David Fernandez Ferrer

On ImmunoGen and Mirvetuximab Soravtansine (IMGN 853), a Subjective Meta-Analysis from

a Clinical Trial Based Perspective

March 1, 2019
 Pre-Analysis Data

Immunogen currently has two ongoing phase 3 clinical trials relating to ovarian cancer; both
estimated to be completed within the next 4 months. Right now, the nearest one to completion is
February of this month, should be completed within the next few weeks.
https://clinicaltrials.gov/ct2/show/NCT02631876?cond=MIRVETUXIMAB+SORAVTANSINE
&rank=5
This is a Phase 3, open label, randomized study designed to compare the safety and efficacy of
IMGN853 to that of selected single-agent chemotherapy (Investigator's choice) in women with
platinum-resistant FR-alpha positive advanced EOC, primary peritoneal cancer and/or fallopian
tube cancer.
N = 333
Randomized, open label phase 3 to study and evaluate the safety and efficacy of Mirvetuximab
Soravtansine (IMGN853) Versus Investigator's Choice of Chemotherapy in Women with Folate
Receptor Alpha Positive Advanced Epithelial Ovarian Cancer, Primary Peritoneal Cancer or
Fallopian Tube Cancer.

Mirvetuximab
Soravtansine,
chemical
structure

Study completion date: February 2019

Method of administration study:
Arm 1: IMGN853 administered at 6mg/kg AIBW () once every three weeks (Q3W)
Arm 2: Paclitaxel, Pegylated Liposomal Doxorubicin, or Topotecan
Primary Outcome: Progression free survival in all patients randomized to the study and in
patients with high folate receptor alpha expression [ Time Frame: Up to 2 years]
Study Director: Karim Malek, MD ImmunoGen, Inc
Clinical Trial ID: NCT02631876
Mechanism of Action (MOA): ADC, this drug is a potential new treatment for patients with
folate receptor alpha (Fra)-positive cancer. Includes ovarian cancers primarily; as well as other
solid tumors.
Fra is a protein that is encoded by the FOLR1 gene. Has a high affinity for folic acid and for
several reduced folic acid derivatives and mediate delivery of 5 methyltetrahydrofolate to the
interior of cells.
Fra can be overexpressed by a number of epithelial derived tumors including ovarian breast renal
lung and colorectal and brain.
COMPETITOR??? – Farletuzumab for ovarian cancer. Farletuzumab was developed by
Morphotek. It targeted FR-Alpha (FRa) in order to cure ovarian cancer.
Drugs that are already used to treat ovarian cancer include Carboplatin and Taxane.
Farletuzumab phase 3 study performed over a period of 6 years from 2009 to 2015 tested
n=1100; included patients whom: A histologically or cytologically confirmed diagnosis of non-
mucinous epithelial ovarian cancer including primary peritoneal or fallopian tube malignancies
Subjects who have received other therapy to treat their ovarian cancer since relapse
Study was fairly diversified as it included many third world countries as well as first world
countries in it. Study performed by company known as MORPHOTEK.

Farletuzumab (MORAb-003) is a fully humanized monoclonal antibody against the folate

receptor alpha, for the potential treatment of epithelial ovarian cancer.

Number to call Morphotek; http://www.morphotek.com/ 610-423-6100

The candidate is also being assessed in combination regimens for both platinum-resistant and
platinum-sensitive disease in the Phase 1b/2 FORWARD II trial.
https://www.immunogen.com/wp-content/uploads/2018/10/ESMO-2018-PEMBRO-Poster-
FINAL-compressed.pdf

Conclusions from most recent study for IMGN853:

The combination of mirvetuximab soravtansine and pembrolizumab continues to demonstrate
favorable tolerability in patients with PROC, with predominantly mild-to moderate (≤ Grade 2)
events • The safety profile is consistent with the known adverse drug reactions of each agent,
with pneumonitis representing a potential overlapping toxicity • The initial antitumor activity of
mirvetuximab soravtansine combined with pembrolizumab is consistent with mirvetuximab
soravtansine monotherapy in heavily pretreated patients and encouraging when considering
outcomes reported for pembrolizumab-based combinations evaluated to date in PROC • 83% of
patients had tumor shrinkage with combination treatment, with more robust reductions seen in
medium/high FRα tumors • 30% confirmed ORR in heavily pretreated PROC (37% with 4+ prior
lines) compares favorably to that observed for other pembrolizumab combinations in less heavily
pretreated populations5,6 • Early DOR data (median 6.9 months) suggest a trend towards
improvement over mirvetuximab soravtansine monotherapy • With 16 patients still on study (all
with medium/high FRα expression) and a median follow up time of 8.3 months, the efficacy data
are immature. Final data will be presented with longer-term follow up
https://www.immunogen.com/wp-content/uploads/2018/10/ESMO-2018-PEMBRO-Poster-
FINAL-compressed.pdf

