AST-301 / University of Washington, Aston Sci., EpiThany - LARVOL DELTA

Vaccine Therapy With Sargramostim (GM-CSF) in Treating Patients With Her-2 Positive Stage III-IV Breast Cancer or Ovarian Cancer (clinicaltrials.gov) - P1 | N=66 | Completed | Sponsor: University of Washington | Active, not recruiting ➔ Completed

Trial completion • Breast Cancer • Germ Cell Tumors • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Ovarian Cancer • Solid Tumor • HER-2 • MUC16

Vaccine Therapy With Sargramostim (GM-CSF) in Treating Patients With Her-2 Positive Stage III-IV Breast Cancer or Ovarian Cancer (clinicaltrials.gov) - P1 | N=66 | Active, not recruiting | Sponsor: University of Washington | Trial completion date: Dec 2024 ➔ Apr 2025

Trial completion date • Breast Cancer • Germ Cell Tumors • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Ovarian Cancer • Solid Tumor • HER-2 • MUC16

Humor Me With Calcium: A Rare Presentation of Humoral Hypercalcemia of Malignancy Secondary to Cholangiocarcinoma (ACG 2024) - "Labs were notable for a corrected calcium of 15.8mg/dL, alkaline phosphatase of 442 U/L, AST 301 U/L, ALT 13 U/L, phosphorus 1.6mg/dL, parathyroid hormone of less than 6.0pg/mL and 25-hydroxyvitamin D of 7.0ng/dL. The hypercalcemia improved with fluids and pamidronate...There is also pericholecystic fluid noted, likely related to ascites. There is no visible evidence of biliary ductal dilatation in either view."

Biliary Cancer • Breast Cancer • Cardiovascular • Cholangiocarcinoma • Coronary Artery Disease • Endocrine Disorders • Endometrial Cancer • Gastrointestinal Cancer • Gastrointestinal Disorder • Hematological Malignancies • Hepatocellular Cancer • Hepatology • Lymphoma • Metabolic Disorders • Nicotine Addiction • Oncology • Ovarian Cancer • Renal Cell Carcinoma • Solid Tumor • AFP

Conerstone3: Therapeutic Cancer Vaccine (AST-301, pNGVL3-hICD) in Gastric Cancer (clinicaltrials.gov) - P2 | N=24 | Recruiting | Sponsor: Aston Sci. Inc. | Trial primary completion date: Oct 2023 ➔ Oct 2025

Trial primary completion date • Gastric Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • HER-2

Cornerstone001: Therapeutic Cancer Vaccine (AST-301, pNGVL3-hICD) in Patients With Breast Cancer (clinicaltrials.gov) - P2 | N=10 | Terminated | Sponsor: Aston Sci. Inc. | N=146 ➔ 10 | Trial completion date: Dec 2025 ➔ May 2024 | Recruiting ➔ Terminated | Trial primary completion date: Aug 2025 ➔ May 2024; Difficulty in recruiting patients

Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • HER-2

AST-301,a pDNA-based cancer vaccine encoding HER2-ICD, enhances anti-tumor effect of HER2-ADC in a HER2-expressed gastric cancer xenograft model (AACR 2024) - "Enhertu (1 or 3 mg/kg, intravenous injection) was administered to twice for four weeks. With combining AST-301 and HER2 ADCs, it was demonstrated that anti-tumor effect was likely synergistic in the athymic mouse model. Phase 2 study of AST-301 in HER2-expressed gastric cancer has been on going (CornerStone-003, NCT 05771584)."

Preclinical • Breast Cancer • Gastric Cancer • Gastrointestinal Cancer • HER2 Breast Cancer • Oncology • Solid Tumor • HER-2

Aston Science attends the American Association for Cancer Research… Announcement of results from a total of 6 studies, including cancer treatment vaccine [Google translation] (MedigateNews) - "Additionally, Aston Science presented at this academic conference: immunogenicity preclinical results of AST-11X, a vaccine using KRAS non-mutated class II epitope; AST-301 (HER2 vaccine, clinical trial in gastric cancer) Preclinical results of antitumor effect for combination therapy with HER2 ADC (Phase 2 drug); Preclinical results for antitumor effect for combination therapy with AST-201 (IGFBP2 vaccine, phase 2 clinical drug) and Keytruda in ovarian cancer; Advanced solid cancer A total of six preclinical results, including the preclinical results of AST-05X, a targeted treatment targeting ISR (integrated stress response) inhibition, are scheduled to be disclosed through poster presentations."

