CAMBRIDGE, Mass.--(BUSINESS WIRE)--Sesen Bio, Inc. (Nasdaq: SESN), a late-stage clinical company advancing targeted fusion protein therapeutics for the treatment of cancer, today reported positive preliminary efficacy data for the primary endpoint of its ongoing Phase 3 registration trial, the VISTA Trial, of Vicinium® for the treatment of patients with high-grade non-muscle invasive bladder cancer (NMIBC) who have been previously treated with bacillus Calmette-Guérin (BCG) and deemed BCG-unresponsive. The data reported show clinically meaningful complete response rates in evaluable Carcinoma in situ patients at three, six, nine and 12 months of follow-up in the trial consistent with the data in the completed Phase 1 and Phase 2 clinical trials. Importantly, Vicinium continues to be generally well-tolerated in treated patients.
“Non-muscle invasive bladder cancer is a very prevalent cancer that can progress to become incurable. The usual treatment for patients who relapse or become refractory to BCG, today’s standard-of-care, is complete bladder removal or radical cystectomy,” said Michael A.S. Jewett, M.D., Professor of Surgery, Division of Urology, University of Toronto. “Removing the bladder is a potentially morbid and complex surgery with potential for side effects that can drastically reduce a patient’s quality of life. In fact, many patients choose not to undergo bladder removal. I am very encouraged by the data generated to-date with intravesical Vicinium as an alternative after BCG failure. Based on the strength of the clinical activity observed, and the consistently favorable safety and tolerability, I believe that Vicinium has the potential to change the treatment outcome for patients.”
VISTA Trial Design
The Phase 3 VISTA Trial is a
single-arm, multi-center clinical trial designed to support the approval
of Vicinium for the treatment of patients with high-grade,
BCG-unresponsive NMIBC. The trial enrolled a total of 133 patients
across three cohorts based on histology and time to disease recurrence
after adequate BCG:
- Cohort 1 (n=86): Carcinoma in situ patients with or without papillary disease whose cancer was determined to be refractory or recurred within six months of their last course of adequate BCG
- Cohort 2 (n=7): Carcinoma in situ patients with or without papillary disease whose cancer was determined to be refractory or recurred after six months, but less than 12 months, after their last course of adequate BCG
- Cohort 3 (n=40): patients with papillary disease without Carcinoma in situ whose cancer was determined to be refractory or recurred within six months of their last course of adequate BCG
The data reported build upon preliminary three-month data presented from a subset of patients in May 2018 and are for the primary endpoint of the VISTA Trial, which is the complete response rate and duration of response in patients in Cohort 1. The company also reported data from Cohort 2, separately and pooled with Cohort 1, based on final U.S. Food and Drug Administration guidance on treatment of BCG-unresponsive Carcinoma in situ patients (defined as patients with recurrent Carcinoma in situ within 12 months of adequate BCG therapy)1.
The patient population in Cohort 3 represents an opportunity for future label expansion, and the company plans to report efficacy data from this cohort, as well as the secondary endpoints in the VISTA Trial, in mid-2019.
Preliminary Efficacy Results in Carcinoma in situ Patients
|
Cohort 1 (n=86) |
||||||||||
| Time point | Evaluable Patients | Complete Response Rate (95% Confidence Interval) | ||||||||
| 3-months | n=86 | 37% (27%, 48%) | ||||||||
| 6-months | n=85 | 25% (16%, 35%) | ||||||||
| 9-months | n=84 | 18% (10%, 28%) | ||||||||
| 12-months | n=81 | 14% (7%, 23%) | ||||||||
|
Cohort 2 (n=7) |
||||||||||
| Time point | Evaluable Patients | Complete Response Rate (95% Confidence Interval) | ||||||||
| 3-months | n=7 | 57% (18%, 90%) | ||||||||
| 6-months | n=7 | 57% (18%, 90%) | ||||||||
| 9-months | n=7 | 43% (10%, 82%) | ||||||||
| 12-months | n=7 | 14% (0%, 58%) | ||||||||
|
Pooled Cohorts 1 and 2 (n=93) |
||||||||||
| Time point | Evaluable Patients | Complete Response Rate (95% Confidence Interval) | ||||||||
| 3-months | n=93 | 39% (29%, 49%) | ||||||||
| 6-months | n=92 | 27% (18%, 37%) | ||||||||
| 9-months | n=91 | 20% (12%, 29%) | ||||||||
| 12-months | n=88 | 14% (7%, 23%) | ||||||||
Notably, the interim Phase 3 complete response rates in pooled patients from Cohorts 1 and 2 are in-line with the complete response rates in pooled patients in the completed Phase 2 clinical trial.
