Interim results of a phase 1b/2a study evaluating the nano pharmaceutical CRLX101 with bevacizumab (bev) in the treatment of patients (pts) with refractory metastatic renal cell carcinoma (mRCC).

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 412-412 ◽  
Author(s):  
Stephen Michael Keefe ◽  
Daniel Heitjan ◽  
Meliessa Hennessey ◽  
Janelle Robinson ◽  
Kristine Mykulowicz ◽  
...  
Keyword(s):  
Clear Cell ◽  
Single Agent ◽  
Progression Free Survival ◽  
Free Survival ◽  
Antiangiogenic Therapies ◽  
Clinical Models ◽  
Phase 1B ◽  
Dual Inhibition ◽  
Grade 3 ◽  
Clinical Trial Information

412 Background: VHL is inactivated in most clear cell RCC (ccRCC) tumors giving rise to the HIF hypoxia response program and tumor angiogenesis. Antiangiogenic therapies are active in ccRCC, but resistance develops in all pts. Dual inhibition strategies may be needed to overcome resistance. CRLX101, a novel nano pharmaceutical formulation of camptothecin, has been shown in pre-clinical models to target HIF. We combined CRLX101 with bev in the treatment of pts with refractory mRCC in order to determine the safety and the recommended phase 2 dose (RP2D) of the combination, and to determine the therapeutic activity of treatment. Methods: Pts with mRCC refractory to conventional antiangiogenic therapies (all subtypes) were treated every 2 weeks with bev 10 mg/kg and escalating doses of CRLX101 (12 mg/m2, 15 mg/m2) in a standard 3+3 design with an expansion at the RP2D. Pts were treated until progression, death, or prohibitive toxicity. Adverse events were classified using CTCAE v 4.0. Radiographic results were assessed by RECIST v1.1. Results: 10 pts were enrolled on study – 6 clear cell, 2 papillary, 2 chromophobe. Median prior number of therapies was 2. No dose limiting toxicities were observed. CRLX101 at its single-agent RP2D (15 mg/m2) was safely combined with standard bev. 2 episodes of grade 3 non-infectious cystitis and 1 episode of grade 3 hypertension were observed. All other toxicities were grade 1 or 2. The median progression free survival (PFS) was 7.6 months which exceeded our pre-specified threshold of 16 weeks and has triggered 2nd stage accrual. 3 of 9 evaluable pts (33%) achieved a confirmed partial response (PR) including 1 patient with papillary mRCC; 4 pts (44%) displayed stable disease, and 2 had progressive disease as their best overall response. Conclusions: Our results demonstrate that CRLX101 can be safely combined with bev in pts with refractory mRCC. The RP2D is 15 mg/m2 q2w of CRLX101 with standard bev. Preliminary outcomes to date suggest that clinical benefit, manifest as prolonged PFS, is conferred to pts with all histologic subtypes of mRCC. Clinical trial information: NCT01625936.

A phase Ib trial of IPI-926, a hedgehog pathway inhibitor, plus gemcitabine in patients with metastatic pancreatic cancer.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 213-213 ◽  
Author(s):  
Donald Anthony Richards ◽  
Joe Stephenson ◽  
Brian M. Wolpin ◽  
Carlos Becerra ◽  
John Turner Hamm ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Single Agent ◽  
Progression Free Survival ◽  
Metastatic Pancreatic Cancer ◽  
Final Report ◽  
Double Blind ◽  
Free Survival ◽  
Phase 1B ◽  
Grade 3 ◽  
Dose Reductions

