NeuVax (nelipepimut-S) / Dr. Reddy’s, SELLAS Life Sciences - LARVOL DELTA

VADIS: Nelipepimut-S Plus GM-CSF Vaccine Therapy in Treating Patients With Breast Cancer (clinicaltrials.gov) - P2 | N=43 | Completed | Sponsor: National Cancer Institute (NCI) | Active, not recruiting ➔ Completed | Trial completion date: Mar 2024 ➔ May 2023

Trial completion • Trial completion date • Breast Cancer • Oncology • Solid Tumor

Phase II Trial of Nelipepimut-S Peptide Vaccine in Women with Ductal Carcinoma In Situ. (PubMed, Cancer Prev Res (Phila)) - "This trial showed that vaccination of patients with HLA-A2-positive DCIS with NeuVax in the preoperative setting can induce a sustained antigen-specific T-cell response. This provides proof of principle that vaccination in the preoperative or adjuvant setting may stimulate an adaptive immune response that could potentially prevent disease recurrence."

Journal • P2 data • Oncology • CSF2 • HER-2

Super silyl-based stable protecting groups for both the C- and N-terminals of peptides: applied as effective hydrophobic tags in liquid-phase peptide synthesis. (PubMed, Chem Sci) - "The preparation of these tags requires less steps than previously reported tags. Nelipepimut-S was synthesized successfully with different strategies using these two types of super silyl tags."

Journal

Interaction between Radiation Therapy and Targeted Therapies in HER2-Positive Breast Cancer: Literature Review, Levels of Evidence for Safety and Recommendations for Optimal Treatment Sequence. (PubMed, Cancers (Basel)) - " Research was carried out on the following databases: PubMed, EMBASE, ClinicalTrial.gov, Medline, and Web of Science for the terms "radiotherapy", "radiation therapy", "radiosurgery", "local ablative therapy", and "stereotactic", combined with "trastuzumab", "pertuzumab", "trastuzumab emtansine", "TDM-1", "T-Dxd", "trastuzumab deruxtecan", "tucatinib", "lapatinib", "immune checkpoint inhibitors", "atezolizumab", "pembrolizumab", "nivolumab", "E75 vaccine", "interferon", "anti-IL-2", "anti-IL 12", and "ADC". HER2-targeting monoclonal antibodies and checkpoint inhibitors can be combined with radiation, apparently with no excess toxicities. Caution is required when associating radiation with TKI and antibody drugs, considering the limited evidence."

Journal • Review • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Immune Modulation • Oncology • Solid Tumor • HER-2 • IL12A • IL2

VADIS: Nelipepimut-S Plus GM-CSF Vaccine Therapy in Treating Patients With Breast Cancer (clinicaltrials.gov) - P2 | N=43 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | N=13 ➔ 43

Enrollment change • Breast Cancer • Oncology • Solid Tumor • HER-2

Phase II Trial of Nelipepimut-S Peptide Vaccine in Women with Ductal Carcinoma in Situ. (PubMed, Cancer Prev Res (Phila)) - "NPS+GM-CSF is safe and well-tolerated when given preoperatively to DCIS patients. In HLA-A2-positive DCIS patients, two inoculations with NPS+GM-CSF can induce in vivo immunity and a continued antigen-specific T-cell response one-month post-surgery."

Journal • P2 data • Oncology • CSF2 • HER-2

Phase II Trial of Nelipepimut-S Peptide Vaccine in Women with Ductal Carcinoma In Situ. (PubMed, Cancer Prev Res (Phila)) - "This trial showed that vaccination of patients with HLA-A2-positive DCIS with NeuVax in the preoperative setting can induce a sustained antigen-specific T-cell response. This provides proof of principle that vaccination in the preoperative or adjuvant setting may stimulate an adaptive immune response that could potentially prevent disease recurrence."

Journal • P2 data • Oncology

Results of a phase 2 trial of combination immunotherapy with concurrent Nelipepimut-S + GM-CSF and Trastuzumab in high-risk HER2+ breast cancer patients (SABCS 2022) - "Combination immunotherapy with concurrent nelipepimut-S + GM- CSF and trastuzumab is safe, however there was no difference in iDFS or DRFS among high- risk HER2+ breast cancer patients who received nelipepimut-S + GM-CSF compared to GM- CSF alone. We observed a trend towards improved iDFS in patients with a positive DTH response to nelipepimut-S, though it was not statistically significant."

Clinical • P2 data • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • CSF2 • HER-2

Final analysis of Nelipepimut-S plus GM-CSF with trastuzumab versus trastuzumab alone to prevent recurrences in high-risk, HER2 low-expressing breast cancer: A prospective, randomized, blinded, multicenter phase IIb trial. (ASCO-SITC 2019) - P2; "The combination of NPS with Tz is safe with no added toxicity compared to Tz alone, even after prolonged exposure (25.7 mo). In this final analysis, there was a trend towards benefit in the ITT population that improved since the interim analysis with added f/u. The significant benefit seen at interim in the TNBC pts continued to strengthen in the VG group."