One approach is based on conjugates of folate analogs, such as vintafolide, where payloads are
delivered by targeting the high affinity folate binding site of the receptor. A second approach is
to use antibodies or antibody-like binders that target the FRα protein. Both naked antibodies
(farletuzumab) and antibody conjugates (IMGN853) are being evaluated.
These drugs also treat for Ovarian Epithelial Cancer:
Letrozole: non-steroidal aromatase inhibitor. Letrozole is approved by the United States Food
and Drug Administration (FDA) for the treatment of local or metastatic breast cancer that is
hormone receptor positive or has an unknown receptor status in postmenopausal women. There
is concern that long term use may lead to osteoporosis, which is why prescriptions of Letrozole
are often accompanied by prescriptions of osteoporosis-fighting medication such as
Fosamax. Above 5mg/day for extended periods may cause kidney problems.
Melphalan: An alkylating nitrogen mustard that is used as an antineoplastic in the form of the
levo isomer - melphalan, the racemic mixture - merphalan, and the dextro isomer - medphalan;
toxic to bone marrow, but little vesicant action; potential carcinogen.
Niraparib: Niraparib is an orally active PARP inhibitor developed by Tesaro to treat ovarian
cancer. FDA approval on March 2017.
Olaparib: Olaparib is an inhibitor of poly (ADP-ribose) polymerase (PARP) enzymes; Olaparib
has been shown to inhibit growth of select tumor cell lines in vitro and decrease tumor growth in
mouse xenograft models of human cancer both as monotherapy or following platinum-based
chemotherapy. In a randomized clinical trial involving patients with HER2-negative metastatic
breast cancer with a germline BRCA mutation, the median progression-free survival for patients
taking Lynparza was 7 months compared to 4.2 months for patients taking chemotherapy only.

Carboplatin: Prime competitor; organoplatinum compound that possesses antineoplastic activity.

Is a generic prescription.

Carboplatin,
chemical
structure

About 90% of ovarian tumors are epithelial in origin, with the remainder comprising germ and
stromal tumors, and there are three major classified types of ovarian epithelial
adenocarcinomas—serous, mucinous and endometrioid. Chemotherapy plays a major role in the
treatment of patients with advanced ovarian cancer with platinum-based therapies being the
mainstay of first-line treatment.

Immunogen is only public company that is committed to developing an ovarian cancer drug.
IMGN853 has orphan drug designation.
Immunogen is collaborating with Clovic Oncology on the development of the ovarian cancer
treatment; see clinical trial: https://clinicaltrials.gov/ct2/show/NCT03552471
Study is being conducted by Ohio State University Comprehensive Cancer Center
IMGN853 is being tested alongside Rucaparib Camsylate
a potent mammalian poly(ADP-ribose) polymerase (PARP) 1, 2 and 3 inhibitors with anticancer
properties. The indication of rucaparib as an oral monotherapy in patients with deleterious
BRCA mutation (germline and/or somatic) associated advanced ovarian cancer was granted
accelerated approval in 2016 for selected patients who have previously received greater than two
lines of platinum-based therapy. https://www.drugbank.ca/salts/DBSALT001982

CLINICAL TRIAL PHASE 3 ANALYSIS

Official Title: FORWARD I: A Randomized, Open Label Phase 3 Study to Evaluate the Safety
and Efficacy of Mirvetuximab Soravtansine (IMGN853) Versus Investigator's Choice of
Chemotherapy in Women with Folate Receptor Alpha Positive Advanced Epithelial Ovarian
Cancer, Primary Peritoneal Cancer or Fallopian Tube Cancer
Study Type: Interventional (clinical trial)
N = 333 (relatively small for a phase 3, usual minimum is 300 but regardless a small trial)
Randomized; parallel assignment; open lab
Study completion date: February 2019
ARM (A group or subgroup of participants in a clinical trial that receives a
specific intervention/treatment, or no intervention, according to the trial's protocol.)
Two arms in study;
Experimental Arm 1: IMGN853 (mirvetuximab soravtansine) administered at 6 mg/kg AIBW ()
once every three weeks
Experimental Arm 2: Paclitaxel, Pegylated Liposomal Doxorubicin, or Topotecan