Preclinical • Gastric Cancer • Gastrointestinal Cancer • Gynecologic Cancers • Oncology • Ovarian Cancer • Solid Tumor

AST-301, a pDNA-based cancer vaccine encoding HER2-ICD, enhances anti-tumor effect of HER2-ADC in a HER2-expressed gastric cancer xenograft model (SITC 2023) - "Results It was showed that adding AST-301 to LCB01 or Kadcyla inhibited a tumor growth based on TGI rate at days 25; AST-301 combining with LCB01 vs LCB01 mono (52% vs 43%), AST-301 combining with Kadcyla vs Kadcyla mono (43% vs 34%). Immunologically, the combination of AST-301 and HER2 ADCs suppressed the increase of MDSC in the tumor environment. Based on those supporting data, phase 2 study of AST-301 in HER2-expressed gastric cancer has been active (CornerStone-003, NCT#05771584)."

Preclinical • Breast Cancer • Gastric Cancer • Gastrointestinal Cancer • HER2 Breast Cancer • Oncology • Solid Tumor • HER-2

Antitumor effect of HER2-hICD vaccine combining with HER2 ADC depending on T cell existence in a mouse model: pooled analysis (SITC 2023) - P1 | "Conclusions Given that clear antitumor effect of AST-301-based regimen was observed in CD34+ humanized mouse model than athymic BALB/c nude mouse model, it is proven that the presence of T cells is very crucial in pharmacological efficacy of cancer vaccine approach and relevant in-vivo efficacy study. These translational researches are supporting a clinical study of AST-301 combining with HER2-ADCs."

Preclinical • Retrospective data • Breast Cancer • Gastric Cancer • Gastrointestinal Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • CD34 • HER-2

PSC in an Acutely Psychotic Patient (ACG 2023) - "He was found to have elevated liver enzymes—AST 301, ALT 327, Alk phos 862, GGT 1677, total bilirubin 0.8, INR 1.3, ammonia 169—without asterixis or stigmata of chronic liver disease on exam...He was given antipsychotics, a dextrose infusion and low protein diet for suspected urea cycle disorder, and lactulose and rifaximin for hepatic encephalopathy...He was started on ursodiol and underwent colonoscopy without evidence of IBD...Ultimately, MRCP was needed to solidify the diagnosis. While an uncommon manifestation of hepatic encephalopathy, psychosis in this case led to the discovery of PSC."

Clinical • Bipolar Disorder • Cholestasis • CNS Disorders • Dermatology • Fatigue • Fibrosis • Gastroenterology • Gastrointestinal Disorder • Hepatic Encephalopathy • Hepatology • Immunology • Inflammation • Inflammatory Bowel Disease • Mental Retardation • Metabolic Disorders • Pruritus • Psychiatry • ALK

Conerstone3: Therapeutic Cancer Vaccine (AST-301, pNGVL3-hICD) in Gastric Cancer (clinicaltrials.gov) - P2 | N=24 | Recruiting | Sponsor: Aston Sci. Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Gastric Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • CD4 • CD8 • HER-2

Aston Science announces preclinical results of two cancer treatment vaccines at AACR in the US [Google translation] (HIT News) - "Aston Science...announced on the 20th that it announced the results of preclinical studies of two cancer treatment vaccines at the American Association for Cancer Research (AACR 2023) held in Orlando, USA from the 14th to the 19th....Through its first poster on the 16th, the company announced the synergistic effect of the combined administration of 'AST-301 (development code name)' and Keytruda using a humanized gastric cancer mouse model....According to this announcement, in a humanized mouse gastric cancer model transplanted with human CD34+ blood stem cells, the standard-dose combination treatment group of AST-301 and Keytruda showed superior tumor suppression effect compared to the standard-dose Keytruda alone treatment group."

