Pertuzumab plus trastuzumab (P+T) in patients (Pts) with uterine cancer (UC) with ERBB2 or ERBB3 amplification, overexpression or mutation: Results from the Targeted Agent and Profiling Utilization Registry (TAPUR) study.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 5508-5508
Author(s):  
Hussein Moustapha Ali-Ahmad ◽  
Michael Rothe ◽  
Pam K. Mangat ◽  
Liz Garrett-Mayer ◽  
Eugene Ahn ◽  
...  
Keyword(s):  
Initial Dose ◽  
Uterine Cancer ◽  
Treatment Options ◽  
Objective Response ◽  
Progression Free Survival ◽  
Complete Response ◽  
Grade 3 ◽  
Ecog Ps ◽  
Anti Tumor Activity ◽  
Erbb2 Amplification

5508 Background: TAPUR is a phase II basket study evaluating anti-tumor activity of commercially available targeted agents in pts with advanced cancers with genomic alterations. Results in a cohort of UC pts with ERBB2 or ERBB3 amplification , overexpression or mutation treated with P+T are reported. Methods: Eligible pts had advanced UC, no standard treatment options, measurable disease, ECOG PS 0-2, and adequate organ function. Genomic testing was performed in CLIA-certified, CAP-accredited site selected labs. Pts matched to P+T had UC with ERBB2 or ERBB3 amplification or overexpression or a pre-specified ERBB2 mutation. Recommended dosing was P at an initial dose of 840 mg intravenously (IV) over 60 minutes (m), then 420 mg IV over 30-60 m every 3 weeks (wks), and T at an initial dose of 8 mg/kg IV over 90 m, then 6 mg/kg IV over 30-60 m every 3 wks until disease progression. Simon 2-stage design tested the null disease control (DC) - defined as partial (PR), complete response (CR) or stable disease at 16+ weeks (SD 16+) - rate of 15% vs. 35% (power = 0.85; α = 0.10). If ≥2 of 10 pts in stage 1 have DC, 18 more pts are enrolled. If ≥7 of 28 pts have DC, the null DC rate is rejected. Secondary endpoints are progression-free survival (PFS), overall survival (OS) and safety. Results: Twenty-eight female pts were enrolled from August 2017 to November 2019; all pts were evaluable for efficacy and toxicity. Demographics and outcomes are summarized in Table. Twenty-two pts had tumors with ERBB2 amplification (21) or overexpression (1); 4 tumors had ERBB2 mutations; 1 tumor had ERBB3 amplification; 1 tumor had both an ERBB2 amplification and mutation. Two PR and 7 SD16+ were observed in pts with ERBB2 amplification, and 1 SD16+ was observed in a pt with ERBB2 V8421 mutation only (no amplification) for DC and objective response (OR) rates of 37% (95% CI, 21% to 50%) and 7.1% (95% CI, 0.8% to 24%), respectively. One pt experienced grade 3 muscle weakness at least possibly related to P+T. Conclusions: P+T demonstrated evidence of anti-tumor activity in heavily pre-treated UC pts with ERBB2 amplification or certain mutations. Additional study is warranted to confirm the efficacy of P+T in this pt population. Clinical trial information: NCT02693535. [Table: see text]

Palbociclib (P) in patients (pts) with soft tissue sarcoma (STS) with CDK4 amplification: Results from the Targeted Agent and Profiling Utilization Registry (TAPUR) study.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 11565-11565
Author(s):  
Scott Schuetze ◽  
Michael Rothe ◽  
Pam K. Mangat ◽  
Liz Garrett-Mayer ◽  
Funda Meric-Bernstam ◽  
...  
Keyword(s):  
Treatment Options ◽  
Objective Response ◽  
Progression Free Survival ◽  
Complete Response ◽  
Stage Design ◽  
Secondary Endpoints ◽  
Grade 3 ◽  
Ecog Ps ◽  
Stage 1 ◽  
Anti Tumor Activity

