Found 3 Presentations For Request "mirvetuximab"

Poster Display session 2 Poster Display session

1028P - Mirvetuximab soravtansine, a folate receptor alpha (FRa)-targeting antibody-drug conjugate (ADC), in combination with carboplatin and bevacizumab: Initial results from a phase Ib study in patients (pts) with ovarian cancer (ID 4410)

Presentation Number
1028P
Lecture Time
12:00 - 12:00
Speakers
  • David Omalley (Columbus, United States of America)
Session Name
Poster Display session 2
Location
Poster Area (Hall 4), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
12:00 - 13:00

Abstract

Background

Mirvetuximab soravtansine (MIRV) is an ADC comprising a FRα-binding antibody, cleavable linker, and the maytansinoid DM4, a potent tubulin-targeting agent. MIRV is being evaluated in combination with carboplatin and bevacizumab (BEV) as part of the ongoing phase 1b study FORWARD II.

Methods

Eligible pts had platinum-sensitive, recurrent epithelial ovarian, primary peritoneal, or fallopian tube cancer (platinum-free interval >6 months), 1 or 2 prior lines of therapy, and FRα positivity by immunohistochemistry (≥ 50% of tumor cells with at least moderate staining intensity). MIRV was administered at 6 mg/kg (adjusted ideal body weight) in combination with carboplatin (AUC 5) and BEV (15 mg/kg) on Day 1 of a 21-day cycle. MIRV and BEV were continued as maintenance after completing carboplatin. Responses were assessed with RECIST 1.1 and adverse events (AEs) by CTCAE v4.03.

Results

Forty-one pts received full dosing of the triplet combination, with a median of 9 cycles each of MIRV (range, 3-16) and BEV (1-18) and 6 cycles of carboplatin (3-8) at the time of interim analysis; 31 pts remain on study. Low grade diarrhea (all grades, 76%; [grade 3, 7%]), nausea (68%; [2%]), and fatigue (59%; [5%]), the most common treatment-emergent AEs, were consistent with the safety profile of MIRV as monotherapy, albeit more frequent. AEs typically associated with carboplatin (thrombocytopenia [39% ≥ grade 3] and neutropenia [20% ≥ grade 3]) and BEV (hypertension [27% grades 1-3]) were also observed. To date, no deaths have occurred. The confirmed objective response rate was 80%, including 7 complete responses and 26 partial responses. With a median follow-up time of 6.8 months, progression-free survival data are immature.

Conclusions

Full dose MIRV was readily combined with standard dosing for both BEV and carboplatin, with a manageable AE profile as anticipated for a combination of these three agents. No new safety signals have been identified. The preliminary signals of clinical activity are encouraging and justify further exploration of this novel therapeutic combination.

Clinical trial identification

NCT02606305.

Legal entity responsible for the study

ImmunoGen, Inc.

Funding

ImmunoGen, Inc.

Disclosure

D. O\'Malley: Advisory / Consultancy: Agenus; Advisory / Consultancy: Roche/Genentech; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: ImmunoGen; Advisory / Consultancy: OncoQuest; Advisory / Consultancy: Tesaro; Advisory / Consultancy: Ambry; Advisory / Consultancy: Clovis; Advisory / Consultancy: Janssen; Advisory / Consultancy: AbbVie; Advisory / Consultancy: Novocure; Advisory / Consultancy: Regeneron; Advisory / Consultancy: Myriad. L. Gilbert: Honoraria (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: AstraZeneca; Honoraria (self): Roche; Honoraria (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: Pfizer; Research grant / Funding (institution): Astex Pharmaceuticals; Research grant / Funding (institution): Tesaro; Research grant / Funding (institution): ImmunoGen. C. Castro: Advisory / Consultancy: N-of-One; Advisory / Consultancy: Advanced Medical; Advisory / Consultancy: InfiniteMD; Research grant / Funding (institution): ImmunoGen; Licensing / Royalties: Exosome Diagnostics. U.A. Matulonis: Advisory / Consultancy: ImmunoGen Inc; Advisory / Consultancy: Fujifilm; Advisory / Consultancy: Geneos; Advisory / Consultancy: 2X Oncology; Advisory / Consultancy: Mersana; Advisory / Consultancy: Merck. K. Malek: Full / Part-time employment: ImmunoGen Inc. K.N. Moore: Honoraria (self), Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: ImmunoGen; Advisory / Consultancy: Tesaro; Advisory / Consultancy: Genentech/Roche; Advisory / Consultancy: Clovis; Advisory / Consultancy: VBL Therapeutics; Advisory / Consultancy: Aravive; Advisory / Consultancy: Merck; Advisory / Consultancy: Janssen; Advisory / Consultancy: OncoMed. All other authors have declared no conflicts of interest.