213 Background: IPI-926 is a novel, natural product-derived small molecule that targets the Hedgehog (Hh) pathway by inhibiting smoothened. In preclinical models of pancreatic cancer, repressing activation of the Hh pathway diminishes tumor-associated desmoplasia and improves chemotherapy delivery. Methods: This is the final report of the Phase 1b portion of a Phase 1b/2 trial evaluating the safety and efficacy of IPI-926 plus gemcitabine. Eligible patients (pts) with untreated metastatic pancreatic cancer and ECOG status 0-1 were administered oral IPI-926 daily (QD) for 28-day cycles, in 3 to 6 pt dose cohorts. Gemcitabine (1,000 mg/m2) was administered IV weekly for 3 weeks with 1 week off. DLTs were evaluated during Cycle 1. Results: 16 pts (median age 69 years; range 58-86) were enrolled at IPI-926 doses of 110, 130 or 160 mg QD (single agent MTD). Pts received a median of 5 cycles (1-13). Two pts remain on trial. No IPI-926-related serious AEs have been observed. One DLT of Grade 3 AST increase was observed (130 mg dose cohort) and was asymptomatic; it resolved with dose interruption, and did not recur with dose reduction. The most common AEs occurring were fatigue (75% total, 6% ≥ Grade 3), thrombocytopenia (63%, 25%), anemia (56%, 13%), nausea (50%, 0%), diarrhea (44%, 0%), vomiting (44%, 0%), peripheral edema (44%, 0%), pyrexia (44%, 0%), and AST increase (44%, 13%). Dose reductions of IPI-926 occurred in 3 (19%) pts. Dose reductions of gemcitabine occurred in 11 (69%) pts, primarily for thrombocytopenia (9 pts). One pt (6%) discontinued due to an AE (microangiopathic hemolytic anemia). Five (31%) radiographic partial responses were observed (1/3 at 110 mg, 2/6 at 130 mg, 2/7 at 160 mg). Median progression-free survival is > 7 months. 74% of pts were alive 6 months after study entry. Conclusions: IPI-926 plus gemcitabine is well tolerated in pts with untreated metastatic pancreatic cancer, with evidence of activity and no unexpected toxicity. Complete Phase 1b data, including final overall survival, will be presented. Clinical evaluation of this combination continues in the randomized, double-blind, placebo-controlled Phase 2 portion of the trial.

Results of GROC-rev salvage regimen: Gemcitabine, rituximab, and oxaliplatin chemotherapy with revlimid for relapsed/refractory aggressive non-Hodgkin lymphoma (NHL).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 7556-7556 ◽  
Author(s):  
Fernando Cabanillas ◽  
Idalia Liboy ◽  
Alexis Cruz ◽  
Pedro Gil Solivan ◽  
Noridza Rivera ◽  
...  
Keyword(s):  
Overall Response Rate ◽  
Response Rate ◽  
Single Agent ◽  
Progression Free Survival ◽  
Salvage Regimen ◽  
Free Survival ◽  
Non Hodgkin Lymphoma ◽  
Best Response ◽  
Grade 3 ◽  
Clinical Trial Information

7556 Background: Currently there is no optimal salvage regimen for relapsed/refractory NHL (R/R NHL). Prognosis of pts who fail to achieve CR to salvage therapy is dismal. We sought to improve the CR rate by adding Lenalidomide (L) to GROC (ASCO #8530, 2008). Methods: Primary endpoint was rate of conversion to CR after switch to L for pts whose best response to GROC was <CR. Secondary endpoint was progression free survival (PFS) of all pts as well as those who achieve <CR on chemotherapy and were crossed over to L.Pts who failed to achieve at least PR after GROC x2 and those who didn’t achieve CR after GROC x6, were crossed over to L 25 mg x 3 weeks q 28 days. CRs were maintained on L x 2 yrs. Results: 34 pts were enrolled of which 32 are evaluable. Median age: 61 and 56% males. Histologies included DLBCL (81%), PTCL (9%), follicular grade 3-B (9%). Stage was III-IV in 75% and median IPI=2. Best overall response rate (ORR) at any point during treatment= 19/32 (59%) and CR 13/32 (41%). ORR before crossover to L=13/32 (41%) and CR= 8/32 (25%). There were 24 who failed to achieve CR on GROC (19 who didn’t respond at all and 5 whose maximum response was PR). Of these, 21 crossed over to L and 7 (33%) responded (CR in 5, PR in 2). The fact that 5 pts attained a CR to L thus improving the CR rate from 25% to 41% after exhibiting refractoriness to GROC is noteworthy. Of the 7 responders to L, all are alive and only 1 relapsed. At 2 yrs., overall survival (OS) was 48% and PFS 35%. This compares favorably with our previous GROC study without L in which 2 yr. OS= 33% and PFS 29%. In total, 11 pts were eligible for ASCT after chemo plus L and 8 were transplanted (3 refused). Of these eight, 6 remain in CR at 11, 18, 21, 22, 52, 74 mos. At 2 yrs, PFS for transplanted pts is 73% and for those whose response to GROC before crossover to L was <CR, it is 27 mos. Toxic events included 2 neutropenic fevers, 1 MDS (34 mos. after ASCT) and 1 AML (11 mos. after ASCT). Both of these remain continuously in CR after allo SCT. Conclusions: 2 yrOS=48% and PFS=35% with GROC-Rev are the best observed with any salvage regimen we have tested. L is active as a single agent in 29% of cases whose best response to GROC was <CR. A larger study is desirable to confirm these data. Clinical trial information: NCT01307592.

