The GALAXY program in lung cancer
At the 2013
“We are very pleased by the reception at the WCLC meeting to the updated
GALAXY-1 results,” said Dr.
Highlights from the recently presented results include:
- Continued confirmation of clinical activity in the prospectively defined chemosensitive patient population selected last year for evaluation in the ongoing GALAXY-2 Phase 3 trial.
- Patients enrolled into the GALAXY-1 trial were prospectively stratified into refractory vs. chemosensitive populations based on the rate of their disease progression during or following first-line treatment for advanced NSCLC (time since diagnosis of advanced disease less than vs. greater than six months).
- In the chemosensitive population (N=178), median overall survival (OS) increased from 7.4 to 10.7 months in patients treated with D vs. G+D arms, respectively. The Hazard ratio was 0.75 (p=0.065) and 0.72 (p=0.04), in the Cox proportional hazards univariate (unadjusted) and multivariate (adjusted) models, respectively. Median progression-free survival (PFS) improved from 3.4 months to 5.3 months, in the D vs. G+D arms, respectively, with Hazard ratios of 0.73 (p=0.031) and 0.72 (p=0.03) in the univariate and multivariate models, respectively. All p-values are 1-sided.
- In the refractory population (N=75), which progressed rapidly on or shortly after first-line chemotherapy, no benefit was observed. These results are consistent with results from other clinical trials showing little to no benefit from second-line treatment for patients with rapidly progressing disease, and from preclinical studies showing that the chemosensitizing mechanism of action of ganetespib may be most effective in chemosensitive cancers.
- A favorable safety profile was observed with the G plus D combination in adenocarcinoma patients. Transient, mild-to-moderate diarrhea, generally manageable with over-the-counter medication, was the most common adverse event, consistent with observations from other clinical trials evaluating ganetespib. Other adverse events increased relative to control included mild to moderate anemia and fatigue, as well as an increase in the number of cases of febrile neutropenia.
- Analysis of data to date revealed that medical profiles from certain patients enrolled from two Eastern European countries differed from patterns typical of patients enrolled from other countries in this study, as well as patients enrolled in other clinical trials for the treatment of advanced second-line NSCLC. This observation informed the operational plan for the ongoing GALAXY-2 Phase 3 trial, including the decision to limit further enrollment from these two countries.
Synta expects final overall survival results from GALAXY-1 by early 2014.
The GALAXY-2 protocol specifies that trial size and statistical assumptions may be updated based on results from GALAXY-1. Based on the near-final results from GALAXY-1, Synta intends to review with lead investigators plans for increasing the GALAXY-2 trial size from 500 patients to 700 patients. This change is intended to decrease the risk from imbalances or statistical fluctuations.
Enrollment of GALAXY-2 began in April 2013. Assuming an increased trial size of 700 patients, Synta expects that interim analyses for GALAXY-2 would be conducted in the second half of 2014, and the final analysis would be conducted in the first half of 2015.
The ENCHANT program in breast cancer
Based on the encouraging results in HER2-positive and triple-negative breast cancer patients, the trial was expanded to add a third cohort, evaluating ganetespib monotherapy for the treatment of patients with hormone receptor-positive disease.
Synta expects initial results from ENCHANT-1 will be presented at the San Antonio Breast Cancer Symposium in December of this year.
Other clinical trials with ganetespib
A number of investigator and cooperative group-sponsored trials with
ganetespib recently initiated or are expected to initiate by end of this
year, including a trial evaluating ganetespib in combination with
pemetrexed and cisplatin in patients with malignant pleural
mesothelioma, being sponsored by
HDCs are drug candiates consisting of an Hsp90 inhibitor (targeting moiety) joined to an anti-cancer agent (payload) via a cleavable chemical linker optimized for controlled release of payload drug inside cancer cells. Because HDCs are small molecules, they diffuse into the cell passively, avoiding reliance on cell surface antigens or transporters, as is required by other delivery mechanisms such as antibody-drug conjugates (ADCs).
The longer retention of Hsp90 inhibitors in tumors results in higher concentration and longer duration of active payload drug inside cancer cells than occurs with standard administration of unconjugated chemotherapy or other payloads. This enhanced delivery creates the potential for greater cancer cell killing and reduced side effects.
Synta has developed over 400 HD-Conjugated chemotherapeutics, kinase inhibitors, hormone therapies, immunomodulators, and epigenetic modifiers, creating the potential for next-generation compounds in each of these categories. Examples include HD-Conjugated bendamustine, temozolomide, doxorubicin, 5-FU, pemetrexed, SN-38, topotecan, vorinostat, panobinostat, fulvestrant, abiraterone, lenalidomide, pomalidomide, docetaxel, carboplatin, bortezomib, sunitinib, and sorafenib.