Clinical • P2b data

Pre-specified interim analysis in a prospective, randomized phase II trial of trastuzumab vs trastuzumab + NeuVax to prevent breast cancer recurrence in HER2+ breast cancer patients (AACR 2017) - "The combination of Tz and Neuvax in HER2+ BCa pts is well tolerated and the cardiac effects from Tz are not worsened by the addition of NeuVax. We will continue to enroll up to our goal of 100 pts in this ongoing trial, and will report immunologic and clinical outcomes in the planned primary analysis after 24-months follow-up."

Clinical • P2 data • P2/3 data • P3 data • Biosimilar • Breast Cancer • HER2 Breast Cancer • Hormone Receptor Breast Cancer • Oncology

"Bir de Neuvax var, onu hiç bir pipeline'da bulamıyorum, sonlandırıldı mı denemeleri?" (@ilhanzeynepka)

Phase II Trial of Combination Immunotherapy With NeuVax and Trastuzumab in High-risk HER2+ Breast Cancer Patients (clinicaltrials.gov) - P2 | N=100 | Completed | Sponsor: Cancer Insight, LLC | Active, not recruiting ➔ Completed

Trial completion • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Final analysis of Nelipepimut-S plus GM-CSF with trastuzumab versus trastuzumab alone to prevent recurrences in high-risk, HER2 low-expressing breast cancer: A prospective, randomized, blinded, multicenter phase IIb trial. (ASCO-SITC 2019) - P2; "The combination of NPS with Tz is safe with no added toxicity compared to Tz alone, even after prolonged exposure (25.7 mo). In this final analysis, there was a trend towards benefit in the ITT population that improved since the interim analysis with added f/u. The significant benefit seen at interim in the TNBC pts continued to strengthen in the VG group."

Clinical • P2b data

Subgroups analysis of a multicenter, prospective, randomized, blinded phase 2b trial of trastuzumab + nelipeptimut-S (NeuVax) vs trastuzumab for prevention of recurrence in breast cancer patients (SABCS 2018) - "Examining the subgroups from the pre-specified interim analysis demonstrates a highly significant clinical benefit in TNBC pts overall. Within the TNBC cohort, specific benefit was seen in pts who received chemotherapy neoadjuvantly, expressed lower HER2, were earlier stage, and were older in age. These factors may help enrich the TNBC population targeted in a definitive Phase 3 study in TNBC patients with residual disease after neoadjuvant chemotherapy. "

Clinical • P2b data • Breast Cancer • HER2 Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer

Correlation between response and HLA type in a randomized phase IIb trial of NeuVax + trastuzumab in HER2 low-expressing breast cancer patients to prevent recurrence (SITC 2018) - P2; "Conclusions HLA-A24+ TNBC patients had a significant improvement in DFS despite the lowest predicted binding potential between E75 and this HLA-type. This suggests that lower-affinity peptides may generate a favorable immunologic response possibly due to decreased exposure and tolerance to epitopes."

Clinical • IO biomarker • P2b data • HER2 Breast Cancer • Triple Negative Breast Cancer

Pre-specified interim analysis of a randomized phase 2b trial of trastuzumab + nelipeptimut-S (NeuVax) vs trastuzumab for the prevention of recurrence demonstrates benefit in triple negative (HER2 low-expressing) breast cancer patients (ESMO 2018) - P2; "NeuVax + Tz is safe without added cardiac toxicity compared to Tz alone. The pre-specified IA shows efficacy trends overall in favor of the NeuVax + Tz combination, but most importantly demonstrates a highly significant clinical benefit in TNBC pts, suggesting the need for a definitive Ph3 study in this underserved pt population."

Clinical • P2b data • HER2 Breast Cancer • Hormone Receptor Breast Cancer • Triple Negative Breast Cancer

Final analysis of Nelipepimut-S plus GM-CSF with trastuzumab versus trastuzumab alone to prevent recurrences in high-risk, HER2 low-expressing breast cancer: A prospective, randomized, blinded, multicenter phase IIb trial. (ASCO-SITC 2019) - P2; "The combination of NPS with Tz is safe with no added toxicity compared to Tz alone, even after prolonged exposure (25.7 mo). In this final analysis, there was a trend towards benefit in the ITT population that improved since the interim analysis with added f/u. The significant benefit seen at interim in the TNBC pts continued to strengthen in the VG group."

Clinical • P2b data • Breast Cancer • HER2 Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer

[VIRTUAL] Vadis trial: phase II trial of Nelipepimut-S peptide vaccine in women with DCIS of the breast (SABCS 2020) - "NPS+GM-CSF is safe and well-tolerated when given preoperatively to patients with DCIS. In HLA-A2 positive patients with DCIS, a single inoculation with NPS+GM-CSF can induce in vivo immunity and a continued antigen-specific T-cell response one month post-surgery. This data provides support for further testing of NPS+GM-CSF in the neoadjuvant and adjuvant settings in an attempt to prevent invasive recurrence in DCIS."