Preclinical • Gastric Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

AST-301, a pDNA-based therapeutic cancer vaccine encoding HER2 ICD, improves the efficacy of checkpoint blockade therapy in CD34+ humanized gastric cancer mouse model (AACR 2023) - P1 | "To confirm the tumor suppressive effect of pembrolizumab (anti-PD-1) treatment combined with AST-301 in the hu-CD34+ hematopoietic stem cell-engrafted NSG mice that formed tumors with NCI-N87, AST-301 (100 μg) and pembrolizumab (5 mg/kg) were administered into mice once a week for a total of 3 times and one booster doses of AST-301 was injected at week 4. Currently, we are ongoing study to prove the anti-tumor synergistic effects of the combination of AST-301 and various FDA-approved Antibody Drug Conjugates (ADCs). This effort is focused on narrowing the administration doses to low levels to resolve the safety issue of ADC or ICI, and it will strongly support the diverse applicability of the cancer therapeutic vaccine."

Checkpoint block • Checkpoint inhibition • Preclinical • Gastric Cancer • Gastrointestinal Cancer • Oncology • Ovarian Cancer • Solid Tumor • CD34 • CD8 • HER-2 • PD-L1

Vaccine Therapy With or Without Polysaccharide-K in Patients With Stage IV HER2 Positive Breast Cancer Receiving HER2-Targeted Monoclonal Antibody Therapy (clinicaltrials.gov) - P1/2 | N=31 | Completed | Sponsor: University of Washington | Unknown status ➔ Completed

IO biomarker • Metastases • Trial completion • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2 • IFNG • LAMP1 • NCAM1

The anti-tumor activity of HER-2/neu ICD therapeutic cancer vaccine (AST-301, pNGVL3-hICD) in Her2-expressed gastric cancer xenograft model (SITC 2021) - P1 | "Treatment groups were assigned as AST-301 alone (AST-301, 0.1 mg/head, i.d.), Trastuzumab (TZM, 20 mg/kg, i.p.) or AST-301 combining with Trastuzumab (AST-301+TZM) respectively. Conclusions Tumor protective and tumor therapeutic effect of AST-301 were demonstrated well in various doses and regimens on HER2/neu positive gastric cancer xenograft model. These data would be supporting a proof of concept (PoC) clinical study of HER-2/neu ICD therapeutic cancer vaccine in certain type of HER2/neu-expressed gastric cancer patient."

Preclinical • Breast Cancer • Gastric Cancer • Gastrointestinal Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Aston Science announces preclinical trial of cancer vaccine and Keytruda combination at AACR (Hankyung) - "Aston Science announced on the 9th that it will present the results of a preclinical study on the combination of 'AST-301', a HER2-ICD cancer vaccine, and Keytruda at the American Association for Cancer Research (AACR) to be held on the 14th of next month....At this AACR, Aston Science will also present the results of a preclinical study of 'AST-021p', a cancer vaccine using a peptide-based HSP90 antigenic determinant (epitope). This vaccine is currently undergoing phase 1 (CornerStone-002) for patients with solid cancer. The final results of the second half of the year are about to be announced."

P1 data • Preclinical • Gastric Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

80% of Patients in Investigational Breast Cancer Vaccine Trial Alive after 10 Years (BioSpace) - P1 | N=66 | NCT00436254 | "Researchers from the University of Washington School of Medicine have developed an investigational vaccine that can safely elicit an immune response against the HER2 protein, a key marker in breast cancer....In the 66 inoculated patients, the majority of vaccine-related toxicities were mild, classified as either grade 1 or 2 in the third version of the Common Terminology Criteria for Adverse Events....Those who had been inoculated with the 100-µg and 500-µg demonstrated significantly stronger type 1 immune response against the HER2 intracellular domain at most of the assessment time points, compared with the 10-µg shot. After controlling for baseline factors, the difference in response had p-values of 0.003 and lower than 0.001, respectively....UW Medicine researchers have already initiated a larger Phase II trial, pitting their investigational vaccine against an active comparator. Enrollment for this study is ongoing and has more than 100 participants."

