SHERLOC: A phase 2 study of MM-121 plus with docetaxel versus docetaxel alone in patients with heregulin (HRG) positive advanced non-small cell lung cancer (NSCLC).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 9036-9036 ◽  
Author(s):  
Lecia V. Sequist ◽  
Pasi A. Janne ◽  
Rudolf M. Huber ◽  
Jhanelle Elaine Gray ◽  
Enriqueta Felip ◽  
...  
Keyword(s):  
Interim Analysis ◽  
Response Rate ◽  
Objective Response ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Phase 2 ◽  
Multiple Cancer ◽  
Open Label ◽  
Eligibility Criteria ◽  
Phase 2 Study

9036 Background: Seribantumab (MM-121) is a human monoclonal IgG2 antibody that blocks the HRG domain of HER3. Preclinical data suggest that seribantumab reverses HRG mediated drug resistance across multiple cancer models. In prior retrospective analyses, addition of seribantumab to standard of care (SOC) appeared to improve outcomes in pts with HRG+ tumors. Here we tested if seribantumab plus SOC improved progression-free survival (PFS) in pts with HRG+ lung adenocarcinoma who had received prior platinum-based therapy. Methods: SHERLOC was a randomized, open-label, multicenter, Phase 2 study in pts with advanced HRG+ adenocarcinoma of the lung. Archival or pre-treatment tumor samples were assessed for HRG+ by RNA in situ hybridization. Eligibility criteria included prior platinum-based therapy for advanced disease with ≤ 2 total prior lines of therapy (prior IO was allowed) and no EGFR or ALK mutations. Pts were randomized 2:1 to receive seribantumab 3000 mg/docetaxel 75 mg IV q3w (experimental; exp) or docetaxel 75 mg IV q3w alone (control). Primary endpoint was PFS. Key secondary endpoints were overall survival (OS), objective response rate (ORR), and adverse event (AEs) profile. Results: At a pre-specified interim analysis of 75% of total PFS events, 108 pts were enrolled (exp n = 71, control n = 37). Median age was 62y (range 34-83y); female 34%; one prior treatment only 39%. Median PFS was 3.0m for exp and 4.0m for control, HR = 1.66m (p = 0.084). Median OS was 7.9m for exp and 8.4m for control, HR = 1.50 (p = 0.235). ORR was 19.7% for exp and 5.6% for control (p = 0.052). Serious AEs were more frequent in the exp arm (40.8%) vs control (24.3%). Most common treatment emergent AEs (TEAEs) in the exp arm were diarrhea (47%), fatigue (37%), and neutropenia (27%). Based on a determination of futility at interim analysis, the study was terminated early. Conclusions: Seribantumab failed to improve PFS when added to docetaxel among previously treated advanced HRG+ NSCLC pts. A higher response rate and a higher incidence of TEAEs were observed in the exp arm. No further study of seribantumab is planned in NSCLC. Clinical trial information: NCT02387216.

A phase II study of ABT-869 in hepatocellular carcinoma (HCC): Interim analysis

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4581-4581 ◽  
Author(s):  
H. Toh ◽  
P. Chen ◽  
B. I. Carr ◽  
J. J. Knox ◽  
S. Gill ◽  
...  
Keyword(s):  
Growth Factor ◽  
Ct Scan ◽  
Phase Ii ◽  
Tyrosine Kinases ◽  
Interim Analysis ◽  
Objective Response ◽  
Progression Free Survival ◽  
Open Label ◽  
Eligibility Criteria ◽  
Phase 2 Trial

4581 Background: ABT-869 is a novel orally active, potent and selective inhibitor of the vascular endothelial growth factor and platelet derived growth factor families of receptor tyrosine kinases. Results of an interim analysis of a phase 2 trial of ABT-869 in HCC are presented. Methods: An open-label, multicenter phase II trial (M06–879) of oral ABT-869 at 0.25 mg/kg daily in Child-Pugh A (C-PA) or QOD in Child-Pugh B (C-PB) patients (pts) until progressive disease (PD) or intolerable toxicity, is ongoing. Key eligibility criteria included unresectable or metastatic HCC; up to one prior line of systemic treatment; and at least one measurable lesion by computed tomography (CT) scan. The primary endpoint was the progression free (PF) rate at 16 weeks. Secondary endpoints included objective response rate (ORR), time to progression (TTP), progression free survival (PFS) and overall survival (OS). CT scans were assessed centrally and by the investigators; presented results are from central assessment. Results: 44 pts were enrolled from 09/07 to 08/08 at 6 centers internationally, with interim data available for 34 pts. There were 28 C-PA pts (median age, 63.5 y [range, 20- 81]) and 6 C-PB pts (median age, 64.5 y [range, 36–69]) and 73.5% received no prior systemic therapy. For the 19 evaluable C-PA pts included in the per-protocol interim analysis, 8 (42.1%) were progression free at 16 weeks [95% CI 20.3, 66.5]. The estimated ORR was 8.7% [95% CI, 1.1, 28] for the 23 C-PA pts and 0% for the 2 C-PB pts who had at least one post-baseline CT scan reviewed by central imaging. For all 34 pts, median TTP was 112 d [95% CI, 110, -], median PFS was 112 d [95% CI, 61, 168] and median OS was 295 d [95% CI, 182, 333]. The most common adverse events (AEs) for all pts were hypertension (41%), fatigue (47%), diarrhea (38%), rash (35%), proteinuria (24%), vomiting (24%), cough (24%) and oedema peripheral (24%). The most common grade 3/4 AEs for all pts were hypertension (20.6%) and fatigue (11.8%). Most AEs were mild/moderate and reversible with interruption/dose reductions/or discontinuation of ABT-869. Conclusions: ABT-869 appears to benefit HCC patients, with an estimated TTP of 112 days and an acceptable safety profile. Updated results from this ongoing study will be presented. [Table: see text]

