Sponsor: Roswell Park Cancer Institute (other)
Phase: 2
Start date: Jan. 11, 2024
Planned enrollment: 60
SVN53-67/M57-KLH (SurVaxM; DRU-2017-5947) is a survivin-targeted, KLH-conjugated long‑peptide cancer vaccine being investigated primarily for glioblastoma. Survivin is an inhibitor‑of‑apoptosis protein overexpressed in most glioblastomas and many other tumors. Clinical experience to date includes a multicenter, single‑arm phase IIa study in newly diagnosed glioblastoma and an earlier phase I study in recurrent malignant glioma; a randomized phase 2b trial in newly diagnosed glioblastoma is ongoing. (pmc.ncbi.nlm.nih.gov)
Notes: The phase IIa study was single‑arm and compared with historical benchmarks; definitive comparative efficacy awaits randomized readout. (pmc.ncbi.nlm.nih.gov)
Links above point to journals, PubMed/PMC entries, or academic conference/center pages with additional methodological and outcome details.
Last updated: Oct 2025
Goal: To evaluate whether adding the survivin-targeted vaccine SurVaxM to temozolomide improves disease control in patients with progressing metastatic neuroendocrine tumors or neuroendocrine carcinomas, while characterizing the safety and tolerability of the combination. The primary efficacy focus is 6-month progression-free survival, with additional assessment of radiographic response, survival, immune response, MGMT status, and tumor growth kinetics.
Patients: Adults with measurable, pathologically confirmed metastatic and progressing neuroendocrine tumors of gastrointestinal, pancreatic, or thoracic origin with Ki-67 greater than 20%, including well-differentiated grade 3 NETs, or neuroendocrine carcinoma of any origin except small cell lung cancer. Eligible patients must have radiographic progression within the prior 12 months, prior failure of at least one systemic therapy, ECOG performance status 0–1 or Karnofsky performance status at least 80, adequate marrow, hepatic, and renal function, and tumor tissue positive for survivin by immunohistochemistry. Prior temozolomide is not allowed if the patient progressed on it in the advanced-disease setting, and patients with prior SurVaxM, recent checkpoint inhibitor therapy, active autoimmune disease, significant uncontrolled illness, pregnancy, or high-dose systemic corticosteroid use are excluded.
Design: This is an open-label, single-arm phase IIa treatment study. All enrolled patients receive temozolomide plus SurVaxM; there is no randomization or concurrent control arm, although the study is framed around assessing the added value and safety of the combination relative to historical experience with temozolomide. Patients may continue treatment for up to 1 year in the absence of progression or unacceptable toxicity, with possible continuation of temozolomide at investigator discretion.
Treatments: Temozolomide is given orally once daily on days 1–5 of each 28-day cycle for up to 1 year, provided there is no disease progression or unacceptable toxicity. Temozolomide is an alkylating agent that damages tumor-cell DNA and is an established systemic option used in selected patients with advanced neuroendocrine neoplasms, particularly pancreatic NETs and higher-grade well-differentiated disease. SurVaxM, also known as SVN53-67/M57-KLH, is given subcutaneously with Montanide ISA-51 and sargramostim every 2 weeks for 4 priming doses; patients deriving clinical benefit without progression or unacceptable toxicity may receive additional doses at weeks 24, 36, and 48. SurVaxM is an investigational peptide vaccine targeting survivin, an inhibitor-of-apoptosis protein overexpressed in multiple cancers and associated with adverse prognosis; the vaccine is designed to generate survivin-specific cellular and humoral immune responses against survivin-expressing tumor cells. In prior early-phase glioblastoma studies, SurVaxM was immunogenic and generally well tolerated, with mostly low-grade injection-site reactions and encouraging single-arm survival signals when combined with standard temozolomide-based therapy, but randomized efficacy data are not yet established.
Outcomes: The primary outcomes are progression-free survival at 6 months and incidence of adverse events graded by NCI CTCAE v5.0 through up to 1 year. Secondary outcomes include RECIST v1.1 response and clinical benefit rates at 3, 6, 9, and 12 months; overall survival; time to progression; and anti-survivin IgG titer response, defined as titers greater than 30,000. Exploratory analyses include peripheral blood immune markers associated with response, MGMT status correlated with outcome, and radiographic tumor growth rate before and during treatment.