|
Preliminary Phase 3 CRR vs Phase 2 CRR |
||||||||||
| Time point |
Phase 3 Pooled CRR
(95% Confidence Intervals) |
Phase 2 Pooled CRR
(95% Confidence Interval) |
||||||||
| 3-months | 39% (29%, 49%) | 40% (26%, 56%) | ||||||||
| 6-months | 27% (18%, 37%) | 27% (15%, 42%) | ||||||||
| 9-months | 20% (12%, 29%) | 18% (8%, 32%) | ||||||||
| 12-months | 14% (7%, 23%) | 16% (7%, 30%) | ||||||||
The company also reported an update on the durability of responses in the VISTA Trial. While the median has not yet been reached, the preliminary data show that Vicinium treatment resulted in a prolonged duration of response in many patients. This is particularly notable given that, in order for patients to remain on study, they have to have achieved a complete response at each assessment time period. These findings suggest that Vicinium has the potential to benefit patients by delaying the time to a radical cystectomy, a secondary endpoint that will be measured and reported in mid-2019.
Preliminary Safety Results
Vicinium continues to be
well-tolerated by patients treated in the VISTA Trial. As of the
December 3, 2018 data cut off, in patients across all three cohorts
(n=133), 78 percent of adverse events were Grade 1 or 2. The most
commonly reported treatment-related adverse events were dysuria (13%),
hematuria (12%) and urinary tract infection (11%) – all of which are
consistent with the profile of bladder cancer patients and the use of
catheterization for treatment delivery. These adverse events were
determined to be manageable and reversible, and only five patients
discontinued treatment due to an adverse event. Serious adverse events,
regardless of treatment attribution, were reported in 14 percent of
patients. There were four treatment-related SAEs reported in three
patients including acute renal injury (Grade 3), pyrexia (Grade 2),
cholestatic hepatitis (Grade 4) and renal failure (Grade 5).
“We are very pleased with these preliminary data, which are consistent with the data in our completed Phase 2 clinical trial of Vicinium for the treatment of high-grade NMIBC, and further support our belief that Vicinium has the potential to change how patients are treated after BCG,” said Dr. Thomas Cannell, president and chief executive officer of Sesen Bio. “The design of the VISTA Trial aligns with FDA’s guidance for NMIBC drug development, and the findings are highly encouraging, demonstrating that treatment with Vicinium results in clinically meaningful efficacy and favorable safety and tolerability. Overall, the data reinforce our belief that Vicinium is positioned to provide a valuable benefit to patients by treating their disease with long-term responses and extending their time to face such a decision as removing their bladder. 2019 is set to be a transformational year for Sesen Bio, and we look forward to advancing the VISTA Trial and assessing the full 12-month data from all patients later this year.”
The VISTA Trial completed enrollment in the second quarter of 2018, and complete 12-month efficacy data from all patients in the clinical trial are expected to be reported at a medical meeting in mid-2019.
Conference Call Information
To participate in the conference
call, please dial (844) 831-3025 (domestic) or (315) 625-6887
(international) and refer to conference ID 4263106. The webcast can be
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The replay of the webcast will be available in the investor section of
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for 60 days following the call.
About the VISTA Clinical Trial
The VISTA Trial is an
open-label, multicenter, single-arm Phase 3 clinical trial evaluating
the efficacy and tolerability of Vicinium® in patients with
high-grade non-muscle invasive bladder cancer (NMIBC) that is Carcinoma in
situ, which is cancer found on the inner lining of the bladder that
has not spread into muscle or other tissue and/or papillary, which is
cancer that has grown from the bladder lining out into the bladder but
has not spread into muscle or other tissue, who have been previously
treated with bacillus Calmette-Guérin (BCG). The primary endpoint of the
trial is the complete response rate in patients with Carcinoma in situ
with or without papillary disease. Patients in the trial receive locally
administered Vicinium twice a week for six weeks, followed by
once-weekly treatment for another six weeks, then treatment every other
week for up to two years. Twelve-month data from all patients in the
VISTA Trial are anticipated in mid-2019. To learn more about the Phase 3
VISTA Trial, please visit www.clinicaltrials.gov and
search the identifier NCT02449239.
