scholarly journals Antitumor activity and safety of camrelizumab plus famitinib in patients with platinum-resistant recurrent ovarian cancer: results from an open-label, multicenter phase 2 basket study

2022 ◽  
Vol 10 (1) ◽  
pp. e003831
Author(s):  
Lingfang Xia ◽  
Jin Peng ◽  
Ge Lou ◽  
Mei Pan ◽  
Qi Zhou ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Antitumor Activity ◽  
Safety Profile ◽  
Objective Response ◽  
Recurrent Ovarian Cancer ◽  
Synergistic Activity ◽  
Phase 2 ◽  
Open Label ◽  
Multicenter Phase ◽  
Platinum Resistant

BackgroundCombination treatments with immune-checkpoint inhibitor and antiangiogenic therapy have the potential for synergistic activity through modulation of the microenvironment and represent a notable therapeutic strategy in recurrent ovarian cancer (ROC). We report the results of camrelizumab (an anti-programmed cell death protein-1 antibody) in combination with famitinib (a receptor tyrosine kinase inhibitor) for the treatment of platinum-resistant ROC from an open-label, multicenter, phase 2 basket trial.MethodsEligible patients with platinum-resistant ROC were enrolled to receive camrelizumab (200 mg every 3 weeks by intravenous infusion) and oral famitinib (20 mg once daily). All patients had disease progression during or <6 months after their most recent platinum-based chemotherapy. Primary endpoint was confirmed objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) V.1.1 based on investigator’s assessment. Secondary endpoints included disease control rate (DCR), duration of response (DoR), time to response (TTR), progression-free survival (PFS), overall survival (OS), 12-month OS rate and safety profile.ResultsOf the 37 women enrolled, 11 (29.7%) patients had primary platinum resistant, 15 (40.5%) patients had secondary platinum resistant and 11 (29.7%) patients had primary platinum refractory disease. As the cut-off date of April 9, 2021, nine (24.3%) patients had achieved a confirmed objective response, the ORR was 24.3% (95% CI, 11.8 to 41.2) and the DCR was 54.1% (95% CI, 36.9 to 70.5). Patients with this combination regimen showed a median TTR of 2.1 months (range, 1.8–4.1) and a median DoR of 4.1 months (95% CI, 1.9 to 6.3). Median PFS was 4.1 months (95% CI, 2.1 to 5.7), and median OS was 18.9 months (95% CI, 10.8 to not reached), with the median follow-up duration of 22.0 months (range, 12.0–23.7). The estimated 12-month OS rate was 67.2% (95% CI, 49.4 to 79.9). The most common ≥grade 3 treatment-related adverse events were hypertension (32.4%), decreased neutrophil count (29.7%) and decreased platelet count (13.5%). One (2.7%) patient died of grade 5 hemorrhage that was judged possibly related to study treatment by investigator.ConclusionThe camrelizumab with famitinib combination appeared to show antitumor activity in heavily pretreated patients with platinum-resistant ROC with an acceptable safety profile. This combination might provide a novel alternative treatment strategy in platinum-resistant ROC setting and warranted further exploration.Trial registration numberNCT03827837.

Anlotinib plus pemetrexed as a further treatment for patients with platinum-resistant ovarian cancer: A single-arm, open-label, phase II study.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 5533-5533
Author(s):  
Jueming Chen ◽  
Wei Wei ◽  
Lie Zheng ◽  
Han Li ◽  
Yanling Feng ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Adverse Events ◽  
Kinase Inhibitor ◽  
Antiangiogenic Therapy ◽  
Objective Response ◽  
Progression Free Survival ◽  
Recurrent Ovarian Cancer ◽  
Open Label ◽  
Platinum Resistant ◽  
Grade 3