Safety and efficacy of single-agent lenalidomide in patients with relapsed and refractory multiple myeloma

Blood ◽  
2009 ◽  
Vol 114 (4) ◽  
pp. 772-778 ◽  
Author(s):  
Paul Richardson ◽  
Sundar Jagannath ◽  
Mohamad Hussein ◽  
James Berenson ◽  
Seema Singhal ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Single Agent ◽  
Progression Free Survival ◽  
Prior Treatment ◽  
Once Daily ◽  
Free Survival ◽  
Refractory Multiple Myeloma ◽  
Treatment Regimens ◽  
Common Grade ◽  
Grade 3

Abstract Lenalidomide plus dexamethasone is effective for the treatment of relapsed and refractory multiple myeloma (MM); however, toxicities from dexamethasone can be dose limiting. We evaluated the efficacy and safety of lenalidomide monotherapy in patients with relapsed and refractory MM. Patients (N = 222) received lenalidomide 30 mg/day once daily (days 1-21 every 28 days) until disease progression or intolerance. Response, progression-free survival (PFS), overall survival (OS), time to progression (TTP), and safety were assessed. Overall, 67% of patients had received 3 or more prior treatment regimens. Partial response or better was reported in 26% of patients, with minimal response 18%. There was no difference between patients who had received 2 or fewer versus 3 or more prior treatment regimens (45% vs 44%, respectively). Median values for TTP, PFS, and OS were 5.2, 4.9, and 23.2 months, respectively. The most common grade 3 or 4 adverse events were neutropenia (60%), thrombocytopenia (39%), and anemia (20%), which proved manageable with dose reduction. Grade 3 or 4 febrile neutropenia occurred in 4% of patients. Lenalidomide monotherapy is active in relapsed and refractory MM with acceptable toxicities. These data support treatment with single-agent lenalidomide, as well as its use in steroid-sparing combination approaches. The study is registered at http://www.clinicaltrials.gov as NCT00065351.

scholarly journals Phase II Trial of Cetuximab With or Without Paclitaxel in Patients With Advanced Urothelial Tract Carcinoma

2012 ◽  
Vol 30 (28) ◽  
pp. 3545-3551 ◽  
Author(s):  
Yu-Ning Wong ◽  
Samuel Litwin ◽  
David Vaughn ◽  
Seth Cohen ◽  
Elizabeth R. Plimack ◽  
...  
Keyword(s):  
Phase Ii ◽  
Urothelial Cancer ◽  
Single Agent ◽  
Progression Free Survival ◽  
Salvage Chemotherapy ◽  
Free Survival ◽  
Metastatic Urothelial Cancer ◽  
Metastatic Setting ◽  
Previously Treated ◽  
Grade 3

Purpose The benefit of salvage chemotherapy is modest in metastatic urothelial cancer. We conducted a randomized, noncomparative phase II study to measure the efficacy of cetuximab with or without paclitaxel in patients with previously treated urothelial cancer. Patients and Methods Patients with metastatic urothelial cancer who received one line of chemotherapy in the perioperative or metastatic setting were randomly assigned to 4-week cycles of cetuximab 250 mg/m2 with or without paclitaxel 80 mg/m2 per week. We used early progression as an indicator of futility. Either arm would close if seven of the initial 15 patients in that arm progressed at the first disease evaluation at 8 weeks. Results We enrolled 39 evaluable patients. The single-agent cetuximab arm closed after nine of the first 11 patients progressed by 8 weeks. The combination arm completed the full accrual of 28 patients, of whom 22 patients (78.5%) had visceral disease. Twelve of 28 patients had progression-free survival greater than 16 weeks. The overall response rate was 25% (95% CI, 11% to 45%; three complete responses and four partial responses). The median progression-free survival was 16.4 weeks (95% CI, 12 to 25.1 weeks), and the median overall survival was 42 weeks (95% CI, 30.4 to 78 weeks). Treatment-related grade 3 and 4 adverse events that occurred in at least two patients were rash (six cases), fatigue (five cases), and low magnesium (three cases). Conclusion Although it had limited activity as a single agent, cetuximab appears to augment the antitumor activity of paclitaxel in previously treated urothelial cancers. The cetuximab and paclitaxel combination merits additional study to establish its role in the treatment of urothelial cancers.

