TH-302 (HAP)

TH-CR-403

TH-CR-402 is a randomized Phase 1/2 dose escalation trial that will evaluate efficacy and safety of TH-302 in patients with advanced solid tumors. Approximately 36 patients with metastatic and/or advanced unresectable soft tissue sarcoma are planned to enroll in the clinical trial at various sites in the United States. The dose escalation phase of the trial will enroll up to 24 patients. The primary objective of the dose escalation component of the study is to establish the maximum tolerated dose (MTD) and dose limiting toxicities of TH-302 in combination with doxorubicin. Patients for whom no effective therapy is available or for whom monotherapy with doxorubicin is considered standard therapy are eligible for the trial. Patients who successfully complete one treatment cycle without evidence of significant treatment-related toxicity or progressive disease may continue to receive treatment for up to six cycles.

Once the MTD has been reached, the Phase 2 portion of the trial will enroll an additional 12 patients at the MTD. The primary objective of the dose expansion component of the study is to make a preliminary assessment of the efficacy of TH-302 in combination with doxorubicin as measured by the progression-free rate at 6 months in patients previously untreated with chemotherapy.

The secondary endpoints of the trial include response, duration of response, progression-free rate at 3 months, progression-free survival, overall survival and various safety parameters. Tumor response will be evaluated at baseline and every six weeks using the Response Evaluation Criteria In Solid Tumors (RECIST).

For further information on the TH-CR-403 study or to find a clinical trial site nearest you, please contact the Threshold Pharmaceuticals clinical trials group at 1-650-474-8222 or email us at clinicaltrials@thresholdpharm.com. Alternatively, this clinical trial can be found at the ClinicalTrials.gov website.

TH-CR-402

TH-CR-402 is a randomized Phase 1/2 dose escalation trial that will evaluate efficacy and safety of TH-302 in patients with advanced solid tumors. Approximately 50 patients with advanced solid tumors are planned to enroll in the Phase 1, dose escalation portion of the clinical trial. The initial dose of TH-302 will be 240mg/m2 which is the highest dose with no study drug-related grade 2 or greater toxicity in the currently ongoing Phase 1 trial of TH-302. Up to six patients per dose level will participate in the dose escalation phase of the trial. Once the maximum tolerated dose (MTD) has been reached, the Phase 2 portion of the trial will enroll an additional 12 patients at the MTD within each treatment arm as follows: gemcitabine in advanced pancreatic cancer patients, docetaxel in patients with castrate-resistant prostate cancer (CRPC) and pemetrexed in patients with non-small cell lung cancer.

TH-302 will be administered as a 30-minute intravenous infusion weekly for three weeks followed by one week off therapy in the gemcitabine arm, and weekly for two weeks followed by one week off therapy in the docetaxel and pemetrexed arms. Patients for whom no effective therapy is available or for whom monotherapy with one of the chemotherapy regimens is considered standard therapy, are eligible for the trial. Patients who successfully complete one treatment cycle without evidence of significant treatment-related toxicity or progressive disease will continue to receive treatment for up to six cycles (eight cycles for prostate cancer).

The primary objectives of the study are to determine the MTD and dose-limiting toxicities of TH-302 when used in combination with gemcitabine or docetaxel or pemetrexed in patients with advanced solid tumors and to assess the safety of TH-302 in these combination regimens. The primary objective of the dose expansion phase of the trial is to make a preliminary assessment of the efficacy of TH-302 based on tumor response rate and progression-free survival. Secondary objectives include establishing the pharmacokinetics and making a preliminary assessment of efficacy based on serum tumor markers of TH-302 when used in combination with gemcitabine, docetaxel or pemetrexed.

For further information on the TH-CR-402 study or to find a clinical trial site nearest you, please contact the Threshold Pharmaceuticals clinical trials group at 1-650-474-8222 or email us at clinicaltrials@thresholdpharm.com. Alternatively, this clinical trial can be found at the ClinicalTrials.gov website.

TH-CR-401

TH-CR-401 is a randomized Phase 1 dose escalation trial that will evaluate efficacy and safety of TH-302 in patients with advanced solid tumors. Approximately 50 patients with advanced solid tumors are planned to enroll in the trial that is being conducted in the United States. Up to six patients per dose level will participate in the dose escalation phase of the trial. Once a maximum tolerated dose (MTD) has been established, six additional patients will be enrolled at the MTD level.

TH-302 is administered as a 30-minute intravenous infusion weekly for three weeks followed by one week off therapy. Patients who have received one or more regimens of chemotherapy, or for whom no effective therapy is available, are eligible for the trial. Patients will not receive any additional chemotherapy while receiving TH-302. Patients who successfully complete a four week treatment cycle without evidence of significant treatment-related toxicity or progressive disease will continue to receive treatment for up to six cycles. Tumor response will be measured at the end of cycles 2, 4 and 6.

Who Can Participate?

Selected Inclusion Criteria:

In order to participate in this study, a person must meet the following criteria:

• Males and females, at least 18 years of age
• Histologically confirmed, locally advanced or metastatic solid malignancy
• Previously treated with at least one chemotherapy regimen for advanced or metastatic disease OR no curative standard treatment is available
• Recovered from reversible toxicities of prior therapy
• Measureable disease by RECIST (at least one target lesion)

Selected Exclusion Criteria:

• Symptomatic brain metastases (screening CT or MRI is not required in asymptomatic subjects)
• Active clinically significant infection requiring antibiotics
• History or symptoms of cardiovascular disease particularly coronary artery disease, unstable arrhythmias, or myocardial infarction within the last 6 months
• Known HIV infection, hepatitis B or hepatitis C
• Other primary malignancies (other than treated basal cell carcinoma of the skin or treated in situ cervical cancer) within the past 5 years
• Major surgery within 4 weeks of the start of study treatment, without complete recovery
• Antitumor therapy within 4 weeks of the start of study treatment
• Participation in an investigational drug or device study within 28 days of the first day of dosing on this study

Please note there are other additional criteria. The study center will determine if you meet all of the requirements for enrollment.

For further information on the TH-CR-401 study or to find a clinical trial site nearest you, please contact the Threshold Pharmaceuticals clinical trials group at 1-650-474-8221 or email us at clinicaltrials@thresholdpharm.com. Alternatively, this clinical trial can be found at the ClinicalTrials.gov website.

2-Deoxyglucose (2DG)

TH-CR-101

TH-CR-101 is a randomized Phase 1 dose escalation trial that evaluated efficacy and safety of 2-Deoxyglucose (2DG) in combination with docetaxel in patients with advanced solid tumors. Patients participated in the study for up to 53 weeks.

The trial was conducted at the following locations:

• UM Sylvester Comprehensive Cancer Center, Miami, FL
• Cancer Therapy and Research Center (CTRC), San Antonio, TX
• Indiana University Cancer Center, Indianapolis, Indiana
• Cancer Institute of New Jersey, New Brunswick, NJ

This trial is closed to enrollment and is completed.

For further information on the TH-CR-101 study, please contact the Threshold Pharmaceuticals clinical trials group at 1-650-474-8228 or email us at clinicaltrials@thresholdpharm.com.