11565 Background: TAPUR is a phase II basket study evaluating anti-tumor activity of commercially available targeted agents in pts with advanced cancers with genomic alterations. Results in a cohort of STS pts with CDK4 amplification treated with P are reported. Methods: Eligible pts had advanced STS, no standard treatment options, measurable disease, ECOG PS 0-2, and adequate organ function. Genomic testing was performed in CLIA-certified, CAP-accredited site selected labs. Pts received P at 125 mg orally once daily for 21 days, followed by 7 days off until disease progression. Pts matched to P had CDK4 amplification and no RB mutations. Simon 2-stage design tested the null disease control (DC) - defined as partial (PR), complete response (CR) or stable disease at 16+ weeks (SD 16+) - rate of 15% vs. 35% (power = 0.85; α = 0.10). If ≥2 of 10 pts in stage 1 have DC, 18 more pts are enrolled. If ≥7 of 28 pts have DC, the null DC rate is rejected. Secondary endpoints are progression-free survival (PFS), overall survival (OS) and safety. Results: 29 pts (66% male) with STS with CDK4 amplification were enrolled from July 2016 to Nov 2019. 1 pt was not evaluable and excluded from efficacy analyses. Demographics and outcomes are summarized in Table. One pt with partial response (PR) and 12 pts with SD16+ were observed for DC and objective response (OR) rates of 48% (95% CI: 31%, 62%) and 3.7% (95% CI: 0.1%, 19%), respectively, and the null DC rate of 15% was rejected (p<0.001). 9/13 pts with DC continued on treatment for >32 weeks. 14 pts had at least one grade 3-4 AE at least possibly related to P with the most common being low WBC/platelets. Other grade 3 AEs included increased alanine aminotransferase, anemia, and fatigue. Conclusions: Monotherapy P demonstrated anti-tumor activity in heavily pre-treated pts with STS with CDK4 amplification. Additional study is warranted to confirm the efficacy of P in pts with STS with CDK4 amplification. Clinical trial information: NCT02693535. [Table: see text]

Palbociclib (P) in patients (pts) with head and neck cancer (HNC) with CDKN2A loss or mutation: Results from the Targeted Agent and Profiling Utilization Registry (TAPUR) study.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 6043-6043
Author(s):  
Evan P. Pisick ◽  
Michael Rothe ◽  
Pam K. Mangat ◽  
Liz Garrett-Mayer ◽  
Francis P. Worden ◽  
...  
Keyword(s):  
Lung Metastases ◽  
Treatment Options ◽  
Objective Response ◽  
Progression Free Survival ◽  
Complete Response ◽  
Clinically Significant ◽  
Grade 3 ◽  
Ecog Ps ◽  
Stage 1 ◽  
Anti Tumor Activity

6043 Background: TAPUR is a phase II basket study evaluating anti-tumor activity of commercially available targeted agents in pts with advanced cancers with genomic alterations. Results in a cohort of HNC pts with CDKN2A loss or mutation treated with P are reported. Methods: Eligible pts had advanced HNC, no standard treatment options, measurable disease, ECOG PS 0-2, and adequate organ function. Genomic testing was performed in CLIA-certified, CAP-accredited site selected labs. Pts received P at 125 mg orally once daily for 21 days, followed by 7 days off until disease progression. Pts matched to P had CDKN2A loss or mutation and no RB mutations. Simon 2-stage design tested the null disease control (DC) - defined as partial (PR), complete response (CR) or stable disease at 16+ weeks (SD 16+) - rate of 15% vs. 35% (power = 0.85; α = 0.10). If ≥2 of 10 pts in stage 1 have DC, 18 more pts are enrolled. If ≥7 of 28 pts have DC, the null DC rate is rejected. Secondary endpoints are progression-free survival (PFS), overall survival (OS) and safety. Results: 28 pts (64% male) with HNC with CDKN2A loss (20 pts) or mutation (8 pts) were enrolled from June 2016 to Sept 2019. All were eligible for efficacy and toxicity. Demographics and outcomes are summarized in Table. No objective response (OR) and 10 pts with SD16+ (9 with CDKN2A loss, 1 with mutation) were observed for a DC rate of 37% (95% CI: 21%, 50%); the null DC rate of 15% was rejected (p=0.005). 14 pts had at least one grade 3-5 adverse or serious adverse event (AE/SAE) at least possibly related to P with the most common being low WBC/platelets. Other grade 3-4 AEs included anemia, fatigue, hypocalcemia, and syncope. There was one pt with grade 5 respiratory failure likely due to extensive lung metastases and aspiration but P-related pneumonitis could not be ruled out. Conclusions: Monotherapy P demonstrated modest anti-tumor activity and clinically significant AEs in heavily pre-treated pts with HNC with CDKN2A loss or mutation. Additional study is warranted to confirm the efficacy of P in pts with HNC with CDKN2A loss or mutation. Clinical trial information: NCT02693535. [Table: see text]

