UV1 Cancer Vaccine Clinical Trials, Efficacy, Indication, Side Effects
Ultimovacs ASA's UV1 is a peptide-based vaccine inducing a specific T-cell response against the universal cancer antigen telomerase. As a universal cancer vaccine, UV1's unique action mechanism can apply to most cancer types. Unlike algorithm-selected vaccine peptides, the UV1 peptides contain epitopes documented by cancer patients' immune systems. In addition, the UV1 universal cancer vaccine candidate leverages the high prevalence of the human telomerase (hTERT) to effectively cross the dynamic stages of the tumor's growth and microenvironment.
Immune responses against several hTERT epitopes, including novel hTERT epitopes not present in the vaccines, were detected in blood samples from long-term surviving patients following vaccine treatment but not in patients without clinical benefit. Based on these data, three peptides to elicit robust T cell responses across different cancer types were selected as the UV1 vaccine components.
UV1 is being developed as a therapeutic cancer vaccine, which may serve as a platform for use combined with other immunotherapy that requires an ongoing T cell response for their mode of action. In addition, UV1's unique mechanism of action can apply to most cancer types. UV1 consists of long, synthetic peptides that induce CD4+ T cells displaying a Th1 cytokine profile. By directing the immune system to hTERT antigens in over 80% of all cancers, UV1 drives CD4 helper T cells to the tumor to activate an immune system cascade to increase anti-tumor responses.
On March 2, 2024, Ultimovacs ASA announced that the results from the randomized controlled Phase II clinical trial, NIPU, were published in the European Journal of Cancer. On August 5, 2024, Ultimovacs announced the topline results from the Phase II FOCUS trial (NCT05075122). The topline data readout demonstrated that adding UV1 to the standard of care pembrolizumab did not lead to clinical benefits in progression free survival or overall survival in those late-stage HNSCC patients, therefore, the study did not meet its primary and secondary endpoints. Ultimovacs is also investigating UV1 in ovarian cancer in the ongoing Phase II DOVACC trial, which evaluates a combination of olaparib and durvalumab +/- UV1 vs. olaparib alone as second-line maintenance treatment for patients with high-grade BRCA-negative ovarian cancer. Topline results are expected in the first half of 2025, well within the current financial runway, which reaches the fourth quarter of 2025.
Oslo, Norway-based Ultimovacs ASA is a pharmaceutical company (OSE ULTI) developing novel immunotherapies against cancer. The lead product candidate is UV1, a peptide-based vaccine inducing a specific T cell response against the universal cancer antigen telomerase and immune activation for a prostate cancer-specific therapeutic. The Company's clinical studies are listed here.
UV1 Cancer Vaccine Indication
The UV1 telomerase peptide vaccine has demonstrated robust immune response induction and promising clinical activity in several malignancies. Ultimovacs has a long-standing commitment to the development of UV1-based treatments for melanoma. Malignant melanoma is a skin cancer with a significant and unmet medical need for improved therapies. More than 130,000 new cases of melanoma are diagnosed worldwide every year, and an estimated 50,000 people die from metastatic melanoma every year.
UV1 Cancer Vaccine News
October 17, 2023 - "For patients with malignant mesothelioma, few treatment options are available after first-line chemotherapy. The NIPU study showed that patients receiving UV1 vaccination as an add-on to nivolumab and ipilimumab experienced an increased objective response rate and a clinically meaningful prolonged survival. These encouraging results provide a foundation for advancing further clinical development with UV1 vaccination in mesothelioma patients," said Principal Investigator of the NIPU clinical trial, Professor Åslaug Helland, MD, Ph.D.
October 12, 2023 - Jens Bjørheim, Chief Medical Officer at Ultimovacs, stated in a press release, "The UV1-103 study treats the same patient population as our Phase II study INITIUM. As we await data from the first three randomized UV1 Phase II trials in the near-term, we are increasingly optimistic about UV1's potential to benefit cancer patients."
June 19, 2023 - "We are very encouraged to observe a 67% overall survival rate at 3-year follow-up in this Phase I study, which treats the same patient population as our UV1 Phase II study, INITIUM. These data further strengthen the previously reported results from the study, including good safety for UV1 and a remarkable 33% complete response rate in patients with metastatic malignant melanoma where surgery is not an option. The data continue to show that UV1 in combination with pembrolizumab has promising signs of efficacy," said Jens Bjørheim, Chief Medical Officer at Ultimovacs.
October 25, 2022 - Ultimovacs ASA announced that the first patient had been randomized in the LUNGVAC study. The study in non-small cell lung cancer is the fifth Phase II clinical trial in which UV1 is being investigated in combination with checkpoint inhibitors.
October 18, 2022 - Ultimovacs ASA presented clinical endpoints and biomarker results from patients in the UV1-103 Phase I trial.