FIGHT-205: Phase II study of first-line pemigatinib (PEMI) plus pembrolizumab (PEMBRO) versus PEMI alone versus standard of care (SOC) for cisplatin (CIS)—Ineligible urothelial carcinoma (UC) with FGFR3 mutation or rearrangement.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. TPS592-TPS592
Author(s):  
Matt D. Galsky ◽  
Thomas Powles ◽  
Robert Dreicer ◽  
Hiroshi Kitamura ◽  
Ekatherine Asatiani ◽  
...  
Keyword(s):  
Objective Response ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Cell Receptor ◽  
Target Lesion ◽  
Ectopic Calcification ◽  
Phase 2 ◽  
Open Label ◽  
Fgfr3 Mutation

TPS592 Background: Fibroblast growth factor receptor (FGFR) 3 gene alterations (GAs) are involved in UC pathogenesis. Pts with metastatic UC and FGFR3 GAs express low programmed cell death ligand 1 (PD-L1) levels; combination with FGFR inhibitors may confer added benefit via tumor-direct and immunomodulatory effects. Preliminary data from a phase 2 monotherapy trial of PEMI (INCB054828), a selective, potent, oral FGFR1–3 inhibitor, confirmed efficacy in previously treated relapsed/refractory pts with UC and FGFR3 GAs (NCT02872714). FIGHT-205, a randomized, open-label, phase 2 study, will assess efficacy and safety of PEMI + PEMBRO vs PEMI alone vs SOC (carboplatin [CARB] + gemcitabine [GEM] or PEMBRO alone) in CIS-ineligible metastatic/unresectable UC with FGFR3 mutation/rearrangement (NCT04003610). Methods: Eligible pts are adults with confirmed metastatic/unresectable UC; ≥1 measurable target lesion (per RECIST v1.1); platinum (PT)/CIS-ineligible; centrally confirmed FGFR3 mutation/rearrangement; ECOG PS ≤2. Exclusions include prior selective FGFR inhibitor, anti-PD-1/PD-L1/2, or co-inhibitory T-cell receptor directed agent; chemotherapy (except adjuvant, neoadjuvant); clinically significant corneal/retinal disorder; Ca/PO4 homeostasis disorder/systemic mineral imbalance with ectopic calcification; untreated CNS metastases. Pts will be randomized (1:1:1) to 3 groups: PEMI 13.5 mg QD (continuous, 21-d cycle) + PEMBRO 200 mg Q3W, PEMI alone (same dose), or SOC (GEM [1000 mg/m2 on D1 + D8] + CARB [AUC 5 (or 4.5) on D1 or D2] Q3W or PEMBRO [same dose] if PD-L1 score high/PT-ineligible). PEMI titration to 18 mg starting at cycle 2 is required for pts without hyperphosphatemia (serum PO4 >5.5 mg/dL) and grade ≥2 treatment-related AEs during cycle 1. Hyperphosphatemia will be managed by diet modifications, PO4 binders, diuretics, or dose adjustments. PEMI will continue until progression/unacceptable toxicity. Primary endpoint is progression-free survival. Secondary endpoints are overall survival, objective response rate, duration of response, safety, and quality of life. Clinical trial information: NCT04003610.