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Proffered Paper 2 – Gynaecological cancers Proffered Paper session

992O - FORWARD I (GOG 3011): A phase III study of mirvetuximab soravtansine, a folate receptor alpha (FRa)-targeting antibody-drug conjugate (ADC), versus chemotherapy in patients (pts) with platinum-resistant ovarian cancer (PROC) (ID 4093)

Presentation Number
992O
Lecture Time
08:30 - 08:45
Speakers
  • Kathleen N. Moore (Oklahoma City, Oklahoma, United States of America)
Location
Madrid Auditorium (Hall 2), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
08:30 - 10:00

Abstract

Background

Mirvetuximab soravtansine (MIRV) is an ADC comprising a FRα-binding antibody, cleavable linker, and the maytansinoid DM4, a potent tubulin-targeting agent. FORWARD I, a phase III study, evaluated the safety and efficacy of MIRV compared to chemotherapy in pts with PROC.

Methods

Pts with PROC, 1-3 prior lines of therapy, and FRα positivity by immunohistochemistry (stratified by predefined medium or high expression) were enrolled. Pts were randomized 2:1 to MIRV (6 mg/kg, adjusted ideal body weight) once every 21 days or investigators’ choice chemotherapy (paclitaxel, pegylated liposomal doxorubicin, or topotecan). The primary endpoint was progression-free survival (PFS) by blinded independent review committee, in both the intention-to-treat (ITT) population (medium and high FRα expression) and, separately, in pts with high FRα. Secondary endpoints included objective response rate (ORR) and overall survival (OS). Median follow-up time was 12.5 months.

Results

Of 366 pts randomized, 248 received MIRV and 118 chemotherapy. Baseline characteristics were well balanced across arms. In the ITT population, the PFS hazard ratio (HR) was 0.981 (median PFS of 4.1 vs 4.4 months for MIRV and chemotherapy, respectively). For the high FRα pt subset (n = 218), additional outcomes favored MIRV over chemotherapy: PFS HR of 0.693 (4.8 vs 3.3 months; p = 0.049, not significant by Hochberg procedure), ORR (24% vs 10%), and interim OS (83/213 events (34%); median not reached vs 11.8 months; HR, 0.618). The most common adverse events (AEs) observed with MIRV were nausea (54%), diarrhea (44%), and blurred vision (43%). Fewer high grade (≥ 3) events, dose modifications, and discontinuations due to AEs were seen with MIRV.

Conclusions

While the study did not meet the primary endpoint, promising and consistent efficacy measures were observed in the predefined subset of high FRα PROC pts treated with MIRV. Along with favorable tolerability and differentiated safety, these findings suggest a favorable benefit-risk profile for MIRV in this biomarker-defined and difficult-to-treat population.

Clinical trial identification

NCT02631876.

Legal entity responsible for the study

ImmunoGen, Inc.

Funding

ImmunoGen, Inc.

Disclosure

K.N. Moore: Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Clovis; Advisory / Consultancy: ImmunoGen; Advisory / Consultancy: Genentech/Roche; Advisory / Consultancy: Tesaro; Advisory / Consultancy: VBL Therapeutics; Advisory / Consultancy: Aravive. A. Oaknin: Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Advisory / Consultancy, Travel / Accommodation / Expenses: AstraZeneca; Advisory / Consultancy, Travel / Accommodation / Expenses: PharmaMar; Advisory / Consultancy, Travel / Accommodation / Expenses: Clovis; Advisory / Consultancy, Travel / Accommodation / Expenses: Tesaro; Advisory / Consultancy: ImmunoGen. D. Lorusso: Advisory / Consultancy, Research grant / Funding (institution): Tesaro; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy, Research grant / Funding (institution): Merck; Advisory / Consultancy, Research grant / Funding (institution): Clovis; Advisory / Consultancy: Merrimack. C.G. Murphy: Advisory / Consultancy: Janssen; Advisory / Consultancy: Roche; Advisory / Consultancy: Nordic Pharma; Travel / Accommodation / Expenses: Ipsen; Travel / Accommodation / Expenses: Pfizer. J.A. Konner: Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Clovis; Advisory / Consultancy: ImmunoGen. M. Prasad Hayes: Research grant / Funding (institution): AstraZeneca. S.K. Kim: Advisory / Consultancy, Research grant / Funding (self), Travel / Accommodation / Expenses: AbbVie; Advisory / Consultancy: Cytomx; Advisory / Consultancy: ImmunoGen; Advisory / Consultancy: Seattle Genetics; Advisory / Consultancy, Travel / Accommodation / Expenses: Astellas/Agensys. J. Wang: Full / Part-time employment: ImmunoGen Inc. P. Pautier: Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Advisory / Consultancy, Travel / Accommodation / Expenses: AstraZeneca; Travel / Accommodation / Expenses: Clovis; Advisory / Consultancy, Travel / Accommodation / Expenses: Tesaro. M.J. Birrer: Advisory / Consultancy: Tesaro; Advisory / Consultancy: Clovis; Advisory / Consultancy: Merck Sharp & Dome; Advisory / Consultancy: Genentech USA; Advisory / Consultancy: AstraZeneca. All other authors have declared no conflicts of interest.