Pertuzumab plus trastuzumab (P+T) in patients (Pts) with colorectal cancer (CRC) with ERBB2 amplification or overexpression: Results from the TAPUR Study.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 132-132 ◽  
Author(s):  
Ranju Gupta ◽  
Elizabeth Garrett-Mayer ◽  
Susan Halabi ◽  
Pam K. Mangat ◽  
Stacy D. D'Andre ◽  
...  
Keyword(s):  
Objective Response ◽  
Progression Free Survival ◽  
Infusion Reaction ◽  
Left Ventricular ◽  
Grade 3 ◽  
Ecog Ps ◽  
Stage 1 ◽  
Anti Tumor Activity ◽  
Erbb2 Amplification ◽  
Erbb2 Overexpression

132 Background: TAPUR is a phase II basket trial evaluating anti-tumor activity of commercially available targeted agents in pts with advanced cancers with genomic alterations. Results in a cohort of CRC pts with ERBB2 overexpression or amplification treated with P+T are reported. Methods: Eligible pts had advanced CRC, no standard treatment (tx) options, measurable disease, ECOG PS 0-2, and adequate organ function. Genomic testing was performed in CLIA-certified, CAP-accredited site selected labs. Pts had ERBB2 overexpression or amplification, or certain ERBB2 mutations. Recommended dosing after initial dosing was P, 420 mg IV over 30-60 mins every 3 weeks (wks) and T, 6 mg/kg over 30-60 mins every 3 wks. Simon two-stage design was used to test a null rate of 15% vs. 35% (power = 0.85; α = 0.10). If ≥2 of 10 pts in stage 1 have disease control (DC) (objective response (OR) or stable disease at 16+ wks per RECIST (SD16+)), 18 more pts enrolled. If ≥7 of 28 pts have DC, the tx is worthy of further study. Secondary endpoints are progression-free survival (PFS), overall survival (OS) and safety. Results: Twenty-eight pts enrolled from November 2016 to September 2018 were evaluable for efficacy and safety. Demographics and outcomes are summarized in Table. All pts had ERBB2 amplification; 1 also had an ERBB2 mutation. 79% of pts had at least 3 prior txs. Four PR and 10 SD16+ were observed for DC and OR rates of 50% (90% CI, 36% to 60%) and 14% (95% CI, 4% to 33%), respectively. Two pts had at least one grade 3 AE or SAE at least possibly related to P+T including anemia, infusion reaction, and left ventricular dysfunction. Conclusions: The combination of P+T showed anti-tumor activity in heavily pre-treated CRC pts with ERBB2 amplification . Additional analyses by RAS mutation status are pending. Further study is warranted to confirm efficacy of P+T in this population. Clinical trial information: NCT02693535. [Table: see text]