Phase 2, two-group, two-stage study of avelumab in patients (pts) with microsatellite stable (MSS), microsatellite instable (MSI), and polymerase epsilon (POLE) mutated recurrent/persistent endometrial cancer (EC).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 5502-5502 ◽  
Author(s):  
Panagiotis A. Konstantinopoulos ◽  
Joyce F. Liu ◽  
Weixiu Luo ◽  
Carolyn N. Krasner ◽  
Jeffrey Joseph Ishizuka ◽  
...  
Keyword(s):  
Objective Response ◽  
Progression Free Survival ◽  
Phase 2 ◽  
Eligibility Criteria ◽  
Prior Therapy ◽  
Primary Endpoints ◽  
Phase 2 Study ◽  
Heavily Pretreated ◽  
Pretreated Patients ◽  
Mmr Proteins

5502 Background: This non-randomized phase 2 study evaluated the PD-L1 inhibitor avelumab in two cohorts of EC: i) MSI/ POLE cohort including ECs with immunohistochemical (IHC) loss of expression of at least one of the mismatch repair (MMR) proteins and/or documented mutation in the exonuclease domain of POLE and ii) MSS cohort including ECs with normal IHC expression of all MMR proteins. Methods: Eligibility criteria included measurable disease, unlimited prior therapies, and any EC histology. Co-primary endpoints were confirmed objective response (OR) and progression-free survival rate at 6 months (PFS6). Avelumab 10 mg/kg IV was given every 2 weeks until progression or unacceptable toxicity. In the 1st stage, 16 pts were enrolled in each cohort; if there were ≥2 ORs or ≥2 PFS6 responses, accrual would continue to the 2nd stage with enrollment of 19 additional pts. Overall, if there are ≥4 ORs or ≥8 PFS6 responses, avelumab would be considered worthy of further study in each cohort. Results: As of 12/2018, 33 pts were enrolled. The MSS cohort was closed at the 1st stage due to futility; of 16 pts in the MSS cohort, only 1 pt exhibited an OR and PFS6 response [ORR and PFS6 rate 6.25% (95% CI 0.16%-30.2%)]. Conversely, the MSI/POLE cohort reached the primary endpoint of 4 ORs after accrual of only 17 pts. Two pts in the MSI/POLE cohort did not initiate protocol therapy and were excluded from all analyses. Of 15 pts in the MSI/POLE cohort, 4 pts exhibited OR [1CR+3PRs, OR rate (ORR) 26.7% (95% CI 7.8%-55.1%)] and 6 pts (including the 4 pts with OR) exhibited PFS6 responses [PFS6 rate 40.0% (95% CI 16.3%-66.7%)], 4 ongoing and 3 approaching 2 yrs. Twenty-two pts (71%) reported treatment related toxicities, 6 patients (19%) G3 toxicities; there were no treatment-related G4 and G5 toxicities. In the MSI/POLE cohort, 5 of 6 PFS6 responses were observed in pts with ≥3 lines of prior therapy (p = 0.011) and in tumors who were PD-L1 negative by IHC. Further correlative work will be reported at the meeting. Conclusions: In EC pts stratified by MSI/POLE status, MSI vs MSS status appears to be correlated with avelumab response even in PD-L1 negative tumors. Responses in the MSI/POLE cohort were more frequent in more heavily pretreated patients, a finding that warrants further investigation. Clinical trial information: NCT02912572.

scholarly journals A phase 2 study of trametinib for patients with pediatric glioma or plexiform neurofibroma with refractory tumor and activation of the MAPK/ERK pathway: TRAM-01

BMC Cancer ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Sébastien Perreault ◽  
Valérie Larouche ◽  
Uri Tabori ◽  
Cynthia Hawkin ◽  
Sarah Lippé ◽  
...  
Keyword(s):  
Single Agent ◽  
Objective Response ◽  
Plexiform Neurofibroma ◽  
Progression Free Survival ◽  
Primary Objective ◽  
Low Grade ◽  
Erk Pathway ◽  
Phase 2 ◽  
Open Label ◽  
Phase 2 Study

Abstract Background Pediatric low-grade gliomas (PLGG) are the most frequent brain tumors in children. Up to 50% will be refractory to conventional chemotherapy. It is now known that the majority of PLGG have activation of the MAPK/ERK pathway. The same pathway is also activated in plexiform neurofibromas (PNs) which are low-grade tumors involving peripheral nerves in patients with neurofibromatosis type 1 (NF1). These lesions are known to be refractory to chemotherapy. Specific MEK inhibitors such as trametinib are now available and have been approved for other cancers harboring mutations in the MAPK/ERK pathway such as melanoma. We have observed significant responses to trametinib in patients with refractory PLGG in our institutions and results from the phase I study are promising. The treatment appears not only efficacious but is also usually well tolerated. We hypothesize that we will observe responses in the majority of refractory PLGG and PN treated with trametinib in this phase 2 study. Methods The primary objective is to determine the objective response rate of trametinib as a single agent for treatment of progressing/refractory tumors with MAPK/ERK pathway activation. The TRAM-01 study is a phase II multicentric open-label basket trial including four groups. Group 1 includes NF1 patients with progressing/refractory glioma. Group 2 includes NF1 patients with plexiform neurofibroma. Group 3 includes patients with progressing/refractory glioma with KIAA1549-BRAF fusion. Group 4 includes other patients with progressing/refractory glioma with activation of the MAPK/ERK pathway. Eligible patients for a given study group will receive daily oral trametinib at full dose for a total of 18 cycles of 28 days. A total of 150 patients will be enrolled in seven Canadian centers. Secondary objectives include the assessment of progression-free survival, overall survival, safety and tolerability of trametinib, serum levels of trametinib and evaluation of quality of life during treatment. Discussion Trametinib will allow us to target directly and specifically the MAPK/ERK pathway. We expect to observe a significant response in most patients. Following our study, trametinib could be integrated into standard treatment of PLGG and PN. Trial registration ClinicalTrials.gov Identifier: NCT03363217 December 6, 2017.