Competitor analysis:
Paclitaxel (Taxol) – chemotherapy medication used to treat ovarian cancer; injected
intravenously (IV) and has an albumin-bound formulation. Side effects are very excessive’
includes numbness, marrow suppression, allergic reactions, muscle pains and diarrhea. More
serious side effects include lung inflammation and infection risk. It works by interference with
the normal function of microtubules during cell division. Created in 1971 and approved in 1993.
Economics: Very expensive treatment; as of 2006, the cost per patient in early breast cancer,
assuming four cycles of treatment was about $6000
Available in generic form
Mechanism of action: The ability of paclitaxel to inhibit spindle function is generally attributed
to its suppression of microtubule dynamics, but recent studies have demonstrated that
suppression of dynamics occurs at concentrations lower than those needed to block mitosis. At
the higher therapeutic concentrations, paclitaxel appears to suppress microtubule detachment
from centrosomes, a process normally activated during mitosis. Paclitaxel binds to the beta-
tubulin subunits of microtubules.
Doxorubicin (Pegylated Liposomal Doxorubicin) – a chemotherapy medication used to treat
cancer. This includes breast cancer; given through IV. Is in the anthracycline and antitumor
antibiotic family of medications; work in part by interfering with DNA function. Approved for
use in 1974

Peptide Analog
Look for last publication for the drug apart from the current study;
Biosynthesis; look at biological data; anti-cancer activity of it.

Interesting finding, like many of its cousins that are also monoclonal antibody treatments,
IMGN853 is also one, and all previous big company experimentations with monoclonal antibody
treatments have been very successful, including Pfizer. An antibody is a protein that sticks to a
specific protein called an antigen. Researchers can design antibodies that specifically target a
certain antigen, such as one found on cancer cells. They can then make many copies of that
antibody in the lab. These are known as monoclonal antibodies (mAbs). (cite:
https://www.cancer.org/treatment/treatments-and-side-effects/treatment-
types/immunotherapy/monoclonal-antibodies.html)
“so far mAbs have proven to be more useful against some cancers than others.” Cite: American
Cancer Society.
“Over the past couple of decades, the US Food and Drug Administration (FDA) has approved
more than a dozen mAbs to treat certain cancers.”

The general consensus seems to be that mABs are very effective at treating cancer, and
Immunogen’s ongoing collaborations with big Amgen, Novartis and Sanofi; further confirming
the seriousness of this company, as rarely do large recognized and established pharmaceutical
companies cooperate with much smaller ones.
 Study Analyses

1: Guo Q, Yang Q, Li J, Liu G, Nikoulin I, Jia S. Clinical Trials of Novel

Targeted Therapies in Ovarian Cancer: Moving Beyond Poly ADP Ribose
Polymerase
(PARP) Inhibitors. Curry Pharm Biotechnology. 2018 Dec 26. doi:
10.2174/1389201020666181226123054. [Epub ahead of print] PubMed PMID:
30585545.

Commentary:
Study opens by noting how epithelial ovarian cancer is amongst the most common and deadly
cancers in the female reproductive system, it is very dangerous for women. The scientists note
that recent developments in molecular biology in the development of this cancer have brought
new data demonstrating that Poly-ADP-ribose polymerase inhibitors (PARPi) has been noted as
one of the most successful classes of targeted therapies, already having 3 approved medicines.
The only current available competitor for EOC treatment is bevacizumab plus chemotherapy; it
is the only treatment with current FDA Approval (note that study was done very recently; 2018
end). Implications of ongoing phase 3s include the assumption that mirvetuximab soravtansine
plus chemotherapy will generate positive results to justify its approval. Supports the thesis that
this drug will be successful. HOWEVER, there is a note that observes that targeted therapies
against other growth-related factors, cytokines and folate receptor (IMGN853) are failed in phase
3 or ongoing.

