analysis revealed that 60% (3/5) of patients with primary cutaneous tumors of the scalp or face had a confirmed objective response. 6-month PFS was 38%. 75% of patients experienced an adverse event (AE), and 25% experienced a grade 3-4 AE. 68.8% experienced an immune related AE (irAE), and 2 (12.5%) developed grade 3 or 4 irAEs. Grade 3-4 irAEs were ALT and AST increase and diarrhea. There were no grade 5 toxicities.ConclusionsThe combination of ipilimumab and nivolumab was well tolerated and had an ORR of 25% in angiosarcoma regardless of primary site, with 3 of 5 patients with cutaneous tumors of the scalp or face responding. Ipilimumab and nivolumab warrant further investigation in angiosarcoma.AcknowledgementsFunding: National Institutes of Health/National Cancer Institute grant awards CA180888, CA180819, CA180868; and in part by Bristol-Myers Squibb CompanyTrial RegistrationNCT02834013Ethics ApprovalThis study was approved by the NCI CIRB.

Regomune: A phase II study of regorafenib + avelumab in solid tumors—Results of the biliary tract cancer (BTC) cohort.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 4096-4096
Author(s):  
Sophie Cousin ◽  
Carine A. Bellera ◽  
Jean Philippe Guégan ◽  
Thibault Mazard ◽  
Carlos A. Gomez-Roca ◽  
...  
Keyword(s):  
Phase Ii ◽  
Adaptive Design ◽  
Objective Response ◽  
Locally Advanced ◽  
Survival Rates ◽  
Previous Treatment ◽  
Progression Free Survival ◽  
Treatment Interruption ◽  
Clinical Activity ◽  
Open Label

4096 Background: Regorafenib (R) has shown promising efficacy in patients (pts) with BTC refractory to standard chemotherapy. Anti-PD1/PD-L1 antibodies have only limited clinical activity. Synergy between R and anti–PD-1/PD-L1 antibodies has been shown in pre-clinical solid tumor models. Methods: This is a single-arm open-label multicentric phase II trial (Bayesian adaptive design) assessing the efficacy and safety of R (160 mg QD 3weeks/4) + avelumab (A) (10 mg/kg every 2 weeks) combination in BTC pts. The primary endpoint was the objective response rate under treatment, based on central review according to RECIST 1.1. Secondary endpoints included: 1-year progression free survival (PFS), 1-year overall survival (OS), and Safety using NCI-CTCAE v5.0. Correlative studies were planned from pts tumor samples obtained at baseline. Results: Between Nov. 2018 and Nov. 2019, 34 BTC pts were enrolled in 4 centers. Median age was 63 (range 36 – 80). Median follow-up was 9.8 months. Median number of previous treatment lines for metastatic or locally advanced disease was: 2 (range 1 – 4). Twenty-nine (85.3%) pts experienced at least 1 dose modification or treatment interruption of R or A due to an adverse event (AE) related to the treatment. The most common grade 3/4 AEs were : Hypertension (17.6%), Fatigue (14.7%), and maculo-papular rash (11.8%). No death was related to the treatment. Among the 29 pts with at least one imaging tumor assessment, 4 (13.8%) achieved a partial response, and 11 (37.9%) demonstrated stable disease including 10 (34.5%) pts with tumor shrinkage. Fourteen pts (48.3%) had progressive disease. The median PFS and OS were 2.5 months (95%CI 1.9 – 5.5) and 11.9 months (95%CI 6.2 – NA) respectively. Baseline tumor samples were available for 27 pts. High IDO and PD-L1 expression at baseline was associated with better outcome. Conclusions: The R+A combination is associated with significant anti-tumor activity with promising survival rates in this heavily pre-treated population. Full Biomarkers analyses will be presented at the meeting. Clinical trial information: NCT03475953.