5533 Background: Non-platinum chemotherapy is widely used in platinum-resistant recurrent ovarian cancer treatment but with limited efficacy. Combing chemotherapy with angiogenic inhibitors is a new therapeutic choice. Anlotinib is a novel tyrosine kinase inhibitor targeting multiple receptors involved in tumor proliferation, vasculature, and tumor microenvironment. The study aimed to further assess the efficacy and safety of anlotinib combined with pemetrexed in platinum-resistant ovarian cancer. Methods: Patients who had received at least two different chemotherapy regimens (including the first line platinum-based regimen), with histologically proven recurrent platinum-resistant or platinum-refractory epithelial ovarian cancer (including salpingocarcinoma and peritoneal carcinoma), ECOG 0-2, were considered eligible for enrollment to receive six 21-days cycles of anlotinib (12 mg QD from day 1 to 14; 21 days per cycle) orally plus pemetrexed intravenously (0.5 g/m2 on day 1; 21 days per cycle). Subsequent maintenance treatment was anlotinib monotherapy (12 mg QD from day 1 to 14; 21 days per cycle) till disease progression or intolerant toxicity. The primary endpoint was objective response rate (ORR), and the secondary endpoints included disease control rate (DCR), progression-free survival (PFS) and safety. Results: As of Jan 2021, 27 patients were enrolled. The median number of chemotherapy was 4 (range, 2-10) and 51.9% (14/27) of patients had ever received antiangiogenic therapy. The ORR was 36.4% (partial response (PR) in 8 patients; 95% CI, 17.2-59.3). The DCR was 100.0% (PR in 8 patients and stable disease (SD) in 14 patients; 95% CI, 73.5-100). The median time of the first response was 1.6 months (range, 1.3-4.4). The median PFS was 9.3 months (95% CI, NE-NE). Furthermore, the ORR of patients with and without prior antiangiogenic therapy was 16.7% (95%CI, 2.1-48.4) and 60.0% (95%CI, 26.2-87.8) respectively (P = 0.074). Any grades of adverse events (AEs) were observed in 92.6% (25/27) of patients, containing allergic eruption (33.3%), hand-foot syndrome (29.6%), hypertension (25.9%), and fatigue (25.9%). The grade 3-4 adverse events were only observed in 5 patients, including 1 with grade 3 proteinuria, 1 with grade 3 ascites, 1 with grade 3 fatigue, 1 with grade 3 edema limbs and 1 with grade 4 anemia. Conclusions: The treatment of anlotinib plus pemetrexed showed a promising antitumor activity with tolerable toxicity for patients in platinum-resistant and refractory ovarian cancer. Clinical trial information: ChiCTR2000029654.

Trastuzumab deruxtecan (T-DXd; DS-8201) in patients (pts) with HER2-expressing metastatic colorectal cancer (mCRC): Final results from a phase 2, multicenter, open-label study (DESTINY-CRC01).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 3505-3505
Author(s):  
Takayuki Yoshino ◽  
Maria Di Bartolomeo ◽  
Kanwal Pratap Singh Raghav ◽  
Toshiki Masuishi ◽  
Fotios Loupakis ◽  
...  
Keyword(s):  
Safety Profile ◽  
Topoisomerase I ◽  
Objective Response ◽  
Safety Data ◽  
Progression Free Survival ◽  
Drug Discontinuation ◽  
Phase 2 ◽  
Antibody Drug Conjugate ◽  
Primary Analysis ◽  
Open Label