About Vicinium®
Vicinium®, a
locally-administered fusion protein, is Sesen Bio’s lead product
candidate being developed for the treatment of high-grade non-muscle
invasive bladder cancer (NMIBC). Vicinium is comprised of a recombinant
fusion protein that targets epithelial cell adhesion molecule (EpCAM)
antigens on the surface of tumor cells to deliver a potent protein
payload, Pseudomonas Exotoxin A (ETA). Vicinium is constructed
with a stable, genetically engineered peptide tether to ensure the
payload remains attached until it is internalized by the cancer cell,
which is believed to decrease the risk of toxicity to healthy tissues,
thereby improving its safety. In prior clinical trials conducted by
Sesen Bio, EpCAM has been shown to be overexpressed in NMIBC cells with
minimal to no EpCAM expression observed on normal bladder cells. Sesen
Bio is currently conducting the Phase 3 VISTA Trial, designed to support
the registration of Vicinium for the treatment of high-grade NMIBC in
patients who have previously received two courses of bacillus
Calmette-Guérin (BCG) and whose disease is now BCG-unresponsive.
Complete twelve-month data from the trial are anticipated in mid-2019.
Additionally, Sesen Bio believes that Vicinium’s cancer cell-killing
properties promote an anti-tumor immune response that may potentially
combine well with immuno-oncology drugs, such as checkpoint inhibitors.
The activity of Vicinium in BCG-unresponsive NMIBC is also being
explored at the US National Cancer Institute in combination with
AstraZeneca’s immune checkpoint inhibitor durvalumab.
About Non-Muscle Invasive Bladder Cancer
Bladder cancer is
the sixth most commonly diagnosed cancer in the United States, and
approximately 80 percent of patients have non-muscle invasive bladder
cancer (NMIBC). In NMIBC, cancer cells are in the lining of the bladder
or have grown into the lumen of the bladder but have not spread into
muscle or other tissue. NMIBC primarily affects men and is associated
with carcinogen exposure. Initial treatment includes surgical resection;
however, there is a high rate of recurrence and more than 60 percent of
all patients diagnosed with NMIBC will receive bacillus Calmette-Guérin
(BCG) immunotherapy. While BCG is effective in many patients, challenges
with tolerability have been observed and many patients will experience
recurrence of disease. If BCG is not effective or a patient can longer
receive BCG, the recommended option for treatment is radical cystectomy,
the complete removal of the bladder.
About Sesen Bio
Sesen Bio, Inc. is a late-stage clinical
company advancing targeted fusion protein therapeutics for the treatment
of cancer. The company’s lead program, Vicinium®, also known
as VB4-845, is currently in a Phase 3 registration trial, the VISTA
Trial, for the treatment of high-grade, BCG-unresponsive non-muscle
invasive bladder cancer. Twelve-month data from all patients in the
VISTA Trial are anticipated in mid-2019. Vicinium incorporates a
tumor-targeting antibody fragment and a protein cytotoxic payload into a
single protein molecule designed to selectively and effectively kill
cancer cells while sparing healthy cells. For more information, please
visit the company’s website at www.sesenbio.com.
Cautionary Note on Forward-Looking Statements
Any statements
in this press release about future expectations, plans and prospects for
the Company, the Company’s strategy, future operations, and other
statements containing the words “anticipate,” “believe,” “estimate,”
“expect,” “intend,” “may,” “plan,” “predict,” “project,” “target,”
“potential,” “will,” “would,” “could,” “should,” “continue,” and similar
expressions, constitute forward-looking statements within the meaning of
The Private Securities Litigation Reform Act of 1995. Actual results may
differ materially from those indicated by such forward-looking
statements as a result of various important factors, including: the
uncertainties inherent in the initiation and conduct of clinical trials,
the possibility that the available preliminary data of the Phase 3 VISTA
Trial are not indicative of final data from all patients in Phase 3
VISTA Trial and final data may not be positive with regard to the safety
or efficacy of Vicinium, our ability to successfully develop our product
candidates and complete our planned clinical programs, our ability to
obtain marketing approvals for our product candidates, expectations
regarding our ongoing clinical trials, availability and timing of data
from clinical trials, the adequacy of any clinical models, expectations
regarding regulatory approvals and other factors discussed in the “Risk
Factors” section of the Company’s Annual Report on Form 10-K, Quarterly
Reports on Form 10-Q and other reports filed with the Securities and
Exchange Commission. In addition, the forward-looking statements
included in this press release represent the Company’s views as of the
date hereof. The Company anticipates that subsequent events and
developments will cause the Company’s views to change. However, while
the Company may elect to update these forward-looking statements at some
point in the future, the Company specifically disclaims any obligation
to do so. These forward-looking statements should not be relied upon as
representing the Company’s views as of any date subsequent to the date
hereof.
1 United States Food and Drug Administration, BCG-Unresponsive Nonmuscle Invasive Bladder Cancer: Developing Drugs and Biologics for Treatment Guidance for Industry, February 2018