2: Stewart D, Cristea M. Antibody-drug conjugates for ovarian

cancer: current
clinical development. Curr Opin Obstet Gynecol. 2019
Feb;31(1):18-23. doi:
10.1097/GCO.0000000000000515. PubMed PMID: 30531606.

Commentary:
The review of the ADCs demonstrates that this brand new class of drugs utilizes a cytotoxic
mechanism in its treatment of EOC. There are many other companies developing ADCs but
IMGN853 seems to be the most recent and developed one. Stewart and Cristea write that the
antitumor effect is seen primarily in less heavily treated EOC patients (so little prior treatment)
with patients who have moderate to high intensity Fra tumor expression. Antibody drug
conjugates (ADC) are a novel class of cancer therapeutics, delivering cytotoxic therapy directly
to cancer cells, and show promise in the management of platinum-resistant ovarian cancer. The
aim with this treatment is to reduce the off-target toxicity of the delivery of the ADC (the
treatment) while binding the antigens that are overexpressed on the cancer cells.

3: Kaplon H, Reichert JM. Antibodies to watch in 2019. MAbs. 2018 Dec

5. doi:
10.1080/19420862.2018.1556465. [Epub ahead of print] PubMed PMID:
30516432.
Commentary: Direct quote from review paper: “ADC ‘antibodies to watch’ include
mirvetuximab soravtansine (ImmunoGen), trastuzumab duocarmazine (Synthon
BioPharmaceuticals), and depatuxizumab mafodotin (AbbVie). Mirvetuximab soravtansine, an
ADC that targets αfolate receptor 1, is undergoing evaluation in the Phase 3 FORWARD I study
(NCT02631876) of patients with folate receptor alpha-positive advanced epithelial ovarian
cancer, primary peritoneal cancer or fallopian tube cancer.”
Not much actual data being expressed as there is very little actual data being commented on, just
pure speculation on part of the author.

4: Fan CA, Reader J, Roque DM. Review of Immune

Therapies Targeting Ovarian
Cancer. Curr Treat Options Oncol. 2018 Nov
14;19(12):74. doi:
10.1007/s11864-018-0584-3. Review. PubMed PMID:
30430276.

Commentary: Essentially just a review article that summarizes the findings in immunotherapy
based cancer treatments in recent years and any future findings that there might be in the field of
gynecologic malignancies particularly with monoclonal antibodies.

Direct quote from paper: Of note, FRα is also the target for mirvetuximab soravtansine
(IMGN853), a humanized monoclonal antibody attached via a disulfide-containing linker to the
cytotoxic maytansinoid, DM4. Once released within the target cell, DM4 acts as an anti-mitotic
agent that 74 Page 10 of 21 Curr. Treat. Options in Oncol. (2018) 19:74 inhibits tubulin
polymerization and microtubule assembly, resulting in cell cycle arrest and apoptosis. A phase
III study of mirvetuximab soravtansine versus investigator’s choice chemotherapy (paclitaxel,
pegylated liposomal doxorubicin, or topotecan) in platinum-resistant ovarian cancer is currently
ongoing (FORWARD1, NCT02631876) [46]. Mirvetuximab soravtansine is not independently
cytotoxic to FRαnegative endometrial cells in vitro; however, bystander killing on FRα-negative
cells in co-culture with FRαpositive cells does occur [47]. This effect is presumably secondary to
diffusion of metabolites to adjacent cells following lysosomal processing post-internalization
[48]. Thus, antibody-drug conjugation may offer prominent advantages relative to other FRα-
targeting strategies including farletuzumab (MORAb-003; Morphotek, Inc., Exton, PA), which
relies only upon antibodydependent cellular and complement-dependent cytotoxicity.

5: Corbelli E, Miserocchi E, Marchese A, Giuffrè C, Berchicci L, Sacconi R,

Bandello F, Modorati GM. Ocular Toxicity of Mirvetuximab. Cornea. 2019
Feb;38(2):229-232. doi: 10.1097/ICO.0000000000001805. PubMed PMID:
30379722.