3505 Background: T-DXd is an antibody–drug conjugate of a humanized anti-HER2 antibody bound to a topoisomerase I inhibitor by a cleavable linker. The primary analysis of DESTINY-CRC01 (DS8201-A-J203; NCT03384940), a phase 2, open-label, multicenter study of T-DXd in pts with HER2-expressing mCRC showed promising antitumor activity and a manageable safety profile (cohort A median follow-up [FU], 27.1 weeks; Siena S, ASCO 2020). We present updated longer-term efficacy and safety data. Methods: Pts had centrally confirmed HER2-expressing, RAS wild-type mCRC that progressed after ≥2 prior regimens. 6.4 mg/kg of T-DXd was administered every 3 weeks (Q3W) in 3 cohorts (A: HER2 IHC3+ or IHC2+/ISH+; B: IHC2+/ISH−; C: IHC1+). The primary end point was confirmed objective response rate (ORR) by independent central review in cohort A. Secondary end points were disease control rate (DCR; CR + PR + SD), duration of response (DOR), progression-free survival (PFS), and overall survival (OS). Results: At data cutoff (Dec 28, 2020), 86 pts (A, 53; B, 15; C, 18) received T-DXd. Median age was 58.5 y (range, 27-79), 53.5% were male, and 90.7% had left colon or rectum cancer. Median prior regimens for metastatic disease was 4 (range, 2-11). All pts had prior irinotecan; 30.2% in cohort A had prior anti-HER2 therapy. Median (m) treatment duration (all pts) was 3.0 mo (95% CI, 2.1-4.1; cohort A, 5.1 mo [95% CI, 3.9-7.6]). In cohort A (median FU, 62.4 weeks), confirmed ORR was 45.3% (24/53 pts; 95% CI, 31.6-59.6), DCR was 83.0% (44/53 pts; 95% CI, 70.2-91.9), mDOR was 7.0 mo (95% CI, 5.8-9.5), mPFS was 6.9 mo (95% CI, 4.1-8.7) with 37 (69.8%) PFS events, and mOS was 15.5 mo (95% CI, 8.8-20.8) with 36 (67.9%) OS events. These results are consistent with the primary analysis. Confirmed ORR was 43.8% (7/16 pts; 95% CI, 19.8-70.1) in pts with prior anti-HER2 therapy, 57.5% (23/40 pts; 95% CI, 40.9-73.0) in pts with IHC3+ status, and 7.7% (1/13 pts; 95% CI, 0.2-36.0) in pts with IHC2+/ISH+ status. In cohorts B and C, mPFS was 2.1 mo (95% CI, 1.4-4.1) and 1.4 mo (95% CI, 1.3-2.1); mOS was 7.3 mo (95% CI, 3.0-NE) and 7.7 mo (95% CI, 2.2-13.9), respectively. Treatment-emergent adverse events (TEAEs) of grade (G) ≥3 occurred in 65.1% of pts (56/86); the most common TEAEs were hematologic and gastrointestinal. TEAEs leading to drug discontinuation occurred in 13 pts (15.1%). 8 pts (9.3%) had interstitial lung disease (ILD) adjudicated by an independent committee as related to T-DXd (4 G2; 1 G3; 3 G5). Conclusions: T-DXd at 6.4 mg/kg Q3W showed promising activity and durability with longer-term FU in this pt population. The safety profile was consistent with prior results; ILD continues to be recognized as an important identified risk that requires careful monitoring and intervention as needed. These results support continued exploration of T-DXd in pts with HER2-overexpressing mCRC. Clinical trial information: NCT03384940.

Antitumor activity and safety of pembrolizumab in patients with advanced recurrent ovarian cancer: Interim results from the phase 2 KEYNOTE-100 study.

2018 ◽  
Vol 36 (15_suppl) ◽  
pp. 5511-5511 ◽  
Author(s):  
Ursula A. Matulonis ◽  
Ronnie Shapira-Frommer ◽  
Alessandro Santin ◽  
Alla Sergeevua Lisyanskaya ◽  
Sandro Pignata ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Antitumor Activity ◽  
Recurrent Ovarian Cancer ◽  
Phase 2

Weekly association of gemcitabine and topotecan in early recurrent ovarian cancer patients: A French multicenter phase II study

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 16016-16016
Author(s):  
F. Joly ◽  
T. Petit ◽  
P. Pautier ◽  
E. Guardiola ◽  
F. Mayer ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Survival Time ◽  
Phase Ii ◽  
Stable Disease ◽  
Response Rate ◽  
Phase Ii Study ◽  
Objective Response ◽  
Recurrent Ovarian Cancer ◽  
First Line ◽  
Multicenter Phase