Selinexor in combination with weekly paclitaxel in patients with advanced or metastatic solid tumors: Results of an open label, single-center, multiarm phase 1b study.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 5565-5565
Author(s):  
Shannon Neville Westin ◽  
Siqing Fu ◽  
Apostolia Maria Tsimberidou ◽  
Sarina Anne Anne Piha-Paul ◽  
Fechukwu Akhmedzhanov ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Solid Tumors ◽  
Clinical Benefit ◽  
Nuclear Export ◽  
Nuclear Accumulation ◽  
Weekly Paclitaxel ◽  
Clinical Activity ◽  
Single Center ◽  
Open Label ◽  
Phase 1B

5565 Background: Selinexor is a first-in-class novel, oral potent selective inhibitor of nuclear export (SINE) which blocks Exportin-1 (XPO1) leading to nuclear accumulation and activation of tumor suppressor proteins and prevention of translation of proto-oncogenes. Weekly paclitaxel is a standard chemotherapy regimen used in various tumor types. Preclinical models show that selinexor with paclitaxel exerts antitumor activity against multiple solid tumors. Our objective was to determine the maximum tolerated dose (MTD) and recommended phase II dose (RP2D) of selinexor and weekly paclitaxel. Methods: This was an open label, single-center, multi-arm phase 1b study utilizing a “3 + 3” design and a “basket type” expansion. Selinexor (twice weekly orally) and weekly paclitaxel (80mg IV 2 week on, 1 week off) was employed as one of 13 parallel arms. Two dose levels (DL) of selinexor were explored: DL1 selinexor 60mg; DL2 selinexor 80mg. Patients (pts) with advanced or metastatic solid tumors were eligible if they had adequate bone marrow and organ function. There was no limit on prior lines of therapy. Efficacy was evaluated using RECIST 1.1. Progression free survival (PFS) was defined as time from treatment until disease progression or death. Results: Of 35 pts treated, all were evaluable for toxicity, and 31 (88%) were evaluable for response. Pt diagnoses included ovarian (n = 28), breast (n = 4), prostate (n = 2), and cervical (n = 1) cancer. Pts had a median of four prior therapies (range 1-10), and 47% had a prior taxane. All pts with ovarian cancer had platinum resistant/refractory disease; high grade serous histology was most common. There were no DLTs and DL1 was chosen as the RP2D given its long term tolerability. 97% of pts had at least one treatment-emergent adverse event (TEAE) and the most common TEAEs were anemia (74%), nausea (57%), fatigue (51%), leukopenia (51%), neutropenia (49%), thrombocytopenia (46%), and vomiting (31%). The most prevalent grade ≥ 3 TEAE were neutropenia (46%), anemia (31%), leukopenia (17%), and fatigue (9 %). Partial responses (PR) were noted in 4 pts (13%); 10 pts (32%) achieved stable disease for > 4 months for a clinical benefit rate (CBR) of 45%. 16 pts (47%) had prior exposure to a taxane, including 1 pt who achieved PR. Among 24 evaluable pts with ovarian cancer, response rate was 17%, CBR was 58%, and PFS was 6.83 months (95% CI 3.73, not reached (NR)). Median duration of clinical benefit in ovarian cancer was 7.57 months (95% CI: 4.43, NR). Conclusions: Oral selinexor in combination with weekly paclitaxel demonstrated promising clinical activity with manageable toxicity, and further evaluation with once weekly selinexor is warranted. This combination should be considered for further exploration in a randomized study, especially in ovarian malignancies. Clinical trial information: NCT02419495.

PULSE: A randomized phase II open label study of panitumumab rechallenge versus standard therapy after progression on anti-EGFR therapy in patients with RAS wild-type metastatic colorectal cancer (mCRC).

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. TPS143-TPS143
Author(s):  
John H. Strickler ◽  
Fang-Shu Ou ◽  
Tanios S. Bekaii-Saab ◽  
Christine Megerdichian Parseghian ◽  
Andrea Cercek ◽  
...  
Keyword(s):  
Phase Ii ◽  
Clinical Benefit ◽  
Objective Response ◽  
Progression Free Survival ◽  
Wild Type ◽  
Open Label ◽  
Genomic Alterations ◽  
Open Label Study ◽  
Label Study ◽  
Randomized Phase Ii