Commentary: This study performed by Corbelli et al, had n = 5 patients and the objective was to
measure the ocular toxicity of mirvetuximab soravtansine over a period of 5 months. The trial
was very small, however, the general conclusion gained was that on average, all of the female
patients (between ages 57 and 67) who were being treated for EOC, fallopian tube cancer and
primary peritoneal cancer were affected at least in part in their eyes, as all five had tearing, four
had foreign body sensation, four had photophobia and five had blurred vision. However, the
conclusion was that this downside of the drug was not truly problematic and had little
interference with the primary drug’s involvement, as these side effects were all easily and
quickly cured (full recovery) with the use of topical steroid and lubricants. In relation to the
condition that IMGN853 was attempting to treat in this scenario: In most cases, drug therapy
need not be modified or discontinued, but if visual acuity is affected, close collaboration with the
prescribing physician can result in determining an optimized dose that treats systemic disease
and minimizes these deposits.

6: Vranic S, Palazzo J, Sanati S, Florento E, Contreras E, Xiu J, Swensen

J,
Gatalica Z. Potential Novel Therapy Targets in Neuroendocrine
Carcinomas of the
Breast. Clin Breast Cancer. 2018 Sep 5. pii: S1526-8209(18)30321-5.
doi:
10.1016/j.clbc.2018.09.001. [Epub ahead of print] PubMed PMID:
30268765.

Commentary: Study primarily discusses the treatment of neuroendocrine (NEC) carcinoma of the
breast. A rare, special type of breast cancer, affecting 2% to 5% of breast cancers. There is no
specific targeted therapy for this order. N = 20; the study scanned for biomarkers of therapy
including antibody-drug conjugates (DLL3, TROP-2, and FOLR1), histone deacetylase
(H3K36Me3) inhibitors, tropomyosin receptor kinases (NTRK1/2/3 gene fusions) targeted
inhibitors, alkylating agents (MGMT), and immune checkpoint inhibitors. Investigates the
potential of drugs and there could-be treatment on the follicle receptors (particularly FRa) and
notes that mirvetuximab soravtansine could have a role in the treatment of this disorder, as it fits
the binding requirements.

7: Brand C, Sadique A, Houghton JL, Gangangari K, Ponte JF, Lewis JS,

Pillarsetty
NVK, Konner JA, Reiner T. Leveraging PET to image folate receptor α
therapy of an
antibody-drug conjugate. EJNMMI Res. 2018 Aug 28;8(1):87. doi:
10.1186/s13550-018-0437-x. PubMed PMID: 30155674; PubMed Central
PMCID:
PMC6113196.

Commentary: Study essentially analyzes the humanized anti-body based radiotracer known as
[89Zr]Zr-DFO-M9346A which targets tumor-associated FRa in the preclinical setting. The
objective of this study was to measure a PET imaging agent strategy that would target FRa in
ovarian cancer as a predictor of success. The study concluded that there was a high specificity
for binding FRa positive cells in vitro, as DFO-M9346A was labeled with Zr-89 at 37 °C within
60 min and isolated in labeling yields of 85.7 ± 5.7%, radiochemical purities of 98.0 ± 0.7%, and
specific activities of 3.08 ± 0.43 mCi/mg. The radiotracer demonstrated excellent tumor uptake
for the xenografts (a xenograft is a tissue graft or organ transplant from a donor of a different
species from the recipient.)

8: Moore KN, O'Malley DM, Vergote I, Martin LP, Gonzalez-Martin A,

Malek K,
Birrer MJ. Safety and activity findings from a phase 1b escalation study
of
mirvetuximab soravtansine, a folate receptor alpha (FRα)-targeting
antibody-drug
conjugate (ADC), in combination with carboplatin in patients with
platinum-sensitive ovarian cancer. Gynecol Oncol. 2018 Oct;151(1):46-
52. doi:
10.1016/j.ygyno.2018.07.017. Epub 2018 Aug 6. PubMed PMID:
30093227.