Palbociclib (P) in patients (pts) with non-small cell lung cancer (NSCLC) with CDKN2A alterations: Results from the Targeted Agent and Profiling Utilization Registry (TAPUR) Study.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 9041-9041 ◽  
Author(s):  
Eugene R Ahn ◽  
Pam K. Mangat ◽  
Elizabeth Garrett-Mayer ◽  
Susan Halabi ◽  
Elie G. Dib ◽  
...  
Keyword(s):  
Treatment Options ◽  
Objective Response ◽  
Progression Free Survival ◽  
Stage Design ◽  
Secondary Endpoints ◽  
Targeted Agent ◽  
Grade 3 ◽  
Ecog Ps ◽  
Stage 1 ◽  
Anti Tumor Activity

9041 Background: TAPUR is a phase II basket study evaluating anti-tumor activity of commercially available targeted agents in pts with advanced cancers with genomic alterations. Results in a cohort of NSCLC pts with CDKN2A loss or mutation treated with P are reported. Methods: Eligible pts had advanced NSCLC, no standard treatment options, measurable disease, ECOG PS 0-2 and adequate organ function. Genomic testing was performed using commercially available tests. Pts matched to P had NSCLC with CDKN2A loss or mutation and no RB mutations. A Simon two-stage design was used to test a null rate of 15% vs. 35% (power = 0.85; α = 0.10). If ≥2 of 10 pts in stage 1 have disease control (DC) (objective response (OR) or stable disease at 16 weeks (wks) (SD16+)), an additional 18 pts are enrolled. If ≥7 of 28 pts have DC, the drug is considered worthy of further study. Secondary endpoints are progression-free survival (PFS), overall survival (OS) and safety. Results: Twenty-nine pts were enrolled from January 2017 to June 2018; 1 pt was unevaluable for response but is included in safety analyses. Pts received P at 125 mg orally once daily for 21 days, followed by 7 days off. Demographics and outcomes are summarized in Table (N = 28). One PR and 6 SD16+ were observed for a DC rate of 29% (90% CI, 15% to 37%). 10 pts had at least one grade 3 or 4 AE or SAE at least possibly related to P with the most common being cytopenias. Other grade 3-4 AEs or SAEs at least possibly related to P included fatigue, anorexia, febrile neutropenia, myocardial infarction, sepsis, vomiting, and hypophosphatemia. Conclusions: Monotherapy with P demonstrated evidence of anti-tumor activity in heavily pre-treated NSCLC pts with CDKN2A loss or mutation . Additional study is warranted to confirm the efficacy of P in pts with NSCLC with CDKN2A loss or mutation. Clinical trial information: NCT02693535. [Table: see text]

Pembrolizumab (P) in patients (pts) with metastatic breast cancer (MBC) with high tumor mutational burden (HTMB): Results from the Targeted Agent and Profiling Utilization Registry (TAPUR) Study.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 1014-1014 ◽  
Author(s):  
Ajjai Shivaram Alva ◽  
Pam K. Mangat ◽  
Elizabeth Garrett-Mayer ◽  
Susan Halabi ◽  
Ricardo H. Alvarez ◽  
...  
Keyword(s):  
Checkpoint Inhibitor ◽  
Treatment Options ◽  
Objective Response ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Predictive Biomarker ◽  
Tumor Board ◽  
Tumor Mutational Burden ◽  
Ecog Ps ◽  
Anti Tumor Activity