Burden on patient: The expected patient burden is moderate. Temozolomide is oral and administered on a short 5-day schedule each 28-day cycle, which limits infusion-chair time, but the vaccine component requires repeated clinic visits for subcutaneous injections every 2 weeks during the priming phase and additional booster visits at approximately 6, 9, and 12 months for patients benefiting from therapy. Patients also undergo serial blood collections for safety and immune correlative testing, as well as CT or MRI scans for disease assessment; these procedures are generally consistent with oncology trial monitoring and do not appear to include mandatory fresh tumor biopsies or intensive pharmacokinetic sampling. Overall, the main added burden beyond standard temozolomide-based care is the vaccine visit schedule and immune-monitoring blood draws.
Last updated: May 2026
Inclusion Criteria:
* Age ≥ 18 years of age
* Have a Karnofsky performance status ≥ 80 or Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1 (i.e. the patient must be able to care for himself/ herself with occasional help from others)
* Measurable, pathologically confirmed diagnosis of neuroendocrine tumor of gastrointestinal, pancreatic, or thoracic origin with ki67\>20% (well-differentiated G3 NETs) or neuroendocrine carcinoma of any origin excluding small cell lung carcinoma
* Patients must have documented radiographic progression, determined as clinically significant by the treating provider, within the last twelve months on two CT or MRI scans performed at least four weeks apart per RECIST v1.1 criteria. In the case of retreatment, progression may be defined by the treating provider (e.g., clinical, radiographic, biochemical)
* Patients must have failed at least one prior systemic therapy
* Patients who have been on somatostatin analogues (SSA) may continue to take SSA while on study treatment
* Archival neuroendocrine tumor tissue must test positive for survivin presence by clinical immunohistochemistry prior to study enrollment
* Absolute neutrophil count (ANC) ≥ 1.5 x 10\^9/L (obtained within 14 days prior to enrollment)
* Platelets ≥ 100 x 10\^9/L (obtained within 14 days prior to enrollment)
* Hemoglobin (Hgb) \> 9g/dL (obtained within 14 days prior to enrollment)
* Plasma total bilirubin: ≤ 1.5 x upper limit of normal (ULN) (obtained within 14 days prior to enrollment)
* Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 4 x ULN (obtained within 14 days prior to enrollment)
* Creatinine clearance ≥ 60 mL/min (per Cockroft-Gault equation) (obtained within 14 days prior to enrollment)
* Patients on full-dose anticoagulants (e.g., warfarin or low molecular weight \[LMW\] heparin) must meet the following criteria:
* No active bleeding or pathological condition that carries a high risk of bleeding (e.g., tumor involving major vessels or known varices, which carries a significant risk of bleeding in investigator's opinion)
* Participants of child-bearing potential must agree to use adequate contraceptive methods (e.g., hormonal or barrier method of birth control; abstinence) prior to study entry. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately
* Participant must understand the investigational nature of this study and sign an independent ethics committee/institutional review board approved written informed consent form prior to receiving any study related procedure
Exclusion Criteria:
* Patients who have received temozolomide in the advanced disease setting either alone or as part of a combination therapy will be excluded if they progressed while on it
* Has received prior treatment with SurVaxM
* Received an investigational agent within 30 days prior to enrollment
* Participants who have received checkpoint inhibitors within 3 months prior to study enrollment or, those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
* Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, bradycardia, tachycardia or psychiatric illness/social situations that would limit compliance with study requirements and, which in the treating physicians' opinion would jeopardize the ability of the patient to receive the treatment outlined in this protocol with reasonable safety
* Patients with a concurrent or prior malignancy are ineligible unless they are patients with curatively treated carcinoma-in-situ or basal cell carcinoma of the skin. Patients who have been free of disease (any prior malignancy) for at least 3 years are eligible for this study
* Known history of an autoimmune disorder
* Known human immunodeficiency virus (HIV) positivity or acquired immunodeficiency syndrome (AIDS) related illness or other serious medical illness
* Systemic corticosteroid therapy \> 2mg of dexamethasone or equivalent per day at study entry
* Pregnant or nursing female participants
* Unwilling or unable to follow protocol requirements
* Any condition which in the Investigator's opinion deems the participant an unsuitable candidate to receive study drug
* Patients with Hepatitis B or Hepatitis C may be included if there are adequately controlled viral titers and no drug-drug interactions, testing not required
Buffalo, New York, 14263, United States
[email protected] / 716-845-1300
Status: Recruiting