TPS143 Background: Patients with KRAS and NRAS ( RAS) wild-type mCRC benefit from the epidermal growth factor receptor (EGFR) monoclonal antibodies (Abs) panitumumab and cetuximab, but nearly all patients experience resistance. Blood-based profiling of cell free DNA (cfDNA) can identify genomic alterations that drive acquired EGFR Ab resistance. After discontinuation of anti-EGFR Abs, acquired genomic alterations decay over time to undetectable levels. Some studies have suggested clinical benefit from EGFR Ab rechallenge, but there is limited evidence that EGFR Ab rechallenge improves survival compared to standard of care (SOC) therapies. We hypothesize that cfDNA profiling will identify patients appropriate for panitumumab rechallenge, and that these molecularly selected patients will have improved survival compared to current SOC therapies. Methods: This is a randomized phase II, open label study designed to compare the overall survival (OS) of panitumumab rechallenge versus SOC (investigator choice TAS-102 or regorafenib). Secondary objectives include comparisons of progression free survival, objective response rate, clinical benefit rate, and quality of life as measured by the linear analogue self-assessment (LASA) questionnaire. Eligible patients have radiographically measurable KRAS, NRAS, and BRAF codon 600 wild-type mCRC based on tumor tissue testing, and must have experienced progression or intolerance to treatment with a fluoropyrimidine, oxaliplatin, irinotecan, an anti-VEGF Ab, and an anti-PD-1 Ab if the tumor has mismatch repair deficiency or is MSI-H. Progression after at least 4 months treatment with an anti-EGFR Ab is required. All patients must be enrolled in the COLOMATE cfDNA screening protocol (NCT03765736) and meet molecular eligibility based on Guardant360 cfDNA profiling (absence of amplification of ERBB2, KRAS, NRAS, and MET; absence of mutations of BRAF, EGFR, ERBB2, KRAS, NRAS, and MET [mutant allele frequency > 0.5%]). Greater than 90 days must have elapsed between the most recent treatment with an anti-EGFR Ab and cfDNA profiling. Dosing for all study drugs is according to clinical SOC. 120 patients will be randomized 1:1 to panitumumab rechallenge or SOC. With 83 OS events, this study will have 80% power to detect an improvement in median OS from 6.5 to 10 months (HR=0.65; 1-sided α= 0.15). This study began enrollment in 6/2020. Recruitment is ongoing at 16 sites in the Academic and Community Cancer Research United (ACCRU) network (ACCRU-GI-1623). Clinical trial information: NCT03992456.

scholarly journals Pyrotinib in HER2-Mutant Advanced Lung Adenocarcinoma After Platinum-Based Chemotherapy: A Multicenter, Open-Label, Single-Arm, Phase II Study

2020 ◽  
Vol 38 (24) ◽  
pp. 2753-2761 ◽  
Author(s):  
Caicun Zhou ◽  
Xingya Li ◽  
Qiming Wang ◽  
Guanghui Gao ◽  
Yiping Zhang ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Phase Ii ◽  
Objective Response Rate ◽  
Response Rate ◽  
Phase Ii Study ◽  
Objective Response ◽  
Unmet Need ◽  
Open Label ◽  
Platinum Based Chemotherapy ◽  
Grade 3

PURPOSE Targeted therapies against non–small-cell lung cancer (NSCLC) harboring HER2 mutations remain an unmet need. In this study, we assessed the efficacy and safety of pyrotinib in patients with HER2-mutant advanced NSCLC in a prospective, multicenter, open-label, single-arm, phase II study. PATIENTS AND METHODS Patients with stage IIIB or IV HER2-mutant lung adenocarcinoma who were previously treated with platinum-based chemotherapy were enrolled to receive pyrotinib at a dose of 400 mg/d for 21-day cycles. The primary end point was objective response rate per independent review committee (IRC). RESULTS Between October 20, 2016, and December 10, 2018, 60 patients received pyrotinib monotherapy. At baseline, 58 (96.7%) were stage IV, and 25 (41.7%) received at least 2 lines of prior chemotherapy. As of data cutoff on June 20, 2019, IRC-assessed objective response rate was 30.0% (95% CI, 18.8% to 43.2%). All subgroups of patients with different HER2 mutation types showed a favorable objective response rate. The objective response rates were similar between patients with and without brain metastases (25.0% v 31.3%). The median duration of response was 6.9 months (95% CI, 4.9 to 11.1 months). The median progression-free survival was 6.9 months (95% CI, 5.5 to 8.3 months) per IRC. The median overall survival was 14.4 months (95% CI, 12.3 to 21.3 months). Treatment-related adverse events of grade 3 or 4 occurred in 28.3% of patients, with the most common being diarrhea (20.0%; all grade 3). No treatment-related deaths were reported. CONCLUSION Pyrotinib showed promising antitumor activity and an acceptable safety profile in chemotherapy-treated patients with HER2-mutant NSCLC.

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