Phase II study of zolbetuximab plus pembrolizumab in claudin 18.2: Positive locally advanced or metastatic gastric or gastroesophageal junction adenocarcinoma (G/GEJ)—ILUSTRO Cohort 3.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. TPS260-TPS260
Author(s):  
Samuel J Klempner ◽  
Jaffer A. Ajani ◽  
Salah-Eddin Al-Batran ◽  
Yung-Jue Bang ◽  
Daniel V.T. Catenacci ◽  
...  
Keyword(s):  
Performance Status ◽  
Gastroesophageal Junction ◽  
Objective Response ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Phase 2 ◽  
Open Label ◽  
Eligibility Criteria ◽  
Gastroesophageal Junction Adenocarcinoma ◽  
Junction Protein

TPS260 Background: Five-year survival with advanced G/GEJ is poor, and limited biomarkers exist to inform optimal treatment selection. Pembrolizumab, an anti–programmed death-1 receptor (PD-1) antibody, is approved for advanced/metastatic PD-ligand 1–positive (PD-L1+) G/GEJ that progressed after ≥2 lines of therapy. The transmembrane tight junction protein claudin 18.2 (CLDN18.2) is normally confined to gastric mucosa but is often overexpressed in G/GEJ with roughly one-third of patients (pts) having high expression (≥75%). Zolbetuximab, a chimeric IgG1 monoclonal antibody, binds to CLDN18.2 and mediates cancer cell death through antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity. Phase 2 (NCT01630083) results showed prolonged survival with zolbetuximab + epirubicin, oxaliplatin, and capecitabine (EOX) vs EOX alone in G/GEJ. Results of nonclinical studies showed enhanced antitumor activity with zolbetuximab + anti-murine PD-1 antibody, and it was hypothesized that a combination with pembrolizumab (new Cohort 3) might augment ADCC and antitumor immune response in CLDN18.2 overexpressing G/GEJ. Methods: This phase 2 open-label study (NCT03505320) will enroll ~112 adult pts from 22 sites in 5 countries into 3 cohorts; this abstract describes Cohort 3 (~62 pts). Key eligibility criteria are advanced/metastatic G/GEJ, measurable disease (RECIST v1.1), adequate organ function and performance status, and high/intermediate (Cohort 3A) or high (Cohort 3B) expression of CLDN18.2. Central testing of tumor tissue will determine CLDN18.2 expression; pts are considered CLDN18.2 positive (CLDN18.2+) if ≥75% (high) or ≥50% to < 75% (intermediate) of tumor cells demonstrate moderate-to-strong membranous IHC staining. Patients in Cohort 3B are required to be PD-L1+, defined as a combined positive score ≥1 (IHC staining per the Dako 22C3 PD-L1 assay). Patients will receive zolbetuximab + pembrolizumab in the third/later line in Cohort 3A and third line in Cohort 3B. In Cohort 3A (safety cohort), zolbetuximab will be administered at a loading dose of 800 mg/m2 IV on Day 1 Cycle 1 followed by 600 mg/m2 IV every 3 weeks; a reduction from 600 mg/m2 every 3 weeks is permitted. Pembrolizumab 200 mg IV will be administered on Day 1 of each 21-day cycle. Cohort 3B (expansion cohort) zolbetuximab dose is determined from results of Cohort 3A. Imaging will occur every 6 weeks for 24 weeks and every 12 weeks thereafter. The primary endpoint is objective response rate; additional endpoints include duration of response, disease control rate, and progression-free survival by independent review committee and investigator assessment. Pharmacokinetics, safety/tolerability, quality of life, and immunogenicity will be assessed. The study is currently recruiting pts. Clinical trial information: NCT03505320.

scholarly journals MON-521 An Open-Label, Single-Arm, Multicenter, Phase 2 Trial of Lenvatinib (LEN) for the Treatment of Anaplastic Thyroid Cancer (ATC)