GEIS 39: Phase II trial of nabpaclitaxel for the treatment of patient with multiply relapsed/refractory desmoplastic small round cell tumor (DSRCT) and Ewing sarcoma (EwS).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 11529-11529
Author(s):  
Jaume Mora ◽  
Mariona Suñol ◽  
Nadia Hindi ◽  
Alicia Castañeda ◽  
Andrés Redondo ◽  
...  
Keyword(s):  
Single Agent ◽  
Progression Free Survival ◽  
Predictive Biomarker ◽  
Free Survival ◽  
Pediatric Solid Tumors ◽  
Meaningful Activity ◽  
Common Grade ◽  
Central Pathology ◽  
Grade 3 ◽  
Further Development

11529 Background: Nab-paclitaxel (albumin-bound paclitaxel) has shown preclinical activity against pediatric solid tumors. Preclinical data in EwS PDX models suggested high activity of nab-paclitaxel in tumors expressing high-levels of SPARC. Tumoral SPARC facilitates the accumulation of albumin in the tumor and increases the effectiveness of albumin-bound paclitaxel. Nab-paclitaxel utilizes albumin to deliver paclitaxel via caveolin-mediated endocytosis which is expressed in the EwS cells surface. We hypothesized that SPARC can be a predictive biomarker for nab-paclitaxel in EwS and DSRCT that could potentially be relevant for a better design of clinical trials and personalized treatments using nab-paclitaxel. Methods: Main endpoint of GEIS-39 was the overall response rate (ORR) assessed by RECIST 1.1 criteria with centralized pathology and imaging review. Secondary objectives included safety according to the CTCAE 4.0 criteria. Patients aged ≥ 6 months and ≤ 40 years, with relapsed/refractory DSRCT were eligible after having received at least one previous poly-chemotherapy line; EwS must have received at least two standard chemotherapy lines. Prior taxane therapy was accepted. Central pathology review selected for tumors with > Grade 3 (intense and diffuse) expression of SPARC by immunohistochemistry to be eligible. Nab-paclitaxel was administered as follows: age ≥ 21 and ≤ 40 years: 125 mg/m2 days 1, 8 and 15 in cycles of 28 days; age ≥ 6 months and ≤ 20 years: 240 mg/m2 days 1, 8 and 15 in cycles of 28 days. A 30% ORR was anticipated with a sample size of 25 patients needed to test the hypothesis. Stopping rule was set at 1 response within the first 16 treated pts. If 5 or more successes were observed in 25 pts, the results of the trial will warrant further investigation. Results: Twenty-nine patients were enrolled from June 2017 until October 2019, 11 DSRCT and 18 EwS. Median age was 32 years (range 14-69), and 5 females and 24 males were included, having received a median of 3 previous systemic treatment lines. Patients received a median of 3 cycles of nab-paclitaxel (range 1-17). In the EwS cohort an ORR of 33.3% (all partial responses, median duration 2 months) and 16.7% of stabilizations were achieved. No objective responses were observed among DSRCT pts, but 27.3% of pts achieved a stabilization. Overall, median progression free survival was 2.8 months and median overall survival 12.1 months, with no significant differences between DSRCT and EwS cohorts. Most common grade 3 toxicities were neutropenia (20.7%) and diarrhea (10.3%). Conclusions: Single agent nab-paclitaxel in biomarker selected EwS patients, but not in DSRCT, provided clinically meaningful activity that deserves further development. Nab-paclitaxel had a manageable adverse event profile. Clinical trial information: 2016-002464-14.

Vinorelbine (VRB) plus gemcitabine (GEM) as first-line treatment for elderly patients (p) with advanced non-small cell lung cancer (NSCLC): Molecular correlates

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 18040-18040
Author(s):  
I. Maestu ◽  
D. Isla ◽  
P. Diz ◽  
J. Muñoz ◽  
J. Oramas ◽  
...  
Keyword(s):  
Activities Of Daily Living ◽  
Median Survival ◽  
Daily Living ◽  
Single Agent ◽  
Progression Free Survival ◽  
Stage Iiib ◽  
Primary Tumors ◽  
Free Survival ◽  
Supraclavicular Lymph Nodes ◽  
Grade 3