Commentary: It has previously been demonstrated that higher tumor receptor expression is
associated with greater antitumor activity when mirvetuximab soravtansine is administered as
monotherapy
Consistent with this, eight of the responses occurred in the subset of patients with medium/high
FRα expression (n = 10), resulting in an ORR of 80%. 10/18 patients were responsive to
treatment, EOC is a malignancy considered highly receptive to the application of FRα-targeting
therapeutics. The maturing clinical profile of mirvetuximab soravtansine, the first FRα-targeting
ADC, has been characterized by good tolerability and encouraging signs of single-agent
antitumor activity, initially in platinum-resistant EOC. Clinicians in study believe that the
preclinical data demonstrated that IMGN853 has enough potency to be more efficient and
outperform other therapeutic combinations for cancer in combination with carboplatin, as this
drug seems to be the much more efficient performer by comparison. “In preclinical models,
mirvetuximab soravtansine was shown to potentiate the antitumor activity of carboplatin, with
the combination being more active than other clinically relevant modalities
(carboplatin/paclitaxel and carboplatin/PLD).”

********Confirming preclinical expectations, mirvetuximab soravtansine was shown to be a

safe and highly active partnering agent for carboplatin for the treatment of platinum-sensitive
EOC******
This study actually confirms a previous study that found that the administration of mirvetuximab
soravtansine leads to aggressive eye-related side effects, however, that this is typical of
medicines that are meant to treat most ovarian cancers and CAN be combated by administering
topical creams.
*******Indeed, a key finding of the safety analyses was that the tolerability of the
carboplatin/mirvetuximab soravtansine combination was at least equivalent to current standard-
of-care platinum-based chemotherapy.******* Statement demonstrates that even if this drug
does not significantly outperform the current available treatments for EOC, it definitely meets
the current standard for ovarian cancer chemotherapy.
******In stark contrast, no alopecia was observed in any patients receiving
carboplatin/mirvetuximab soravtansine in the present study. Importantly, the combination was
also characterized by a low incidence of potentially dose-limiting toxicities, including
hypersensitivity reactions and peripheral neuropathy, which were similar in frequency and
severity to the profiles seen with either carboplatin/ gemcitabine or carboplatin/PLD therapy, and
well below levels observed with carboplatin/paclitaxel treatment [8,9,11]. With specific respect
to hypersensitivity, only three patients overall (17%) experienced infusion related reactions in
the current study, all of which were mild (grade 2). Importantly, none of these events were
considered dose-limiting or reached seriousness criteria, even in the two instances where they led
to carboplatin discontinuation.******
2-28-19

After further analysis, it seems that Immunogen has made the decision to delay their
announcement and completion of their main phase 3 trial for Mirvetuximab Soravtansine in
treatment of ptobum resistant epithelial ovarian cancer all the way to June 2019. The granting of
a fast track designation to this treatment by the FDA, however, provides further hope that this
will be a successful drug. Still developing ongoing analysis of the treatment in comparison to
already available and approved mono therapies, as well as carboplatin based adjunct therapies.

3-1-19

Personal Notes: Immunogen announced results from study; mirvetuximab soravtansine was a
failure in its approval. Trial did NOT meet its primary endpoint of progression-free survival. The
failure of this folate receptor alpha targeting anti body conjugate failing tells of the future for
drugs with this particular mechanism of action. The given failure of the drug, along with the
most significant studies related to this product being simple review papers that only provided for
speculation on this drug and its potential effects was indicative of its failure. This paper was
written progressively over time and was connected to a financial analysis of this company. My
own personal position involved a call option expiring in March, all in projection of the main
clinical trial phase 3 results being announced in late February. Throughout my analysis I called
Immunogen a total of 17 times over a 1 week period, even calling 5 times within an hour and
having my calls unanswered as well as a message I left for a worker in the reception. The paper
written on the ocular side effects of this treatment for epithelial ovarian cancer was particularly
concerning as it only analyzed 5 patients which created a worry for me. The online community in
support of this treatment seemed to have been based on technical analysis, advocating for the
company’s success based on moving average calculations and cyclical price tendencies, rather
than focusing on the efficacy of a heavily invested-in treatment, another thing that concerned me
when I was analyzing this treatment. On my own time, my interactions with professionals in this
particular field led to conclusions that demonstrated that this treatment would not be successful,
as its phase 2 results were mediocre at best and their professional opinion was primarily
negative, with these professionals expressing that the best result that could come from this
clinical trial was that the drug would be approved, but would at best be as effective or less
effective as the currently approved treatments (paclitaxel, topotecan, pegylated liposomal
doxorubicin), like those related with carboplatin adjunct therapy. Overall the consensus on this
treatment from a medicinal perspective was negative, however, the communal aspect and the
investor confidence seemed high because of the heavy speculation that was involved in a
seemingly revolutionary antibody drug conjugate. I did not begin my analysis in enough time to
cover all facets and because of this I was only able to review half of the papers that I was aiming
to analyze, however, I will not finish my analysis, as the results from the phase 3 FORWARD I
study have spoken for me. The higher response rate for mirvetuximab soravtansine compared to
chemotherapy did not have statistical significance and failed to meet the primary endpoint of the
study and the overall survival rate. Despite the overall failure to meet endpoints, from a clinical
perspective the drug still seems to give hope to patients with epithelial ovarian cancer, as in the
subset of patients who had a high folate receptor alpha expression, there was enough positive
reaction to create further interest in studying this drug for those particular individuals. From a
safety perspective, mirvetuximab soravtansine seems to be relatively safe with the drug
triggering the most common side effects associated with typical chemotherapy. Analyzing the
finances of the operation, Immunogen still holds a solidified fiduciary position with nearly $300
million in cash in order to pursue further developments in ADC based pharmacology.
References:

Fan, C., Reader, J. and Roque, D. (2018). Review of Immune Therapies Targeting
Ovarian Cancer. Current Treatment Options in Oncology, 19(12).

Kaplon, H. and Reichert, J. (2018). Antibodies to watch in 2019. mAbs, 11(2), pp.219-
238.
Matulonis, U., Birrer, M., O’Malley, D., Moore, K., Konner, J., Gilbert, L., Martin, L.,
Bauer, T., Oza, A., Malek, K., Pinkas, J. and Kim, S. (2018). Evaluation of Prophylactic
Corticosteroid Eye Drop Use in the Management of Corneal Abnormalities Induced by the
Antibody–Drug Conjugate Mirvetuximab Soravtansine. Clinical Cancer Research.

Corbelli, E., Miserocchi, E., Marchese, A., Giuffrè, C., Berchicci, L., Sacconi, R.,
Bandello, F. and Modorati, G. (2018). Ocular Toxicity of Mirvetuximab. Cornea, p.1.

Stewart, D. and Cristea, M. (2019). Antibody–drug conjugates for ovarian

cancer. Current Opinion in Obstetrics and Gynecology, 31(1), pp.18-23.

Matulonis, U., Moore, K., Martin, L., Vergote, I., Castro, C., Gilbert, L., Berkenblit, A.,
Birrer, M. and O'Malley, D. (2018). Initial safety and activity findings from a phase IB
escalation study of mirvetuximab soravtansine, a folate receptor alpha (FRα-targeting antibody-
drug conjugate (ADC), with pembrolizumab in platinum-resistant epithelial ovarian cancer
(EOC) patients. Gynecologic Oncology, 149, p.38.

Vranic, S., Palazzo, J., Sanati, S., Florento, E., Contreras, E., Xiu, J., Swensen, J. and
Gatalica, Z. (2018). Potential Novel Therapy Targets in Neuroendocrine Carcinomas of the
Breast. Clinical Breast Cancer.
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(2016). Targeting folate receptor alpha for cancer treatment. Oncotarget, 7(32).

En.wikipedia.org. (2019). Farletuzumab. [online] Available at:

https://en.wikipedia.org/wiki/Farletuzumab [Accessed 2 Mar. 2019].

Hopp, E., Joseph, P., Nakayama, J., Zanotti, K., Nagel, C., Waggoner, S. and DiFeo, A.
(2018). Identifying susceptibilities and pharmacodynamic biomarkers for mirvetuximab
soravtansine in high-grade ovarian and endometrial cancer. Gynecologic Oncology, 149, p.57.
 En.wikipedia.org. (2019). ImmunoGen. [online] Available at:
https://en.wikipedia.org/wiki/ImmunoGen#Pipeline [Accessed 2 Mar. 2019].

Matulonis, U., Moore, K., Martin, L., Vergote, I., Castro, C., Gilbert, L., Berkenblit, A.,
Birrer, M. and O'Malley, D. (2018). Initial safety and activity findings from a phase IB
escalation study of mirvetuximab soravtansine, a folate receptor alpha (FRα-targeting antibody-
drug conjugate (ADC), with pembrolizumab in platinum-resistant epithelial ovarian cancer
(EOC) patients. Gynecologic Oncology, 149, p.38.

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