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Lori J Wirth ◽  
Marcia S Brose ◽  
Eric J Sherman ◽  
Soamnauth Misir ◽  
Sharon Xie ◽  
...  
Keyword(s):  
Interim Analysis ◽  
Objective Response ◽  
Progression Free Survival ◽  
Phase 2 ◽  
Bleeding Events ◽  
Braf Mutations ◽  
Open Label ◽  
Histologic Diagnosis ◽  
Systemic Treatments ◽  
Grade 3

Abstract Background: ATC is aggressive, with a low 5-year patient (pt)-survival rate. Apart from recent advances in treating ATCs in pts with BRAF mutations, systemic treatments have limited efficacy and duration of response is short. In a small, phase 2 study conducted in Japan, 24% of pts with ATC achieved a partial response (PR) with LEN (Study 208 [Takahashi, Future Oncol. 2019]). This study (NCT02657369 [Study 213]) aimed to further evaluate the efficacy and safety of LEN in a broader population of pts with ATC. Methods: Study 213 was performed in collaboration with the International Thyroid Oncology Group and enrolled pts with ATC to receive LEN 24 mg/day. Key inclusion criteria were: histologic diagnosis of ATC, measurable disease per RECIST v1.1, ECOG score ≤1, and adequate organ function. Previous surgery, radiation, and neoadjuvant, adjuvant, or palliative chemotherapy for ATC were allowed. The primary end point (confirmed objective response rate [ORR]) was determined by investigator review per RECIST v1.1. Interim analysis was done after the first 20 evaluable pts completed ≥2 tumor assessments (baseline and 6-week scan) or discontinued treatment. Results: The study was halted for futility when the minimum threshold for ORR (15%) was not met at the interim analysis. The full analysis set (FAS) included 34 pts because the protocol allowed enrollment until the interim analysis was complete. The median pt age was 66.5 years old and most were female (n=21/34), white (n=27/34), and had been treated with 1 or 2 prior anticancer regimens (n=20/34). Unconfirmed PR was experienced in 1/20 pts (ORR 5%; 95% CI 0.1–24.9%) in the interim analysis set. In the FAS, 1/34 pts had a confirmed PR (cPR) (ORR 3%; 95% CI 0.1–15.8%). In the interim and FAS, median progression-free survival (2.6 and 2.6 months, respectively) and median OS (2.9 and 3.2 months, respectively) were similar. In addition to the 1 cPR, 7 pts had 22–63% shrinkage in tumor measurements but did not meet the response criteria (FAS). Grade 3/4 treatment-emergent (TE) adverse events (AEs) occurred in 82.4% of pts, and 61.8% of pts experienced grade 3/4 treatment-related AEs (FAS). Grade 5 TEAEs occurred in 14/34 pts and there were 27 deaths by the time of data cut-off. There were no treatment-related deaths, and no major treatment-related bleeding events occurred. Conclusion: In contrast to Study 208, Study 213 enrolled more pts with ATC (34 vs 17), more of whom had received prior chemotherapy (62% vs 41%). Additionally, in Study 208, all pts were Japanese and tumor assessments were conducted more frequently (4- vs 6-weekly). These differences may have contributed to the observed variation in results between the 2 studies. AEs observed were consistent with the safety profile of LEN or with ATC. Further investigation of LEN in combination with a checkpoint inhibitor may be warranted.

428 Interim analysis of Phase 2 results for cemiplimab in patients with metastatic basal cell carcinoma (mBCC) who progressed on or are intolerant to hedgehog inhibitors (HHIs)

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A453-A453
Author(s):  
Karl Lewis ◽  
Ketty Peris ◽  
Aleksandar Sekulic ◽  
Alexander Stratigos ◽  
Lara Dunn ◽  
...  
Keyword(s):  
Cell Carcinoma ◽  
Interim Analysis ◽  
Objective Response ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Good Clinical Practice ◽  
Phase 2 ◽  
Curative Surgery ◽  
Pivotal Phase ◽  
Study Protocols