Clinical • P2 data • Breast Cancer • Oncology • CSF2 • HER-2

Immunologic responses in triple-negative breast cancer patients in a randomized phase IIb trial of nelipepimut-S plus trastuzumab versus trastuzumab alone to prevent recurrence. (ASCO 2019) - P2; "NPS+Tz combination is more efficacious in generating time-dependent antigen (NPS)-specific CTL by both ex vivo and in vivo measures vs Tz. Based on these preliminary data, it appears that both ex vivo and in vivo IR to NPS were attenuated in pts with TNBC recurrence. Further analysis of read-outs from these assays to validate the relationship of IRs to clinical effect seen with NPS+Tz in TNBC pts is underway."

Clinical • P2b data • Breast Cancer • HER2 Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer

Application of HER2 peptide vaccines in patients with breast cancer: a systematic review and meta-analysis. (PubMed, Cancer Cell Int) - "The E75 vaccine was effective and safe in patients with breast cancer. The GP2 vaccine could elicit a strong immune response, but more trials are needed to confirm its clinical efficacy."

Journal • Retrospective data • Review • Breast Cancer • HER2 Breast Cancer • Immunology • Oncology • Solid Tumor • HER-2

Novel Vaccine Combos Represent a Promising Treatment Approach in Breast Cancer (OncLive) - "The future of therapeutic vaccines in breast cancer will be dependent on their use in combination with standard anticancer drugs, checkpoint antagonists, and distinct checkpoint inhibitors, Leisha A. Emens, MD, PhD, said in a presentation during the 20th Annual International Congress on the Future of Breast Cancer East. Vaccine trials have historically not had much success in breast cancer, and research had been slowed by the advent of checkpoint inhibitors, said Emens...during the meeting, which was hosted by the Physicians' Education Resource (PER), LLC."

Media quote

SELLAS Life Sciences Reports First Quarter 2021 Financial Results and Provides Business Update (GlobeNewswire) - "Pipeline Updates: (i) Galinpepimut-S (GPS): The Company expects to activate sites...for the Phase 3 REGAL study in patients with AML...and begin enrolling patients in France, Germany and Greece by the end of the second quarter of 2021; (ii) Nelipepimut-S (NPS): The Company expects the primary analysis in...the ongoing investigator sponsored study of NPS plus trastuzumab in high risk HER2 3+ breast cancer patients...to be completed by the end of 2021."

P2 data • Trial status • Acute Myelogenous Leukemia • Breast Cancer • Hematological Malignancies • HER2 Positive Breast Cancer • Oncology

Immunotherapy for the Breast Cancer treatment: Current Evidence and Therapeutic Options. (PubMed, Endocr Metab Immune Disord Drug Targets) - "Although, commonly used treatments like trastuzumab/pertuzumab for human epidermal growth factor receptor 2 (Her2) positive and hormone therapy for estrogen receptor (ER) positive and/or progesterone receptor (PR) positive BC are specific but triple negative breast cancer (TNBC) cases remain a great challenge for treatment measures. Immune checkpoint inhibitors (anti-PD-1/ anti-CTLA-4) and anti-cancer vaccines (NeuVax, Muc-1, AVX901, INO-1400 and CEA), either alone or in combination with other therapies have created new paradigm in therapeutic world. In this review, we highlighted the current immunotherapeutic aspects and their ongoing trials towards the better treatment regimen for BC."

Journal • Breast Cancer • HER2 Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Immune Modulation • Immunology • Inflammation • Oncology • Solid Tumor • Triple Negative Breast Cancer • ER • HER-2 • MUC1 • PGR

Phase II Trial of Combination Immunotherapy With NeuVax and Trastuzumab in High-risk HER2+ Breast Cancer Patients (clinicaltrials.gov) - P2; N=100; Active, not recruiting; Sponsor: Cancer Insight, LLC; Trial completion date: Mar 2021 ➔ Dec 2021; Trial primary completion date: Mar 2021 ➔ Dec 2021

Clinical • Trial completion date • Trial primary completion date • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Results of a randomized phase IIb trial of nelipepimut-S + trastuzumab vs trastuzumab to prevent recurrences in high-risk HER2 low-expressing breast cancer patients. (PubMed, Clin Cancer Res) - P2; "The combination of NPS with trastuzumab is safe. In HER2 low-expressing breast cancer, no significant difference in DFS was seen in the intention-to-treat analysis; however, significant clinical benefit was seen in TNBC patients. These findings warrant further investigation in a phase III randomized trial."

Clinical • Journal • P2b data • Breast Cancer • HER2 Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • CSF2 • HER-2