16016 Background: A weekly association of gemcitabine and topotecan was tested with the aim of evaluating its efficacy and tolerance in patients recurring after first line platinum and taxane-based chemotherapy. Methods: From December 2004 to April 2006, 77 patients whose disease has progressed within 12 months (time-free interval, TFI) after first line chemotherapy were enrolled in a multicenter phase II study. Primary endpoint was overall response rate (ORR). Gemcitabine (1000 mg/m2) and topotecan (2.5 mg/m2) were given day 1, 8 and 15 (q 28 d) for 6 to 9 cycles. Tumor response was assessed according to RECIST or Rustin criteria. Clinical response was assessed using symptoms improvement in responders and patients with stable disease. Follow-up was updated December 2006. Results: Initial characteristics were: median age 63 years (38 to 80), WHO PS 0–1 93%, serous histology 85%, TFI < 6 months 45%, measurable disease 71%. Four cycles (1 to 8) were administered in average. The only major toxicity was neutropenia (Grade 3 and 4 in 17% and 6% of patients) with one febrile neutropenia; one toxic death (pneumopathy) was observed. 34% of cycles were incomplete (d8 and/or d15 not administered) because of grade 1–2 thrombopenia or grade 1–4 neutropenia. Lenograstim and erythropoietin were administered in 14% and 34% of patients, respectively. Sixty-six (86%) patients were evaluable for response (2 cycles administered). The ORR was 14% (CR=3%, PR=11%); there were 53% of stable disease. ORR was 7% and 20% in patients with TFI < 6 months and = 6 months, respectively. Symptoms were improved in 18 (64%) of 28 patients and pain in 11 (39%) of 28 patients. Median event-free survival time was 3.7 months. Median overall survival time was 12.3 months (7.5 and 15.6 months in patients with TFI < 6 months and = 6 months, respectively; p=0.0244). Conclusions: In resistant/refractory ovarian cancer, weekly gemcitabine and topotecan is associated with low objective response rate but with a high proportion of stable disease and symptoms control leading to acceptable quality of life. No significant financial relationships to disclose.

A randomized phase 2 trial comparing efficacy of the combination of the PARP inhibitor olaparib and the antiangiogenic cediranib against olaparib alone in recurrent platinum-sensitive ovarian cancer.

2014 ◽  
Vol 32 (18_suppl) ◽  
pp. LBA5500-LBA5500 ◽  
Author(s):  
Joyce Liu ◽  
William Thomas Barry ◽  
Michael J. Birrer ◽  
Jung-min Lee ◽  
Ronald J. Buckanovich ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Phase 1 ◽  
Parp Inhibitor ◽  
Objective Response ◽  
Progression Free Survival ◽  
Recurrent Ovarian Cancer ◽  
Parp Inhibitors ◽  
Open Label ◽  
Angiogenic Therapy ◽  
Platinum Sensitive

LBA5500 Background: PARP inhibitors and anti-angiogenics are clinically active in recurrent ovarian cancer (OvCa). Preclinical studies suggest these agents can synergize, and a phase 1 study showed that the combination of cediranib (ced) and olaparib (olap) is well-tolerated. We therefore compared the activity of olap alone (Olap) to combined ced and olap (Ced/Olap) in treatment of recurrent platinum-sensitive (plat-sens) high-grade serous (HGS) or BRCA-related OvCa (NCT 01116648). Methods: Patients (pts) across 9 centers were randomized 1:1 in this Ph 2 open label study to Olap (olap 400 mg capsules BID) or Ced/Olap (olap 200 mg capsules BID; ced 30 mg daily), stratified by BRCA status and prior anti-angiogenic therapy. Eligibility included pts with recurrent plat-sens HGS or BRCA-related OvCa. Pts had measurable disease by RECIST 1.1, PS 0 or 1, and the ability to take POs. No prior anti-angiogenics in the recurrent setting or prior PARP inhibitor was allowed. Progression-free survival (PFS) was defined as time from randomization to radiographic progression or death. With a target N=90 pts, the study was powered to detect a hazard ratio (HR) of 1.75 (median PFS 6 vs 10.5 mo). Results: Pts were enrolled from Oct 2011 to Jun 2013: 46 to Olap, 44 to Ced/Olap. 48 pts were known BRCA carriers (25 Olap; 23 Ced/Olap). At a planned interim analysis the DSMB recommended release of data. As of Jan 7, 2014, 41 pts had a PFS event. Median PFS was 9.0 mos for Olap and 17.7 mos for Ced/Olap (HR 2.9, 95% CI 1.5-5.6, p = 0.001). There were 2 complete responses (CR) and 21 partial responses (PR) in pts on Olap (56% objective response rate, ORR) and 3 CRs and 33 PRs in pts on Ced/Olap (84% ORR, p = 0.008). The overall rate of Gr3/4 toxicity was higher for pts on Ced/Olap (70%) than on Olap (7%). Differentially occurring toxicities included fatigue (27% Ced/Olap vs 7% Olap), diarrhea (23% vs 0%), and hypertension (39% vs 0%). Updated efficacy and exploratory subgroup analyses will be presented. Conclusions: Combined Ced/Olap significantly extended PFS and ORR compared to Olap in plat-sens OvCa. Further studies of this oral combination in plat-sens OvCa are warranted. Clinical trial information: NCT01116648.