1014 Background: TAPUR is a phase II basket study evaluating the anti-tumor activity of commercially available targeted agents in pts with advanced cancers with specific genomic alterations. P is an immune checkpoint inhibitor and HTMB is an emerging predictive biomarker for checkpoint inhibitor therapy. Results in a cohort of MBC pts with HTMB treated with P are reported. Methods: Eligible pts had advanced cancer, no standard treatment options, ECOG PS 0-1, measurable disease and acceptable organ function. Genomic testing was performed using commercially available tests selected by sites. Pts matched to P had HTMB defined as ≥9 mutations/megabase (Muts/Mb) by a FoundationOne test (n=20) or approved by the TAPUR Molecular Tumor Board for other tests (n=8). A Simon two-stage design was used to test a null rate of 15% vs. 35% (power = 0.85; α = 0.10). If ≥2 of 10 pts in stage 1 have disease control (DC) (objective response (OR) or stable disease at 16 weeks (wks) (SD16+)), an additional 18 pts are enrolled. If ≥7 of 28 pts have DC, the drug is considered worthy of further study. Secondary endpoints are progression-free survival (PFS), overall survival (OS) and safety. Results: Twenty-eight female MBC pts were enrolled from October 2016 to July 2018. Pts received P at 2 mg/kg (n=8) or 200 mg (n=20) IV over 30 minutes, every 3 wks. HTMB ranged from 9 to 37 Muts/Mb. Demographics and outcomes are summarized in Table (N=28). No relationship was observed between #Muts/Mb and PFS or OS. Two grade 3 AEs (weight loss and hypoalbuminemia) and 1 grade 2 SAE (urinary tract infection) were reported as at least possibly related to P. Conclusions: P demonstrated anti-tumor activity in heavily pre-treated MBC pts with HTMB . Additional study of P is warranted in MBC pts with HTMB. Clinical trial information: NCT02693535. [Table: see text]

Cobimetinib plus vemurafenib (C+V) in patients (Pts) with colorectal cancer (CRC) with BRAF V600E mutations: Results from the TAPUR Study.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 122-122 ◽  
Author(s):  
Kelsey Klute ◽  
Elizabeth Garrett-Mayer ◽  
Susan Halabi ◽  
Pam K. Mangat ◽  
Reza Nazemzadeh ◽  
...  
Keyword(s):  
Objective Response ◽  
Progression Free Survival ◽  
Braf V600e ◽  
Stage Design ◽  
Elevated Liver Enzymes ◽  
Secondary Endpoints ◽  
Grade 3 ◽  
Ecog Ps ◽  
Stage 1 ◽  
Anti Tumor Activity

122 Background: TAPUR is a phase II basket study evaluating anti-tumor activity of commercially available targeted agents in pts with advanced cancers with genomic alterations. Results in a cohort of CRC pts with BRAF V600E mutation treated with C+V are reported. Methods: Eligible pts had advanced CRC, no standard treatment (tx) options, measurable disease, ECOG PS 0-2, and adequate organ function. Genomic testing was performed in CLIA-certified, CAP-accredited site selected labs. Pts had BRAF V600E/D/K/R mutation and no MAP2K1/2, MEK1/2, NRAS mutations. Recommended dosing was C, 60 mg orally once daily for 21 days, 7 days off and V, 960 mg orally twice daily. Simon two-stage design was used to test the null rate of 15% vs. 35% (power = 0.85; α = 0.10). If ≥2 of 10 pts in stage 1 have disease control (DC) (objective response (OR) or stable disease at 16 weeks (wks) according to RECIST (SD16+)), 18 more pts enrolled. If ≥7 of 28 pts have DC, the tx is worthy of further study. Secondary endpoints are progression-free survival (PFS), overall survival (OS) and safety. Results: Thirty pts enrolled from August 2016 to August 2018; 2 were not evaluable for efficacy. Demographics and outcomes are summarized in Table. All pts had BRAF V600E mutations. Eight PR and 8 SD16+ were observed for DC and OR rates of 57% (90% CI, 43% to 67%) and 29% (95% CI, 13% to 49%), respectively. Twelve pts had at least 1 grade 3 AE or SAE at least possibly related to C+V including elevated liver enzymes, decreased lymphocytes, dyspnea, diarrhea, fatigue, hypercalcemia, hypophosphatemia, rash, photosensitivity, upper GI hemorrhage, and vomiting. Conclusions: The combination of C+V showed anti-tumor activity in heavily pre-treated CRC pts with BRAF V600E mutations . Further study is warranted to confirm the efficacy of C+V in this population. Clinical trial information: NCT02693535. [Table: see text]

scholarly journals 357 Toripalimab plus chemoradiotherapy in patients with recurrent or metastatic cervical cancer: a multicenter, open-label, single-arm, phase II trial