BackgroundHHIs, vismodegib and sonidegib, are approved for treatment of patients with mBCC or locally advanced BCC who are not candidates for surgery or radiation. There is no approved option for patients who progress on or are intolerant to HHIs. Cemiplimab is an anti-programmed cell death-1 monoclonal antibody approved for treatment of patients with metastatic cutaneous squamous cell carcinoma (CSCC) or locally advanced CSCC who are not candidates for curative surgery or curative radiation. Here we present the prespecified interim analysis of the mBCC cohort from the pivotal Phase 2, non-randomized, multi-center study of cemiplimab in patients with advanced BCC who discontinued HHI therapy due to disease progression, intolerance, or no better than stable disease after 9 months (NCT03132636).MethodsPatients with mBCC (nodal and/or distant) received cemiplimab 350 mg intravenously every 3 weeks; interim analysis included patients with the opportunity to be followed for approximately 57 weeks. The primary endpoint was objective response rate (ORR) per independent central review (ICR). Secondary objectives included assessment of safety and tolerability, estimation of duration of response (DOR), progression-free survival (PFS), and overall survival (OS).ResultsIn this interim efficacy analysis of 28 patients, 82.1% were males and median age was 65.5 years (range 38−90). Six patients had a partial response, per ICR, for an ORR of 21.4% (95% CI, 8.3, 41.0). ORR per investigator assessment was 28.6% (95% CI, 13.2, 48.7). Among responders, observed DOR was 9−23 months. Median time to response per ICR was 3.2 months (range, 2.1−10.5). Median Kaplan–Meier (KM) estimation of PFS was 8.3 months. Median DOR had not been reached and median KM estimation of OS was 25.7 months. All six responses had observed durations of at least 8 months. The disease control rate was 67.9% (95% CI, 47.6, 84.1).The most common treatment emergent adverse events (TEAEs) regardless of attribution were fatigue (50.0%), diarrhea (35.7%), pruritus (25.0%), and constipation (25.0%). Hypertension (n=2) was the only Grade ≥3 TEAE regardless of attribution occurring in ≥2 patients. TEAEs leading to death occurred in one (3.6%) patient who died from staphylococcal pneumonia, considered unrelated to study treatment.ConclusionsThis interim analysis demonstrates that cemiplimab is the first agent to provide clinically meaningful anti-tumor activity, including durable responses, in patients with mBCC after progression or intolerance on HHI therapy.AcknowledgementsEditorial acknowledgment: Medical writing support was provided by Cindi Hoover, PhD of Prime, Knutsford, UK, funded by Regeneron Pharmaceuticals, Inc. and Sanofi.Ethics ApprovalThe study protocols and all amendments were approved by the institutional review board at each participating study site. The study was conducted in accordance with the principles of the Declaration of Helsinki and with Good Clinical Practice guidelines as defined by the International Conference on Harmonization. All patients provided written informed consent before enrollment.

Atezolizumab in combination with bevacizumab in patients with unresectable locally advanced or metastatic mucosal melanoma: Interim analysis of an open-label phase II trial.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 9511-9511
Author(s):  
Lu Si ◽  
Meiyu Fang ◽  
Yu Chen ◽  
Lili Mao ◽  
Peng Zhang ◽  
...  
Keyword(s):  
Interim Analysis ◽  
Objective Response ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Mucosal Melanoma ◽  
Stage I ◽  
Efficacy Evaluation ◽  
Open Label ◽  
Full Analysis ◽  
Ecog Ps

9511 Background: Mucosal melanoma is a rare malignant melanoma in Caucasians but ranks the second most common subtype in the Asian population. It is more often diagnosed at an advanced stage and responds poorly to current PD-1/PD-L1 inhibitors. Here we report the interim analysis results of ML41186, an open-label, multicenter, single-arm phase II study, aiming to evaluate the efficacy and safety of atezolizumab in combination with bevacizumab in patients (pts) with advanced mucosal melanoma. Methods: Eligible pts aged 18 to 75 years with histologically confirmed unresectable locally advanced or metastatic mucosal melanoma had at least one measurable lesion per RECIST version 1.1 at baseline, with an ECOG PS 0 or 1 and adequate hematologic and organ function. ML41186 is a Simon two-stage design study, if 22 pts completed ORR evaluation and more than 3 pts respond in stage I, the study then continue to Stage II. Atezolizumab and bevacizumab were administered at a fixed dose of 1200 mg and 7.5 mg/kg Q3W respectively (on day 1 of each 21-day cycle) until unacceptable toxicity or loss of clinical benefit. The primary endpoint is the objective response rate (ORR). The secondary endpoints include progression-free survival (PFS), duration of objective response (DoR), disease control rate (DCR), and safety. Results: By the cut-off date of 9th September 2020, 35 pts has been enrolled, among whom 22 pts in the stage I analysis set has completed two efficacy evaluation, while 28 pts (full analysis set) has completed at least one efficacy evaluation. In ITT populations (n=35), mean age was 58.9 years with 10 (28%) pts had ECOG PS of 1. LDH level elevated in 9 (25.7%) pts. More than half pts (19, 54.3%) had metastatic mucosal melanoma, of whom 3 (15.8%) pts had more than 3 metastasis sites and 4 (21.1%) pts had liver metastasis. In stage I analysis set (n=22), the best confirmed ORR was 36.4% (95% CI, 17.0%-59.3%). Median progression-free survival was 5.32 months (95% CI, 1.58-not reached), and the best confirmed DCR was 59.1% (95%CI, 36.4%-79.3%). The median confirmed DoR was not reached (95% CI, 2.76-NR). In the full analysis set (n=28), the unconfirmed ORR was 42.9% (95%CI, 24.5%-62.8%). In ITT populations (n=35), 28 pts (80%) experienced at least one adverse event (AE) and 5 pts (14.3%) experienced at least one grade 3-4 AEs. Only one patient experienced AE leading to treatment discontinuation. One patient died of autoimmune lung disease. Conclusions: The combination of atezolizumab plus bevacizumab showed promising benefit and was tolerable in pts with advanced mucosal melanoma. At the time of this interim analysis, the primary endpoint did not cross the futility boundary, thus the study will run into Stage II. Clinical trial information: NCT04091217.