FIDES-02, a phase Ib/II study of derazantinib (DZB) as monotherapy and combination therapy with atezolizumab (A) in patients with surgically unresectable or metastaticurothelial cancer (UC) and FGFR genetic aberrations.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. TPS590-TPS590
Author(s):  
Arvind Chaudhry ◽  
Cora N. Sternberg ◽  
Maria De Santis ◽  
Joaquim Bellmunt ◽  
Andrea Necchi ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Kinase Inhibitor ◽  
Objective Response ◽  
Treatment Phase ◽  
Maximal Effect ◽  
Phase 2 ◽  
Open Label ◽  
Genetic Aberrations ◽  
Combination Methods ◽  
Phase 1B

TPS590 Background: Deregulation of the FGFR signaling pathway is implicated in various cancers. In UC, FGFR genetic aberrations include FGFR1/2/3 mutations (M) and, less commonly, fusions (F), while the role of amplifications warrants further research. Prognosis of UC patients is overall poor and treatment options are limited. DZB is an oral small-molecule FGFR1/2/3 and CSF1R kinase inhibitor, which demonstrated promising antitumor activity in preclinical studies, including FGFR-driven patient-derived xenograft models. Preclinical data show that DZB reduced CSF1-stimulated CSF1R phosphorylation in macrophages, with a maximal effect similar to the CSF1R inhibitor BLZ945, suggesting DZB could have an effect on tumor-associated macrophage regulation. Thus, DZB+A (PD-L1 immune-checkpoint blockade [ICB]) is a rationale combination for immunogenic tumors like UC. FIDES-02 is a multicenter, multicohort open-label Phase 1b/2 study evaluating the effect of DZB as monotherapy and DZB+A combination. Methods: The study evaluates 300 mg DZB p.o. daily or DZB+A (1200 mg i.v.) in UC patients with FGFR1-3 M/F per liquid or tissue biopsy-based NGS. Cohort 1 (C1) enrolls pts after one or more standard chemotherapy ± ICB regimens (Phase 2; treatment: DZB); C2 enrolls patients with any advanced solid tumor, any FGFR status, any prior treatment (Phase 1b; for RP2D of DZB+A); C3 enrolls first-line patients with cisplatin-ineligible, PD-L1-low UC (Phase 2; DZB v DZB+A); C4 enrolls UC patients resistant to FGFR inhibitor treatment (Phase 2; DZB v DZB+A). Treatment will continue until disease progression, intolerance, withdrawal of informed consent, or death. Using Simon’s two-stage designs, objective response rate (per RECIST 1.1 central review) is the primary endpoint to assess the antitumor activity of DZB or DZB+A in Ph2. Main secondary objectives include evaluation of median PFS, duration of response, safety profile, HR-QoL (incl., QLQ C30, FACT-Bl, EQ-5D), and symptom response from baseline. The study was initiated in July 2019 and C1 (N=71) and C2 (N=24) are currently open for enrollment. Clinical trial information: NCT04045613.

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