18040 Background: The clinical benefit of non-cisplatin doublets vs a single agent in elderly or unfit p is still controversial. The present study focuses on clinical outcome with VRB/GEM in elderly p and the role of functional status and comorbidities. Genetic predictive markers of response to VRB/GEM will also be examined in genomic and cDNA from tumor and circulating tumor DNA. Methods: 145 chemonaive p with stage IIIB (pleural effusion or supraclavicular lymph nodes)-IV or recurrent NSCLC and age > 70 years were accrued at 32 sites between April 2004 and January 2006. Treatment consisted of VRB 25 mg/m2 IV or 60–80 mg/m2 oral plus GEM 1200 mg/m2, days 1, 8 every 21 days. Activities of daily living (ADL), instrumental activities of daily living (IADL) and comorbidities were evaluated. DNA samples were collected from primary tumors for the assessment of microtubule associated protein 4 (MAP4) and from serum for the checkpoint with forkhead-associated and ring finger (CHFR) methylation. Results: Data on 130 p is available. Median age 76 years (69–83); males: 86.8%; smokers: 70.5%; PS 0–1: 83.9%; adenocarcinoma: 34.4% / squamous: 48%; stage IIIB: 22.7%, IV: 77.3%. Self-sufficiency in ADL and IADL was 77.4% and 45.2% of the p analyzed. 68% of the p had comorbidities. Median cycles: 3 (1–8). Hematological toxicities (%p): grade 3/4 neutropenia, 7.8%/4.7%; grade 3/4 thrombocytopenia, 2.3%/0.8%; grade 3 anemia, 3.1%. Efficacy in evaluable population: PR, 23.2% (95% CI, 15.1% to 32.9%); SD, 41.1%. 24 p died during the treatment period (non toxicity related) and 21 p were not evaluable. With a median follow up of 5.8 months, median survival for the whole population was 4.97 months (m), progression free survival 4.53 m, event free survival 3.43 m, 1-year survival 26.6%. Statistically significant differences in median survival were observed among subgroups: PS 0–1/2, 6.5/2.3 m (p<0.001); sex male/female, 4.5/9.7 m (p 0.027); ADL <6/=6, 3.4/7.1 m (p 0.023). Conclusions: This trial confirms that VRB/GEM is effective, presenting a favorable toxicity profile in elderly p with advanced NSCLC. Complete data on genetic markers will be presented. No significant financial relationships to disclose.

Phase II study of biweekly administration of CPT-11 and gemcitabine in chemotherapy-naive patients with metastatic pancreatic cancer in Japan.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e15150-e15150
Author(s):  
Ryoji Takada ◽  
Tatsuya Ioka ◽  
Nobuko Ishida ◽  
Takuo Yamai ◽  
Nobuyasu Fukutake ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Phase Ii ◽  
Combination Chemotherapy ◽  
Phase Ii Study ◽  
Single Agent ◽  
Progression Free Survival ◽  
Current Standard ◽  
Free Survival ◽  
Metastatic Pancreatic Adenocarcinoma ◽  
Grade 3

e15150 Background: The current standard therapies for metastatic pancreatic adenocarcinoma in Japan are the single-agent Gemcitabine (Gem) or S-1 and Gem plus erlotinib. Irinotecan (CPT-11) is one of the promising drugs for Gem-refractory PC pts. Both Irinotecan and Gem have shown activity against these diseases with different mechanisms and are non-cross-resistant with each other. Japanese pts have the different metabolism with Irinotecan rather than pts in western countries. Methods: The aim of this phase II study was to evaluate the efficacy and safety of CPT-11 and Gem in Japanese pancreatic cancer pts. Patients with MPC and PS 0-2 were enrolled in this phase II trial. CPT-11, 100mg/m (2), was administered in 90 min. and Gem, 1000mg/m (2), was administered in 30 min. soon after CPT-11 on day1. Chemotherapy was repeated biweekly. Results: From May 2002 to May 2006 40 pts, with median age of 62 (40-74) years, were enrolled in this study. The overall response rate (RR) was 15% with disease control rate of 50%. The median progression-free survival (PFS) was 4.0 months (range: 1.0-15.0 months), and median overall survival (OS) was 7.5 months (range: 3.0-24.0 months). Grade 3/4 anemia, leucopenia occurred in 26.3, 5.2% of pts. The most common non-hematologic toxities were fatigue, diarrhea, nausea/vomiting and anorexia. Grade 3 diarrhea and nausea occurred in 10.5% of pts. Conclusions: The combination chemotherapy with Gem and CPT-11 showed favorable RR as expected and the treatment was manageable in Japanese pts with MPC. We plan to evaluate this combination chemotherapy for MPC pts after progression of FOLFIRINOX in near the future. Clinical trial information: UMIN000009963.