2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A384-A384
Author(s):  
Xiaoting Xu ◽  
Jian Huan ◽  
Hui Miao ◽  
Hao Wang ◽  
Yue Wang ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Treatment Options ◽  
Objective Response ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Complete Response ◽  
Open Label ◽  
Nccn Guidelines ◽  
Significant Difference ◽  
Grade 3

BackgroundRecurrent or metastatic cervical cancer patients who progressed after standard therapy have limited treatment options and poor prognosis with a 1-year survival rate ranging between 15% and 20%. This study evaluates the efficacy and safety of toripalimab plus chemoradiotherapy in patients with recurrent or metastatic cervical cancer (Clinical trial ID: ChiCTR2000029068)MethodsIn this open-label, single-arm, phase 2 study conducted at four radiotherapy centers in East China, eligible patients were confirmed by pathology and/or imaging for recurrent or metastatic cervical cancer. According to the first-line therapies for cervical cancer recommended by NCCN guidelines, all patients were received paclitaxel plus cisplatin regimen, with or without bevacizumab, combined with radiotherapy. After seven fractions radiotherapy at the recurrent or metastatic regions, 240 mg toripalimab every three weeks for six cycles or more were given in combination.ResultsBetween Jan 14th, 2020, and May 1st, 2021, 24 patients were enrolled. All patients were staged at the first visit, as seven patients were with FIGO (2018) stage I, 10 with stage II, 2 with stage III, 1 with stage IV, and 2 with unclear stage. Of 24 included patients, 22 (91.67%) had squamous cervical cancer. The median age was 55 (range, 33–72) years. As of May 31, 2021, median follow-up time was 8.5 months [95% CI: 2.3–10.1]. 14 (58.3%) of 24 patients who achieved an objective response, including 10 (41.7%) complete response (CR) and 4 (16.7%) partial response (PR). The median duration of response was not reached and 7 (29.1%) patients continued toripalimab treatment after the previous 6-cycle immunotherapy. The disease control rate was 75% (18/24). Median progression-free survival (PFS) was 8.61 months (95% CI: 4.14–not reached). For subgroup analysis, the median PFS was significantly prolonged in the CR/PR group compared with that in the SD/PD group [not reached (95% CI: 6.21–not reached) versus 5.5 months (95% CI: 2.69–6.870), P = 0.023]. There was no significant difference in the median PFS between patients who previously received radiotherapy (8.61 months) and those who didn’t (6.87 months) (P = 0.641). 8 (33.3%) patients had grade 3–4 treatment-related adverse events (TRAEs). The most common grade 3-4 TRAEs were myelosuppression (29.2%), hypertriglyceridemia (8.3%), hypoalbuminemia (4.2%), pneumonia (4.2%), and hypercholesterolemia (4.2%).ConclusionsToripalimab plus chemoradiotherapy showed promising antitumor activity and tolerable toxicities in patients with recurrent or metastatic cervical cancer.

Results from TreeTopp: A randomized phase II study of the efficacy and safety of varlitinib plus capecitabine versus placebo in second-line (2L) advanced or metastatic biliary tract cancer (BTC).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 4597-4597 ◽  
Author(s):  
Milind M. Javle ◽  
Do-Youn Oh ◽  
Masafumi Ikeda ◽  
Wei-Peng Yong ◽  
Nicola McIntyre ◽  
...  
Keyword(s):  
Treatment Options ◽  
Objective Response ◽  
Group Analysis ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Double Blind ◽  
Tract Cancer ◽  
Early Results ◽  
Grade 3 ◽  
Ecog Ps

