FORWARD I (GOG 3011): A randomized phase 3 study to evaluate the safety and efficacy of mirvetuximab soravtansine (IMGN853) versus chemotherapy in adults with folate receptor alpha (FRα)-positive, platinum-resistant epithelial ovarian cancer (EOC), primary peritoneal cancer, or primary fallopian tube cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. TPS5607-TPS5607 ◽  
Author(s):  
Kathleen N. Moore ◽  
Ignace Vergote ◽  
Ana Oaknin ◽  
Nicoletta Colombo ◽  
Susana N. Banerjee ◽  
...  
Keyword(s):  
Fallopian Tube ◽  
Folate Receptor ◽  
Single Agent ◽  
Objective Response ◽  
Pegylated Liposomal Doxorubicin ◽  
Phase 3 ◽  
Fallopian Tube Cancer ◽  
Primary Peritoneal Cancer ◽  
Peritoneal Cancer ◽  
Platinum Resistant

TPS5607 Background: Elevated FRα expression is characteristic of a number of solid tumors, including EOC, thereby providing an attractive candidate for targeted therapeutic approaches. Mirvetuximab soravtansine is an antibody-drug conjugate (ADC), comprising a FRα-binding antibody linked to the tubulin-disrupting maytansinoid DM4, that has shown single agent clinical activity and a favorable safety profile in an ongoing, first-in-human phase 1 trial (NCT01609556). Methods: FORWARD I is a randomized phase 3 study designed to evaluate the efficacy of mirvetuximab soravtansine compared with that of standard-of-care chemotherapy in adult patients with platinum-resistant EOC, primary peritoneal cancer, or fallopian tube cancer. Confirmation of FRα positivity by immunohistochemistry (medium or high expression; ≥ 50% of cells with at least moderate staining intensity) and ≤ 3 prior lines of therapy are required for inclusion. A maximum of 333 patients are expected to be recruited. Patients will be randomized 2:1 to Arm 1 (intravenous mirvetuximab soravtansine at a dose of 6.0 mg/kg, calculated using adjusted ideal body weight, on Day 1 of a 21-day cycle) or Arm 2 (investigators’ choice chemotherapy: paclitaxel, pegylated liposomal doxorubicin, or topotecan). The primary efficacy endpoint is progression-free survival (PFS; by blinded independent central review) and secondary endpoints include objective response rate, quality of life, overall survival, safety and tolerability, and duration of response. The first patient was enrolled in January 2017. Clinical trial information: NCT02631876.

Clinical Activity of Gemcitabine Plus Pertuzumab in Platinum-Resistant Ovarian Cancer, Fallopian Tube Cancer, or Primary Peritoneal Cancer

2010 ◽  
Vol 28 (7) ◽  
pp. 1215-1223 ◽  
Author(s):  
Sharmila Makhija ◽  
Lukas C. Amler ◽  
Dana Glenn ◽  
Frederick R. Ueland ◽  
Michael A. Gold ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Mrna Expression ◽  
Fallopian Tube ◽  
Single Agent ◽  
Objective Response ◽  
Clinical Activity ◽  
Fallopian Tube Cancer ◽  
Primary Peritoneal Cancer ◽  
Peritoneal Cancer ◽  
Platinum Resistant