Onset of neutropenia as an indicator of treatment response in the phase 3 RECOURSE trial of trifluridine/tipiracil (TAS-102) versus placebo in patients with metastatic colorectal cancer.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 775-775 ◽  
Author(s):  
Atsushi Ohtsu ◽  
Takayuki Yoshino ◽  
Alfredo Falcone ◽  
Rocio Garcia-Carbonero ◽  
Guillem Argiles ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Survival Benefit ◽  
Progression Free Survival ◽  
Free Survival ◽  
Initial Onset ◽  
Grade 3 ◽  
Post Hoc ◽  
First Time ◽  
Clinical Trial Information

775 Background: TAS-102 is comprised of an antineoplastic thymidine-based nucleoside analog, trifluridine (FTD), and a thymidine phosphorylase inhibitor, tipiracil. Primary results of the RECOURSE trial demonstrated a significant improvement in overall survival (OS) and progression-free survival (PFS) with TAS-102 vs placebo (pbo) in patients (pts) with metastatic colorectal cancer refractory/intolerant to standard therapies. Neutropenia is a common TAS-102–associated adverse event and it has been hypothesized to be associated with a relatively high FTD concentration in pts. Methods: RECOURSE data were analyzed post hoc for correlations between onset of neutropenia (Grade 3/4) and survival benefit. Results: Of 533 pts given TAS-102, 75 (14%) developed Grade 3/4 neutropenia in treatment cycle 1, 86 (16%) for the first time in cycle 2, and 39 (7%) for the first time in cycle ≥3. Onset of neutropenia at any cycle was associated with longer median OS and PFS compared with no neutropenia. A consistent survival benefit was observed regardless of the cycle of initial onset of neutropenia, as demonstrated by the hazard ratio (against cycle-matched pbo control groups) and corresponding median OS differences (Table). Conclusions: An association between occurrence of earliest onset of Grade 3/4 neutropenia and survival benefit was observed. The data indicate that such survival benefit occurred regardless of whether the initial onset of neutropenia occurred after cycle 1, cycle 2, or later. Further analyses are required to fully determine whether FTD pharmacokinetics correlate with TAS-102 efficacy and onset of neutropenia, and whether cycle initiation delays affect response. Clinical trial information: NCT01607957. [Table: see text]

A phase Ib study of abemaciclib in combination with pembrolizumab for patients (pts) with stage IV Kirsten rat sarcoma mutant (KRAS-mut) or squamous non-small cell lung cancer (NSCLC) (NCT02779751): Interim results.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 9562-9562
Author(s):  
Jean-Louis Pujol ◽  
Johan F. Vansteenkiste ◽  
Luis G. Paz-Ares ◽  
Vanesa Gregorc ◽  
Julien Mazieres ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Objective Response ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Cyclin Dependent Kinase ◽  
Open Label ◽  
Free Survival ◽  
Phase 1B ◽  
Clinical Trial Information ◽  
Nonsquamous Nsclc