scholarly journals Phase 3 Study of Pomalidomide with Cyclophosphamide and Dexamethasone Versus Pomalidomide and Dexamethasone in Asian Patients with Relapsed/Refractory Myeloma (RRMM) - Interim Analysis of a Trial By the Asian Myeloma Network (AMN)

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 1-1
Author(s):  
Wee-Joo Chng ◽  
Xinhua Li ◽  
Cindy Lin ◽  
Jin Seok Kim ◽  
Hiroshi Handa ◽  
...  
Keyword(s):  
Interim Analysis ◽  
Research Funding ◽  
Response Rate ◽  
Prior Exposure ◽  
Phase 2 ◽  
Asian Patients ◽  
Phase 2 Study ◽  
Grade 3 ◽  
Experienced Grade

Background Pomalidomide is an immunomodulatory drug that has been approved for the treatment of relapse refractory myeloma. A previous small randomized phase 2 study in the United States showed that combination of Pomalidomide, cyclophosphamide and dexamethasone induce a greater response rate than pomalidomide and dexamethasone1. In our prior study, AMN0012, we should that in patients with sub-optimal response to pomalidomide and dexamethasone, the addition of cyclophosphamide can increase response resulting in improvement of progression free survival. In the current study, we seek to randomize Asian patients with RRMM between PCD and PD to confirm the benefit of PCD. Method We conducted a prospective randomized trial of pomalidomide (4mg daily for 21 days followed by 7 days rest) plus dexamethasone 40mg once weekly for 4 weeks with or without cyclophosphamide (400mg once a week) in patients with relapse and refractory myeloma that has to be refractory to lenalidomide and has prior exposure to proteasome inhibitors. Each cycle is 4 weeks. Patients from Singapore, Japan and Korea (NCT03143049) were included in this Asian Myeloma Network trial. The trial was started in Sep 2017 and is still ongoing. To date, 53 patients have been recruited so far. This interim report presents data available up till the data cut-off date of 24 June 2020. Results Forty-six patients have available base line information and safety data and is included in this interim analysis. 50% of patients are male and median age of the cohort is 68 years old. 39% and 28% of patients are International Stage System (ISS) stage 2 and 3 respectively. 20% of patients have abnormal creatinine clearance. Median prior line of treatment is 3. All patients are refractory to lenalidomide and 96% have prior exposure to bortezomib. In addition, 12 patients (26%) and 5 (11%) have been treated with Carfilzomib and Ixazomib respectively. 15 (33%) patients had prior high dose melphalan and autologous stem cell transplant. 20 (44%) patients required dose reduction of pomalidomide, cyclophosphamide or dexamethasone. 89% of patients experience adverse events (AEs) of any grade. Of the 297 episodes of AEs, 43% are grade 3 or higher, with 50% of these episodes related to the study drugs. 57% of patients experienced serious AEs (SAEs) of any grade. Of the 74 episodes of SAE, 89% are grade 3 or higher, with 49% of these episodes related to the study drugs. Almost all of these events are related to cytopenias and infections. 20 (44%) of the patients develop grade 3 neutropenic fever and 9 (20%) patients have grade 3 or higher pneumonia. Only 1 patient experienced grade 3 peripheral neuropathy, 1 patient develop grade 3 pulmonary embolism, 1 patient developed grade 3 venous thromboembolism, and 1 patient experienced grade 3 renal impairment. At a median follow-up of 10.9 months, 9 of the 46 patients have died, and 21 have progressed. Three patients withdrew due to toxicity. While the overall response of the study population is not part of this interim analysis, we assessed the response of patients from the National University Cancer Institute, Singapore which has the highest number of patients recruited to get an idea of the therapeutic efficacy. Of the 14 patients recruited at NCIS, 1 patient achieved CR, 3 VGPR, 7 PR, producing a response rate of 79%. Conclusion In this interim analysis of a prospective randomized study of pomalidomide and dexamethasone with or without cyclophosphamide in Asian patients, we demonstrated the feasibility and efficacy of this combination. Longer follow-up and final analysis of the study will be needed to ascertain the therapeutic advantage of PCD over PD in relapse and refractory myeloma that is refractory to lenalidomide. References 1. Baz RC, Martin TG 3rd, Lin HY, Zhao X, Shain KH, Cho HJ, Wolf JL, Mahindra A, Chari A, Sullivan DM, Nardelli LA, Lau K, Alsina M, Jagannath S. Randomized multicenter phase 2 study of pomalidomide, cyclophosphamide, and dexamethasone in relapsed refractory myeloma. Blood. 2016 May 26;127(21):2561-8. 2. Soekojo CY, Kim K, Huang SY, Chim CS, Takezako N, Asaoku H, Kimura H, Kosugi H, Sakamoto J, Gopalakrishnan SK, Nagarajan C, Wei Y, Moorakonda R, Lee SL, Lee JJ, Yoon SS, Kim JS, Min CK, Lee JH, Durie B,Chng WJ. 3. Pomalidomide and dexamethasone combination with additional cyclophosphamide in relapsed/refractory multiple myeloma (AMN001)-a trial by the Asian Myeloma Network. Blood Cancer J. 2019 Oct 8;9(10):83. Disclosures Chng: Novartis: Honoraria; Abbvie: Honoraria; Amgen: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Celgene: Honoraria, Research Funding. Kim:Alexion Pharmaceuticals Inc.: Honoraria, Research Funding. Durie:Amgen, Celgene, Johnson & Johnson, and Takeda: Consultancy.