Purpose Pertuzumab is a humanized monoclonal antibody that inhibits human epidermal growth factor receptor 2 (HER2) heterodimerization and has single-agent activity in recurrent epithelial ovarian cancer. The primary objective of this phase II study was to characterize the safety and estimate progression-free survival (PFS) of pertuzumab with gemcitabine in patients with platinum-resistant ovarian cancer. Patients and Methods Patients with advanced, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer who had received a maximum of one prior treatment for recurrent cancer were randomly assigned to gemcitabine plus either pertuzumab or placebo. Collection of archival tissue was mandatory to permit exploration of biomarkers that would predict benefit from pertuzumab in this setting. Results One hundred thirty patients (65 per arm) were treated. Baseline characteristics were similar between arms. The adjusted hazard ratio (HR) for PFS was 0.66 (95% CI, 0.43 to 1.03; P = .07) in favor of gemcitabine + pertuzumab. The objective response rate was 13.8% in patients who received gemcitabine + pertuzumab compared with 4.6% in patients who received gemcitabine + placebo. In patients whose tumors had low HER3 mRNA expression (< median, n = 61), an increased treatment benefit was observed in the gemcitabine + pertuzumab arm compared with the gemcitabine alone arm (PFS HR = 0.32; 95% CI, 0.17 to 0.59; P = .0002). Grade 3 to 4 neutropenia, diarrhea, and back pain were increased in patients treated with gemcitabine + pertuzumab. Symptomatic congestive heart failure was reported in one patient in the gemcitabine + pertuzumab arm. Conclusion Pertuzumab may add activity to gemcitabine for the treatment of platinum-resistant ovarian cancer. Low HER3 mRNA expression may predict pertuzumab clinical benefit and be a valuable prognostic marker.

Results from a phase II randomized, placebo-controlled, double-blind trial suggest improved PFS with the addition of pertuzumab to gemcitabine in patients with platinum-resistant ovarian, fallopian tube, or primary peritoneal cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 5507-5507 ◽  
Author(s):  
S. Makhija ◽  
D. Glenn ◽  
F. Ueland ◽  
M. Gold ◽  
D. Dizon ◽  
...  
Keyword(s):  
Fallopian Tube ◽  
Phase Ii ◽  
Survival Data ◽  
Single Agent ◽  
Erbb Receptors ◽  
Clinical Activity ◽  
Fallopian Tube Cancer ◽  
Primary Peritoneal Cancer ◽  
Peritoneal Cancer ◽  
Platinum Resistant

5507 Background: Pertuzumab (P) is a humanized monoclonal antibody that blocks the ability of HER2 to heterodimerize with other HER/ErbB receptors. As a single agent, P has demonstrated clinical activity in relapsed/refractory epithelial ovarian cancer (EOC). Since platinum-resistant (CDDP-R) EOC remains a difficult disease to treat, this phase II study was conducted to determine if addition of P to gemcitabine (G) would improve results. Methods: Patients with CDDP-R EOC (including ovarian, fallopian tube, or primary peritoneal cancer) who had received up to one prior treatment for CDDP-R disease were randomized to Gem 800 mg/m2 on D1, 8 of a 21-day cycle ± P or placebo (pl). P was given as an 840 mg initial dose followed by 420mg IV every 3 weeks. Tumor response was assessed by RECIST every 6 weeks using GOG criteria. The primary endpoint was progression free survival (PFS). Results: One hundred thirty patients (n = 65 each treatment cohort) were treated. Clinical characteristics were balanced between the treatment groups. Pts received a median of 2 prior regimens (range 1–6) for EOC. Based on 83 events, the adjusted hazard ratio for PFS was 0.67 (95% CI: 0.43–1.02), p =0.06 in favor of P+Gem. The median PFS was 3.0 months (0–8.7 months) vs. 2.6 months (0–9+ months), and the PFS rate at 4 months was 49% vs. 34% in the P+Gem and Gem/pl arms, respectively. The most common AEs increased in the P-treated pts were fatigue, nausea, diarrhea, back pain, Gr 3–4 neutropenia, rash, headache, stomatitis, epistaxis, and rhinorrhea. Clinically significant CHF was reported in one patient in the pertuzumab cohort. There was no imbalance in the LVEF results between treatment arms. One patient who received pertuzumab + gemcitabine experienced an adverse event that resulted in death (hemolytic-uremic syndrome). Conclusions: These data suggest that pertuzumab may add activity to gemcitabine as reflected by improvements in PFS in patients with CDDP-R ovarian, primary peritoneal, or fallopian tube cancer. Survival data will be presented at ASCO. No significant financial relationships to disclose.