Proof-of-concept has been established in preclinical models of cancer. HDC improved delivery of SN-38 anti-cancer payload, achieving over thirty times the concentration of this cytotoxic agent in tumor as compared to the concentration in plasma and other tissues. Strongly enhanced anti-tumor activity was seen with the HD-Conjugate as compared to the commonly used SN-38 prodrug, irinotecan, in a broad range of animal models of cancer, including breast cancer, colon cancer, ovarian cancer, small cell lung cancer, bladder cancer, and melanoma.
“We are excited by the progress we have made this past quarter both with
our ganetespib program and with our HDC program,” said Dr.
There were no revenues recognized in the third quarters of 2013 and 2012.
Research and development expenses were
The Company reported a net loss of
More detailed financial information and analysis may be found in the
Company's Quarterly Report on Form 10-Q, which was filed with the
Based on our current operating levels the Company expects its cash
resources of approximately
Management will host a conference call and webcast at
The conference call can be accessed by dialing (877) 407-8035 (U.S.) or
(201) 689-8035 (International). For those unable to join the live call,
a replay will be available from
The live webcast
can be accessed by visiting the Investor
Relations section of the
Ganetespib, an investigational drug candidate, is a selective inhibitor
of heat shock protein 90 (Hsp90), a molecular chaperone which controls
the folding and activation of a number of client proteins that drive
tumor development and progression. Many solid and hematologic tumors are
dependent on Hsp90 client proteins including proteins involved in
“oncogene addiction” (ALK, HER2, mutant BRAF and EGFR, androgen
receptor, estrogen receptor, JAK2); proteins involved in resistance to
chemotherapy and radiation therapy (ATR, BCL2, BRCA1/2, CDK1/4, CHK1,
survivin, and WEE1); proteins involved in angiogenesis (HIF-1alpha,
VEGFR, PDFGR, and VEGF); and proteins involved in metastasis (MET, RAF,
AKT, MMPs, HIF-1alpha, and IGF-1R). In preclinical models, inhibition of
Hsp90 by ganetespib results in the inactivation, destabilization, and
eventual degradation of these cancer-promoting proteins. Ganetespib is
being evaluated in trials in lung cancer, breast cancer, and other tumor
types. The most common adverse event seen to date has been transient,
mild or moderate diarrhea, which has been manageable with standard
supportive care. Information on these trials can be found at www.clinicaltrials.gov.
Ganetespib has received Fast Track designation from
About the GALAXY Program
The GALAXY (Ganetespib Assessment in Lung cAncer with docetaXel) program consists of two randomized trials comparing the combination of ganetespib and docetaxel versus docetaxel alone in patients with Stage IIIB/IV NSCLC who have received one prior systemic therapy: a Phase 2b/3 trial (GALAXY-1) to determine the patient population most likely to derive benefit from ganetespib, and a confirmatory Phase 3 trial (GALAXY-2). More information about the GALAXY trials can be found at www.clinicaltrials.gov (NCT01348126 and NCT01798485).
About the ENCHANT-1 Clinical Trial
ENCHANT-1 is a proof-of-concept trial designed to evaluate single-agent ganetespib safety and clinical activity in patients with locally advanced or metastatic breast cancer. The trial will also evaluate the combination of ganetespib with paclitaxel. More information about this trial can be found at www.clinicaltrials.gov. (NCT01677455)
About Lung Cancer
Lung cancer is the leading cause of cancer-related death in the world,
accounting for nearly 1.4 million deaths in 2008, according to the
About Breast Cancer
Breast cancer is the most frequent cancer in women, accounting for
458,000 deaths worldwide in 2008, according to the
Safe Harbor Statement
This media release may contain forward-looking statements about
|Synta Pharmaceuticals Corp.|
|Condensed Consolidated Statements of Operations|
|(in thousands, except share and per share amounts)|
Three Months Ended
Nine Months Ended
|Research and development||17,623||11,743||51,879||35,061|
General and administrative
|Total operating expenses||21,794||14,539||64,115||43,385|
|Loss from operations||(21,794||)||(14,539||)||(64,115||)||(43,238||)|
|Interest expense, net||(721||)||(457||)||(1,915||)||(1,429||)|
|Basic and diluted net loss per common share||$||(0.33||)||$||(0.25||)||$||(0.96||)||$||(0.77||)|
Basic and diluted weighted average number of
|common shares outstanding||69,047,161||60,661,720||69,024,656||58,235,263|
|Synta Pharmaceuticals Corp.|
|Condensed Consolidated Balance Sheets Data|
|Cash, cash equivalents and marketable securities||$||53,384||$||100,599|
|Other current assets||1,358||786|
|Property, plant and equipment, net||1,488||1,174|
|Other non-current assets||433||458|
|Liabilities and Equity|
|Total liabilities and|