June 30, 2022 - Ultimovacs ASA announces the completed recruitment of 154 patients in the INITIUM trial. INITIUM is Ultimovacs' Phase II clinical trial of its universal cancer vaccine UV1 combined with the checkpoint inhibitors ipilimumab and nivolumab in metastatic malignant melanoma. Consistent with INITIUM's event-driven design, topline progression-free survival results will be disclosed after the progression of cancer or death has been observed in 70 patients.
February 17, 2022 - Ultimovacs ASA announced its fourth-quarter 2021 results. A private placement was completed on October 26, 2021, raising gross proceeds of MNOK 270 (net MNOK 259.0).
December 15, 2021 - Ultimovacs ASA announced that the first patient had been enrolled in a randomized Phase II clinical trial (DOVACC) assessing the impact of the UV1 telomerase vaccine on ovarian cancer's standard of maintenance care. Topline data from DOVACC is expected in 2023.
December 2, 2021 - Ultimovacs ASA announced that the U.S. FDA had granted orphan drug designation for the Company's universal cancer vaccine UV1 to treat stage IIB – IV melanoma. UV1 is used as an add-on therapy to checkpoint inhibitors ipilimumab and nivolumab. UV1 is currently being studied as a first-line treatment for metastatic melanoma in a Phase II trial named INITIUM.
November 11, 2021 - Ultimovacs ASA announced its third-quarter 2021 results. Highlights for the third quarter of 2021: Ultimovacs reported that UV1 would be investigated in a Phase II clinical trial in combination with pembrolizumab in non-small cell lung cancer. A private placement was completed on 26 October 2021, raising gross proceeds of MNOK 270. Total cash and cash equivalents were reduced by MNOK32.9 during Q3-21 and amounted to MNOK 347.8 as of 30 September 2021.
November 9, 2021 - The Company announced UV1 vaccine combined with ipilimumab was found in a clinical trial to induce immune responses in 91% of melanoma patients. And the immune responses persist and are detectable for up to 5 years.
October 26, 2021 - Ultimovacs announced that UV1 would be investigated in a Phase II clinical trial with pembrolizumab in non-small cell lung cancer (NSCLC). The LUNGVAC trial will be a multi-center, randomized, open-label trial sponsored by Drammen Hospital, a leading oncology research center in Norway. The trial will enroll approximately 138 patients and be conducted at 8-10 clinical centers in Norway.
October 21, 2021 - Ultimovacs ASA announced its universal cancer vaccine, UV1, combined with checkpoint inhibitors, has received Fast Track designation from the U.S. FDA to treat unresectable or metastatic melanoma as an add-on therapy to pembrolizumab or as an add-on therapy to ipilimumab. Ultimovacs is evaluating UV1 as an add-on therapy to ipilimumab and nivolumab as first-line treatment for unresectable or metastatic melanoma in a Phase II study named INITIUM.
October 13, 2021 - Ultimovacs ASA announced continuing positive topline clinical trial results. The 24-month follow-up data compares favorably with an earlier large-scale study of pembrolizumab alone, which showed an overall survival rate of 58% after 24 months and median progression-free survival of 5.5-11.6 months.
August 20, 2021 - The Company posted the 'Enabling the Immune System to Fight Cancer' presentation - Encouraging results from the Phase I clinical trial of UV1 combined with pembrolizumab in malignant melanoma. And it announced its second-quarter 2021 results.
June 1, 2021 - Ultimovacs announced a peer-reviewed article published in The Journal of Translational Medicine that outlines the mechanistic rationale for combining UV1 with two checkpoint inhibitors, ipilimumab and nivolumab. The dual use of ipilimumab and nivolumab was recently approved as first-line therapy in malignant pleural mesothelioma (MPM), with few therapeutic options available. However, Haakensen et al. explain in the article that observed response rates with checkpoint inhibitors have been moderate in MPM compared to documented performance for the combination of checkpoint inhibitors in other cancers, suggesting that checkpoint inhibitors alone may be insufficient to trigger an immune response.
May 11, 2021 - Ultimovacs ASA announced the publication in Frontiers in Immunology of its positive long-term Overall Survival data from the Phase I trial evaluating the Company's universal cancer vaccine, UV1, in combination with checkpoint inhibitor ipilimumab in patients with metastatic malignant melanoma. As published in the journal, in addition to the achievement of the primary endpoints of safety and tolerability, 50% of the patients were still alive at the data cut-off, supporting the combination of the Company's proprietary UV1 vaccine with ipilimumab, a CTLA-4 checkpoint inhibitor, and standard-of-care treatment, in this late-stage patient population.