MIRASOL (GOG 3045/ENGOT OV-55): A randomized, open-label, phase III study of mirvetuximab soravtansine versus investigator’s choice of chemotherapy in advanced high-grade epithelial ovarian, primary peritoneal, or fallopian tube cancers with high folate-alpha (FRα) expression.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. TPS6103-TPS6103
Author(s):  
Kathleen N. Moore ◽  
Toon Van Gorp ◽  
Jiuzhou Wang ◽  
Brooke Esteves ◽  
Patrick A Zweidler-McKay
Keyword(s):  
Fallopian Tube ◽  
Single Agent ◽  
Objective Response ◽  
Pegylated Liposomal Doxorubicin ◽  
Phase Iii ◽  
Clinical Activity ◽  
Antibody Drug Conjugate ◽  
Open Label ◽  
Fallopian Tube Cancer ◽  
Phase Iii Study

TPS6103 Background: Elevated FRα expression is a characteristic of several solid tumors, including epithelial ovarian cancer (EOC), thereby providing an attractive candidate for targeted therapeutic approaches. Mirvetuximab soravtansine is an antibody-drug conjugate (ADC) comprising a FRα-binding antibody, cleavable linker, and the maytansinoid DM4, a potent tubulin-targeting agent that has shown consistent and meaningful single agent clinical activity, along with favorable tolerability, in patients with high FRα expressing tumors. Methods: MIRASOL is a randomized phase III study designed to evaluate the efficacy of mirvetuximab soravtansine compared with that of standard-of-care chemotherapy in adult patients with platinum-resistant EOC, primary peritoneal cancer, or fallopian tube cancer. Confirmation of high FRα positivity by immunohistochemistry (high expression; ≥ 75% of cells with PS2+ staining intensity) and ≤ 3 prior lines of therapy are required for inclusion. MIRASOL is designed to randomize 430 patients, 1:1 to Arm 1 (intravenous mirvetuximab soravtansine at a dose of 6 mg/kg, calculated using adjusted ideal body weight, on Day 1 of a 21-day cycle) or Arm 2 (investigators’ choice chemotherapy: paclitaxel, pegylated liposomal doxorubicin, or topotecan). The primary efficacy endpoint is progression-free survival (PFS; by investigator) and secondary endpoints include objective response rate, quality of life, overall survival, and safety and tolerability. MIRASOL opened for enrollment in December 2019. Clinical trial information: NCT04209855.

scholarly journals Safety and Activity of Mirvetuximab Soravtansine (IMGN853), a Folate Receptor Alpha–Targeting Antibody–Drug Conjugate, in Platinum-Resistant Ovarian, Fallopian Tube, or Primary Peritoneal Cancer: A Phase I Expansion Study

2017 ◽  
Vol 35 (10) ◽  
pp. 1112-1118 ◽  
Author(s):  
Kathleen N. Moore ◽  
Lainie P. Martin ◽  
David M. O’Malley ◽  
Ursula A. Matulonis ◽  
Jason A. Konner ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Response Rate ◽  
Folate Receptor ◽  
Objective Response ◽  
Antibody Drug Conjugate ◽  
Primary Peritoneal Cancer ◽  
Peritoneal Cancer ◽  
Platinum Resistant ◽  
Duration Of Response ◽  
Antibody Drug