4597 Background: Patients with advanced or metastatic BTC who progress on first-line (1L) gemcitabine-based doublet chemotherapy have few 2L treatment options. Varlitinib is a reversible small molecule pan human epidermal growth factor receptor (HER) inhibitor with low nanomolar potency against HER1 (EGFR), HER2 and HER4 with promising early results in advanced BTC. Methods: TreeTopp (NCT03093870) was a global, multicenter, double blind phase 2 study in which patients with advanced BTC who progressed after 1L therapy that included ≥6 doses of gemcitabine, with radiographically measurable disease based on RECIST v1.1, ECOG PS 0 or 1 and albumin ≥3 g/dL were randomized (1:1) to varlitinib (300 mg BID) plus capecitabine (1000 mg/m2 BID 14 days on/ 7 off)(V+C) or placebo plus capecitabine (P+C). The dual primary endpoints were Objective Response Rate (ORR) and Progression Free Survival (PFS) defined as the time from randomization to radiological progression assessed by Independent Central Review. Secondary end points included Overall Survival (OS). Results: Overall, 127 patients were randomized (V+C, n = 64; P+C, n = 63) from May−Dec 2018 and demographics/baseline characteristics were generally well balanced, although the V+C arm had a lower proportion of females vs. P+C (31% vs. 48%). The odds ratio for ORR was numerically higher with V+C vs. P+C was 2.278 (9.4% vs. 4.8%, p = 0.42), the HR for PFS for V+C vs. P+C was 0.90 (median PFS, 2.8 vs. 2.8 months; p = 0.63), and the HR for OS for P+C vs. V+C was 1.11 (median OS, 7.8 vs. 7.5 months; p = 0.66). Although not powered to evaluate sub-group interactions, in sub-group analysis, V+C showed PFS benefit versus P+C in two sub-groups; gallbladder cancer (GBC, HR = 0.55, 95% CI: 0.25, 1.22; median PFS, 2.9 vs. 1.6 months) and females (HR = 0.59, 95% CI: 0.28, 1.23; median PFS, 4.1 vs. 2.8 months). There was no PFS benefit for V+C vs. P+C among males and non-GBC. Toxicities were generally balanced between arms apart from a slightly higher incidence of hyperbilirubinemia, diarrhea and fatigue in the V+C vs. P+C arm. Grade 3/4 toxicities were reported in 66% and 59% of patients in the V+C and P+C arms, respectively. Conclusions: V+C is well tolerated but did not improve ORR, PFS or OS vs. P+C in 2L advanced BTC. Exploratory analyses suggested that patients with GBC and female patients achieved comparatively higher median PFS with V+C vs. P+C. Clinical trial information: NCT03093870 .

Pembrolizumab (P) in patients (Pts) with colorectal cancer (CRC) with high tumor mutational burden (HTMB): Results from the Targeted Agent and Profiling Utilization Registry (TAPUR) Study.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 133-133 ◽  
Author(s):  
Eyal Meiri ◽  
Elizabeth Garrett-Mayer ◽  
Susan Halabi ◽  
Pam K. Mangat ◽  
Sagun Shrestha ◽  
...  
Keyword(s):  
Objective Response ◽  
Kidney Injury ◽  
Progression Free Survival ◽  
Tumor Board ◽  
Tumor Mutational Burden ◽  
Secondary Endpoints ◽  
Grade 3 ◽  
Ecog Ps ◽  
Stage 1 ◽  
Anti Tumor Activity