December 22, 2020 - Ultimovacs ASA - Initiates FOCUS Phase II Trial for Universal Cancer Vaccine, UV1, Head and Neck Cancer Patients Receiving Pembrolizumab. The FOCUS trial is Ultimovacs' fourth Phase II clinical trial with UV1 and comes in addition to the collaboration Phase II trial announced in May 2020.
February 4, 2020 - Study: Combining UV1 and ipilimumab is safe and induces clinical melanoma responses. The high proportion of immunological responders and early induction of detectable immune responses suggest synergism.
UV1 Cancer Vaccine Clinical Trials
UV1 has been tested in several clinical trials, maintaining a positive safety and tolerability profile and encouraging efficacy signals.
The phase II clinical trial results, NIPU, were published in the European Journal of Cancer. The open-label, multi-center Phase II trial was sponsored by Oslo University Hospital with support from Bristol-Myers Squibb and Ultimovacs. The study did not meet its primary endpoint of improved progression-free survival (PFS) based on blinded independent central review (BICR). Analyses on the secondary endpoints, objective response rate (ORR) by BICR and overall survival (OS), showed a significant benefit of adding the UV1 vaccine to ipilimumab and nivolumab. Local assessment demonstrated an improved PFS among patients in the vaccine arm for all histological subtypes combined, and new subgroup analysis shows further improvement for the epithelioid subtype. The epithelioid subtype represents approximately 70% of all patients with mesothelioma. The safety profile confirms the good safety profile for the UV1 vaccine.
Building on Phase I results, Ultimovacs is enrolling INITIUM, its Phase II clinical trial evaluating UV1 combined with ipilimumab and nivolumab in patients with metastatic malignant melanoma. The Company expects to announce the trial's primary endpoint data in 2H2022. In addition, Ultimovacs has an ongoing and fully-enrolled Phase I trial evaluating UV1 combined with pembrolizumab, a PD-1 checkpoint inhibitor, as a first-line treatment in metastatic malignant melanoma patients. Ultimovacs anticipates announcing data on the primary endpoints for the NIPU and INITIUM studies in 2H2022 and the DOVACC and FOCUS studies in 2023.
Clinical analyses from the UV1-103 study announced on October 18, 2022, indicate efficacy in patients with low levels of PD-L1, a critical predictive biomarker associated with lower efficacy for pembrolizumab and other anti-PD-1 therapies in some tumor types. In addition, the analyses showed robust responses in patients treated with the combination of UV1 and pembrolizumab, regardless of patients' PD-L1 status. In addition to the sub-analysis of the PD-L1 status, the study also evaluated four other key predictive biomarkers, including baseline tumor mutational burden (TMB), predicted neoantigens, interferon-gamma (IFN-gamma) gene signature, and levels of tumor-infiltrating lymphocytes. The analyses of these five biomarkers signal efficacy in patients treated with UV1 in combination with pembrolizumab, regardless of the tumor phenotype.
On October 12, 2023, Ultimovacs announced encouraging overall survival data from cohort 1 in the UV1-103 Phase I clinical trial in malignant melanoma. No further deaths have been reported among the patients in cohort 1 who were alive at the 3-year follow-up, reaffirming an encouraging trend of durable overall survival benefit from UV1 vaccination. Ultimovacs has previously reported data showing a complete response rate in the UV1-103 study of 33% (complete disappearance of tumors) and an objective response rate of 57% (full or partial disappearance of tumors). On October 17, 2023, the first demonstration of universal cancer vaccine efficacy and therapeutic impact in a randomized Phase II clinical trial supported further clinical development. The UV1 cancer vaccination combined with ipilimumab and nivolumab reduced the risk of death by 27%, meeting the protocol predefined threshold for statistical significance in a hard-to-treat patient group with currently no standard-of-care treatment options.
Ultimovacs ASA - positive topline results from the first cohort of 20 patients in its ongoing US-based Phase I clinical trial evaluating the Company's lead candidate, UV1, combined with a PD-1 checkpoint inhibitor, pembrolizumab, as a first-line treatment in patients with metastatic malignant melanoma. The results confirm the achievement of the primary safety and tolerability endpoints and indicate initial signs of clinical response.
UV1 is being tested in different randomized Phase II trials: The INITIUM trial is an Ultimovacs-sponsored, global, randomized Phase II trial for patients with metastatic malignant melanoma; The NIPU trial is a randomized, multi-center Phase II trial in which the universal cancer vaccine, UV1, is investigated in combination with the checkpoint inhibitors, ipilimumab, and nivolumab, as second-line treatment in mesothelioma. In addition, a third Phase II clinical trial will evaluate UV1 in a new cancer indication combined with indication-specific standard-of-care cancer therapies different from those tested in INITIUM (malignant melanoma, 154 patients) and NIPU (mesothelioma, 118 patients).