9562 Background: Abemaciclib is an orally administered, selective small molecule cyclin-dependent kinase 4 and 6 inhibitor. In preclinical models, abemaciclib induced intratumor immune inflammation and synergized with PD-1 blockade to enhance antitumor efficacy in anti-PD-L1 refractory disease. Here, we report the safety and antitumor activity of abemaciclib plus the approved NSCLC treatment pembrolizumab in 2 cohorts for pts with nonsquamous and squamous NSCLC. Methods: Eligible pts for this nonrandomized, open-label, multicohort, phase 1b study were either chemotherapy-naive with ≥ 1% tumor cell (TC) PD-L1 staining, KRAS-mut nonsquamous NSCLC (Cohort A) or had a squamous subtype and received ≤ 1 prior platinum-containing chemotherapy regimen (Cohort B) for metastatic NSCLC. Primary endpoint was safety; secondary objectives included objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). Results: Twenty-five pts with NSCLC were enrolled in each cohort. Most pts (68%) in Cohort B had received 1 prior line of chemotherapy. Safety profiles observed in both cohorts were largely consistent with previous reports for abemaciclib and pembrolizumab monotherapy. Grades 3/4 AEs in Cohorts A and B, respectively, included ALT increase (6 pts [24%]/ 0 pts), diarrhea (3 pts [12%]/ 0 pts), neutropenia (3 pts [12%]/ 0 pts), and pneumonitis (3 pts [12%]/ 1 pt [4%]). Six pts in Cohort A (24%) and 2 pts in Cohort B (8%) had a confirmed partial response for a disease control rate (CR+PR+SD) of 52% and 64%, respectively. In Cohort A, the ORR in pts with strong (≥50% TC) PD-L1 staining (n = 13) was 31% vs. 17% in pts with weak (1-49% TC) PD-L1 expression (n = 12). Median PFS and OS were 7.6 months (95% CI: 1.6, NR) and 22.0 months (95% CI: 9.9, NR) in Cohort A and 3.3 months (95% CI: 1.4, 5.2) and 6.0 months (95% CI: 3.7, 13.1) in Cohort B, respectively. Conclusions: Abemaciclib plus pembrolizumab resulted in a numerical higher rate of transaminase elevations and pneumonitis. Antitumor activity was remarkable in the KRAS-mut nonsquamous NSCLC but not noticeably higher as compared to historical data for pembrolizumab monotherapy. Clinical trial information: NCT02779751 .

RECIST and iRECIST criteria for the evaluation of nivolumab + ipilimumab combination in patients (pts) with microsatellite instability-high/mismatch repair-deficient (MSI/dMMR) metastatic colorectal cancer (mCRC): Results of the GERCOR NIPICOL phase II study.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 101-101 ◽  
Author(s):  
Romain Cohen ◽  
Jaafar Bennouna ◽  
Julie Henriques ◽  
Christophe Tournigand ◽  
Christelle De La Fouchardiere ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Study ◽  
Checkpoint Inhibitors ◽  
Low Frequency ◽  
Progression Free Survival ◽  
Primary Objective ◽  
Free Survival ◽  
Previously Treated ◽  
Grade 3 ◽  
Clinical Trial Information

101 Background: Immune checkpoint inhibitors (ICKi) are highly effective for MSI/dMMR mCRC pts. RECIST1.1 criteria are reported to underestimate response to ICKi. The GERCOR NIPICOL phase II study aimed to evaluate disease control rate (DCR) using RECIST1.1 and iRECIST for MSI/dMMR mCRC pts treated with nivolumab (NIVO) and ipilimumab (IPI). Methods: MSI/dMMR mCRC pts previously treated with fluoropyrimidines (FP), oxaliplatin (OX) and irinotecan (IRI) ± targeted therapies received NIVO 3 mg/kg + IPI 1 mg/kg Q3W for 4 cycles then NIVO 3 mg/kg Q2W until progression or a maximum of 20 cycles. CT-scan tumor assessments were done every 6 weeks during 24 weeks and then every 12 weeks. Primary objective was DCR at 12 weeks (12wDCR) according to RECIST1.1 and iRECIST by central review. Response rates and progression-free survival (PFS) by central review were secondary objectives. A one-stage Fleming design was used with a targeted improvement of 12wDCR from 70% to 85%. Results: Of 57 pts included between Dec 2017 and Nov 2018, 43.9% had received ≥ 3 prior lines including FP (100%), OX (100%), IRI (95.5%), antiangiogenics (57.9%) and anti-EGFRs (45.6%). 17.5% of pts had BRAF mutation and 27.5% Lynch syndrome. Grade 3-4 treatment-related adverse events were reported in 49.1% of pts, mainly hepatitis (12.3%). 12wDCR was 86.0% and 87.7% using RECIST1.1 and iRECIST respectively, with only 1 pseudo-progression (1.8%) observed during the first 12 weeks, and one later. Kappa coefficient between RECIST and iRECIST 12wDCR was 0.92 (95%CI 0.77-1.0). Best observed responses with RECIST1.1/iRECIST were: 2/2 complete responses (3.5/3.5%), 19/19 partial responses (33.3/33.3%), 30/31 stable diseases (52.6/54.4%) and 3/2 disease progressions (5.3/3.5%), with 3 pts not evaluable (cancer-related deaths before first evaluation). Conclusions: Combination of NIVO and IPI in MSI/dMMR mCRC is associated with a low frequency of pseudo-progression and high DCR rate. PFS will be evaluated in Dec 2019, with all pts having completed the predefined 1-year of ICKi therapy. Clinical trial information: NCT033501260.

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