133 Background: TAPUR is a phase II basket study evaluating anti-tumor activity of commercially available targeted agents in pts with advanced cancers with genomic alterations. Results in a cohort of CRC pts with HTMB treated with P are reported. Methods: Eligible pts had advanced CRC, no standard treatment (tx) options, measurable disease, ECOG PS 0-1, and adequate organ function. Genomic testing was performed in CLIA-certified, CAP-accredited site selected labs. Pts had HTMB, defined as ≥9 mutations/megabase (Muts/Mb) by a FoundationOne test (n=26) or other tests (n=2) approved by the Molecular Tumor Board. Pts with MSI-H tumors were ineligible. Dosing of P was 2 mg/kg (n=8) or 200 mg (n=20) IV over 30 mins, every 3 wks. Simon two-stage design was used to test a null rate of 15% vs. 35% (power = 0.85; α = 0.10). If ≥2 of 10 pts in stage 1 have disease control (DC) (objective response (OR) or stable disease at 16+ wks according to RECIST (SD16+)), 18 more pts enrolled. If ≥7 of 28 pts have DC, the tx is worthy of further study. Secondary endpoints are progression-free survival (PFS), overall survival (OS) and safety. Results: Twenty-eight pts enrolled from June 2017 to November 2018; 1 pt was ineligible and excluded. HTMB ranged from 9 to 54 Muts/Mb. Table (N=27) summarizes demographics and outcomes. Tumor MS status was reported stable for 25 pts, ambiguous for 1 pt, and not available for 1 pt. One PR (MS stable and 10 Muts/Mb) and 7 SD16+ were observed for DC and OR rates of 28% (90% CI, 16% to 45%) and 4% (95% CI, 0% to 19%), respectively. 2 pts each had grade 3 AEs at least possibly related to P including abdominal infection, anorexia, colitis, diarrhea, fatigue, nausea, and vomiting; 1 also had SAE of acute kidney injury. Conclusions: Monotherapy with P showed anti-tumor activity in heavily pre-treated CRC pts with HTMB . Additional study is warranted to confirm the efficacy of P in this population. Clinical trial information: NCT02693535. [Table: see text]

Endometriumkarzinom: Kombination aus Lenvatinib und Pembrolizumab zeigt Wirksamkeit unabhängig vom Mikrosatellitenstatus

2021 ◽  
pp. 1-2
Author(s):  
Sarah Matz
Keyword(s):  
Endometrial Carcinoma ◽  
Treatment Options ◽  
Objective Response ◽  
Progression Free Survival ◽  
Efficacy Analysis ◽  
Duration Of Response ◽  
Previously Treated Patients ◽  
Previously Treated ◽  
Prior Systemic Therapy ◽  
Grade 3

<b>Purpose:</b> Patients with advanced endometrial carcinoma have limited treatment options. We report final primary efficacy analysis results for a patient cohort with advanced endometrial carcinoma receiving lenvatinib plus pembrolizumab in an ongoing phase Ib/II study of selected solid tumors. <b>Methods:</b> Patients took lenvatinib 20 mg once daily orally plus pembrolizumab 200 mg intravenously once every 3 weeks, in 3-week cycles. The primary end point was objective response rate (ORR) at 24 weeks (ORRWk24); secondary efficacy end points included duration of response (DOR), progression-free survival (PFS), and overall survival (OS). Tumor assessments were evaluated by investigators per immune-related RECIST. <b>Results:</b> At data cutoff, 108 patients with previously treated endometrial carcinoma were enrolled, with a median follow-up of 18.7 months. The ORRWk24 was 38.0% (95% CI, 28.8% to 47.8%). Among subgroups, the ORRWk24 (95% CI) was 63.6% (30.8% to 89.1%) in patients with microsatellite instability (MSI)-high tumors (n = 11) and 36.2% (26.5% to 46.7%) in patients with microsatellite-stable tumors (n = 94). For previously treated patients, regardless of tumor MSI status, the median DOR was 21.2 months (95% CI, 7.6 months to not estimable), median PFS was 7.4 months (95% CI, 5.3 to 8.7 months), and median OS was 16.7 months (15.0 months to not estimable). Grade 3 or 4 treatment-related adverse events occurred in 83/124 (66.9%) patients. <b>Conclusion:</b> Lenvatinib plus pembrolizumab showed promising antitumor activity in patients with advanced endometrial carcinoma who have experienced disease progression after prior systemic therapy, regardless of tumor MSI status. The combination therapy had a manageable toxicity profile. <b>Trial registration:</b> ClinicalTrials.gov NCT02501096.

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