Purpose This phase I expansion cohort study evaluated the safety and clinical activity of mirvetuximab soravtansine (IMGN853), an antibody–drug conjugate consisting of a humanized anti–folate receptor alpha (FRα) monoclonal antibody linked to the tubulin-disrupting maytansinoid DM4, in a population of patients with FRα-positive and platinum-resistant ovarian cancer. Patients and Methods Patients with platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer received IMGN853 at 6.0 mg/kg (adjusted ideal body weight) once every 3 weeks. Eligibility included a minimum requirement of FRα positivity by immunohistochemistry (≥ 25% of tumor cells with at least 2+ staining intensity). Adverse events, tumor response (via Response Evaluation Criteria in Solid Tumors [RECIST] version 1.1), and progression-free survival (PFS) were determined. Results Forty-six patients were enrolled. Adverse events were generally mild (≤ grade 2), with diarrhea (44%), blurred vision (41%), nausea (37%), and fatigue (30%) being the most commonly observed treatment-related toxicities. Grade 3 fatigue and hypotension were reported in two patients each (4%). For all evaluable patients, the confirmed objective response rate was 26%, including one complete and 11 partial responses, and the median PFS was 4.8 months. The median duration of response was 19.1 weeks. Notably, in the subset of patients who had received three or fewer prior lines of therapy (n = 23), an objective response rate of 39%, PFS of 6.7 months, and duration of response of 19.6 weeks were observed. Conclusion IMGN853 exhibited a manageable safety profile and was active in platinum-resistant ovarian cancer, with the strongest signals of efficacy observed in less heavily pretreated individuals. On the basis of these findings, the dose, schedule, and target population were identified for a phase III trial of IMGN853 monotherapy in patients with platinum-resistant disease.

Efficacy and safety of tivozanib in recurrent, platinum-resistant ovarian, fallopian tube or primary peritoneal cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 5538-5538 ◽  
Author(s):  
Wendy M Swetzig ◽  
John Robert Lurain ◽  
Emily Berry ◽  
Mario Javier Pineda ◽  
Shohreh Shahabi ◽  
...  
Keyword(s):  
Fallopian Tube ◽  
Kinase Inhibitor ◽  
Progression Free Survival ◽  
Median Number ◽  
Vegf Receptor ◽  
Open Label ◽  
Fallopian Tube Cancer ◽  
Primary Peritoneal Cancer ◽  
Peritoneal Cancer ◽  
Platinum Resistant

5538 Background: Tivozanib is a potent, selective pan-vascular endothelial growth factor (VEGF) receptor tyrosine kinase inhibitor with a long half-life. This study assessed its activity in patients with recurrent, platinum-resistant ovarian cancer (OC), fallopian tube cancer (FTC) or primary peritoneal cancer (PPC). Methods: This open-label phase II study used a Simon’s two-stage design. Eligible patients had recurrent, platinum-resistant OC, FTC or PPC; ECOG PS of 0-1; normal end organ function; and measurable or detectable disease. There was no limit on the number of prior regimens. Treatment consisted of tivozanib 1.5 mg orally once daily (3 weeks on/1 week off). The primary endpoint was response rate. Secondary endpoints were progression-free survival (PFS), overall survival (OS), and toxicity assessment. If 1 partial response (PR) was observed in stage I [n = 12], enrollment proceeded to stage II. The null hypothesis was rejected for ≥ 4 responses in 30 patients. Results: Thirty-one patients were enrolled, and 30 were treated. Twenty-three had OC [76.67%], 5 FTC [16.67%] and 2 PPC [6.67%]. Twenty-six had measurable [86.67%] and 4 detectable disease [13.37%]. The median age was 60, and median number of prior regimens was 4 [range 1-9]. Four PRs [13.33%] were recorded. Twelve patients had stable disease (SD) [40%]. The clinical benefit rate (PR + SD) was 53%. Seven patients [23.33%] survived progression-free for > 6 mos. One patient continued treatment for > 2 yrs. The median PFS was 4 mos [range 1-25] and median OS was 8 mos [range 1-39]. There were no treatment-related deaths. Grade 3-4 related toxicities were hypertension [8], fatigue [3], fistula [2], hyponatremia [2], intestinal perforation, obstruction, stroke, proteinuria, hypomagnesemia, hypoalbuminemia, portal hypertension, nausea and anemia [1 each]. Frequent grade 1-2 related toxicities included fatigue [19], hypertension [13], anorexia [12], arthralgia [11], diarrhea [11], weight loss [10], hoarseness [8], headache [8] and nausea [7]. Exploratory analyses in tumor samples are ongoing. Conclusions: Tivozanib is active in patients with recurrent OC, FTC or PPC, without substantial toxicity, supporting its further development. Clinical trial information: NCT01853644.

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