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Poster Display session 1 Poster Display session

58P - IKS01, a next generation antibody drug conjugate (ADC) designed to be efficacious in tumors with low and moderate levels of folate receptor expression (ID 2497)

Presentation Number
58P
Lecture Time
12:00 - 12:00
Speakers
  • Jenny Thirlway (Newcastle-upon-Tyne, United Kingdom)
Session Name
Poster Display session 1
Location
Poster Area (Hall 4), Fira Gran Via, Barcelona, Spain
Date
28.09.2019
Time
12:00 - 13:00

Abstract

Background

Frequent over-expression of FRA in ovarian and non-small-cell lung cancer (NSCLC), and relative lack of expression in normal tissue, make it an attractive therapeutic target. Ovarian cancer is the ninth most common cancer in women and the leading cause of death in gynaecological cancer. Lung cancer remains a leading cause of cancer-related death with NSCLC accounting for 80 % of cases. ADCs are the focus of intense interest as a means to provide selective tumor killing with increased efficacy and less off-target toxicity than standard of care chemotherapies. Clinical evaluation of mirvetuximab soravtansine in solid tumor indications demonstrated that FRA can be successfully targeted by an ADC. However, anti-tumor activity appears to be generally limited to patients whose tumors express high levels of FRA. IKS01 is an ADC comprised of an FRA-targeting antibody conjugated via Iksuda’s PermaLink conjugation technology to Femtogenix’s highly potent FGX2-62 payload. FGX2-62 is a pyrridinobenzodiazepine DNA mono-alkylating agent with pM potency in a range of tumor cell lines. IKS01 has been designed to be sufficiently potent to have target-dependent efficacy even in tumors with low or moderate expression of the target antigen.

Methods

IKS01 was generated with a drug to antibody ratio of 2. Efficacy was evaluated in human cell line derived xenograft models with a range of FRA expression, including the choriocarcinoma Jeg-3 model (high expression), the ovarian adenocarcinoma OV-90 model (low expression) and the lung adenocarcinoma NCI-H2110 model (moderate expression). An FRA-targeting benchmark ADC with a format that has shown clinical efficacy was included for comparison.

Results

IKS01 is highly effective in causing tumor regressions in FRA-expressing tumor models at doses that are well tolerated. IKS01 was significantly more active than benchmark ADC in the high FRA-expressing Jeg-3 model and caused complete or near complete regressions in low/moderate FRA-expressing xenograft models where the benchmark ADC showed limited or no activity.

Conclusions

IKS01 shows marked anti-tumor efficacy in pre-clinical models of ovarian and lung cancer, even in models with low or moderate FRA expression.

Legal entity responsible for the study

Iksuda Therapeutics Ltd.

Funding

Iksuda Therapeutics Ltd.

Disclosure

J. Thirlway: Shareholder/Stockholder/Stock options: Iksuda Therapeutics Ltd. A. Lodge: Shareholder/Stockholder/Stock options: Iksuda Therapeutics Ltd. A. Pelava: Shareholder/Stockholder/Stock options: Iksuda Therapeutics Ltd. D.J. Williamson: Shareholder/Stockholder/Stock options: Iksuda Therapeutics Ltd. D. Carta: Shareholder/Stockholder/Stock options: Iksuda Therapeutics Ltd. M. Al Nakeeb: Shareholder/Stockholder/Stock options: Iksuda Therapeutics Ltd. J. Mysliwy: Shareholder/Stockholder/Stock options: Iksuda Therapeutics Ltd. P.J.M. Jackson: Shareholder/Stockholder/Stock options: Femtogenix Ltd. D.E. Thurston: Shareholder/Stockholder/Stock options: Femtogenix Ltd. R.J. Lutz: Shareholder/Stockholder/Stock options: Iksuda Therapeutics Ltd.

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