P1 data • Trial status • Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor

Aston Sci grabs FDA nod for phase 2 clinical trials of its therapeutic cancer vaccine (Korea Biomedical Review) - "Aston Science said on Wednesday that it obtained approval from the U.S. Food and Drug Administration for phase 2 clinical trials of its therapeutic cancer vaccine AST-301 on patients with triple-negative breast cancer (TNBC)....The phase 2 clinical trial administers combinations with Xeloda or Keytruda, a standard treatment, in patients with a high risk of recurrence after HER2 low-expression breast cancer surgery....Furthermore, the phase 2 clinical trial applies the same patient group and design used in phase 3 clinical trials. Depending on the interim results, it will enable discussion of expedited authorization of biological license application (BLA) or pivotal cohort expansion to generate corroborative clinical data in phase 2 clinical trials, the company said."

IND • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer

Cornerstone001: Therapeutic Cancer Vaccine (AST-301, pNGVL3-hICD) in Patients With Breast Cancer (clinicaltrials.gov) - P2 | N=146 | Recruiting | Sponsor: Aston Sci. Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • HER-2 • IFNG

Aston Sci. Announces the Study Results of Two Therapeutic Cancer Vaccines at the 2021 Society for Immunotherapy of Cancer (SITC) Annual Meeting (Businesswire) - "The data from the study of AST-301, a pDNA-based cancer vaccine, using mice models with HER2-expressing gastric cancer shows the efficacy of monotherapy and combination therapy of the vaccine....Aston Sci. also presents the efficacy of combination therapy of AST-021p using a breast cancer mouse model....The results of comparative evaluation on tumor growth inhibition and immunogenicity when used in combination with several immune adjuvants, including “L-pampo™” (TLR-2/3 ligand-based immune adjuvant) in-licensed from the CHA Vaccine Institute, will be presented."

Preclinical • Gastric Cancer • Gastrointestinal Cancer • Oncology

Vaccine Therapy With Sargramostim (GM-CSF) in Treating Patients With Her-2 Positive Stage III-IV Breast Cancer or Ovarian Cancer (clinicaltrials.gov) - P1; N=66; Active, not recruiting; Sponsor: University of Washington; Trial completion date: Dec 2023 ➔ Dec 2024

Clinical • Trial completion date • Breast Cancer • Germ Cell Tumors • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Ovarian Cancer • Solid Tumor • HER-2 • MUC16

VADIS: Nelipepimut-S Plus GM-CSF Vaccine Therapy in Treating Patients With Breast Cancer (clinicaltrials.gov) - P2; N=108; Recruiting; Sponsor: National Cancer Institute (NCI); Suspended ➔ Recruiting

Enrollment open • Biosimilar • Breast Cancer • Oncology

Vaccine Therapy in Treating Patients With Previously Treated Stage II-III HER2-Positive Breast Cancer (clinicaltrials.gov) - P1; N=24; Active, not recruiting; Sponsor: Mayo Clinic; Recruiting -> Active, not recruiting

Enrollment closed • Biosimilar • Breast Cancer • Oncology • Triple Negative Breast Cancer

Phase I/II study of adoptive T cell therapy following in vivo priming with a HER2 peptide-based vaccine in patients with stage IV breast cancer (SABCS 2011) - P1/2, N=20; The aim of the study is to evaluate the safety of infusing escalating doses of HER2 specific T cells into pts with advanced HER2+ BC using ex vivo expanded autologous T cells, to investigate to what extent HER2 specific T cell immunity can be boosted or generated in individuals after infusion of HER2 specific T cells, to evaluate how long T cell immune augmentation persists in vivo after adoptive transfer of HER2 specific T cells and subsequent booster immunizations

P1/2 trial design • Breast Cancer • Oncology