A phase 2 study of pamiparib in the treatment of patients with locally advanced or metastatic HER2-negative breast cancer with germline BRCA mutation.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 1087-1087
Author(s):  
Tao Sun ◽  
Yanxia Shi ◽  
Jiuwei Cui ◽  
Yongmei Yin ◽  
Quchang Ouyang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Brca Mutation ◽  
Objective Response ◽  
Locally Advanced ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Phase 2 ◽  
Open Label ◽  
Hormone Receptor Positive ◽  
Her2 Breast Cancer

1087 Background: Breast cancer is the most common cancer among women, with up to 37% of patients (pts) harboring germline BRCA1/2 mutations (g BRCA1/2m) that appear to be sensitive to poly (ADP-ribose) polymerase proteins 1 and 2 (PARP1/2) inhibition. Pamiparib is an orally administered selective PARP1/2 inhibitor that has the potential to cross the blood-brain barrier. This study evaluated the efficacy and safety of pamiparib in pts with locally advanced/metastatic human epidermal growth factor receptor 2-negative (HER2-) breast cancer, with deleterious or suspected deleterious g BRCA1/2m, who received ≤ 2 prior lines of chemotherapy. Methods: In this open-label, phase 2, multi-center study in China (NCT03575065), pts with locally advanced/metastatic HER2- breast cancer with deleterious or suspected deleterious g BRCA1/2m triple negative breast cancer (TNBC cohort) or hormone receptor-positive (HR+)/HER2- breast cancer (HR+ cohort) were enrolled. Pts received pamiparib 60 mg orally twice daily in 28-day cycles. The primary endpoint was objective response rate (ORR; RECIST v1.1) by independent review committee (IRC). Secondary endpoints included duration of response (DOR) and progression free survival (PFS) by IRC, overall survival (OS), safety and tolerability. Results: 88 pts were enrolled (median age 45.5 years), 76 pts (TNBC cohort n = 55; HR+ cohort n = 21) had measurable disease at baseline per IRC. 60 pts (68.2%) received 1 or 2 prior lines of chemotherapy; 42 pts (47.7%) were treated with platinum previously. Median follow-up was 13.77 months (TNBC cohort, 10.87 months; HR+ cohort, 18.45 months). In the TNBC cohort: confirmed ORR was 38.2% (95% CI: 25.4–52.3); median DOR (mDOR) was 6.97 months (95% CI: 3.94–not estimable[NE]); median PFS (mPFS) was 5.49 months (95% CI: 3.65–7.33); median OS (mOS) was 17.08 months (95% CI:13.70–NE). In the HR+ cohort: confirmed ORR was 61.9% (95% CI: 38.4–81.9); mDOR was 7.49 months (95% CI: 5.55–14.75); mPFS was 9.20 months (95% CI: 7.39–11.93); mOS was not reached (NR; 95% CI 18.10–NE). ≥ Grade 3 treatment emergent adverse events (TEAEs) occurred in 54 pts (61.4%); anemia was the most common TEAE, occurring in 77 pts (87.5%). Dose reduction due to TEAEs occurred for 57 pts (64.8%); discontinuations due to TEAEs occurred for 2 pts (2.3%). Conclusions: Pamiparib showed a promising response in pts with locally advanced/metastatic HER2- breast cancer with a g BRCA1/2m. The safety profile of pamiparib was considered acceptable and was generally consistent with therapies in the same class. Clinical trial information: NCT03575065 .[Table: see text]

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