The study will consist of two parts :
In the phase Ib: safety will be assessed in consecutive cohorts of 3 to 6 patients at increasing doses of TG4001 in combination with avelumab according to a 3+3 design. There will be no intra-patient dose escalation.
In the phase II part 1, evaluation of efficacy and further evaluation of safety of the combination of TG4001 and avelumab will be performed in a single arm of patients with recurrent or metastatic HPV-16 positive advanced malignancies.
In the phase II part 2, evaluation of efficacy of the combination of TG4001 and avelumab will be performed in a randomized, open-label controlled study comparing TG4001 in combination with avelumab to avelumab alone in patients with HPV-16 positive advanced malignancies.
In both phases, tumor response will be evaluated on local assessment using RECIST 1.1.
All patients will be followed up until disease progression, death, or unacceptable toxicity, or study withdrawal for any reason, whichever occurs first.

Start Date11 Sep 2017

Sponsor / Collaborator

Transgene SA

[+3]

NCT01022346 / CompletedPhase 2

A Randomized, Double-blind, Placebo-controlled, Parallel Group, Multicenter Study of the Safety and Response Rate of 3 Subcutaneously Administered Doses of 5 X 10^7 PFU RO5217790 in Patients With High Grade Cervical Intraepithelial Neoplasia Grade 2 or 3 Associated With High Risk HPV Infection

This randomized, double-blind, placebo-controlled, parallel arm study will assess the safety and the efficacy of RO5217790 on histologic resolution in participants with high grade CIN associated with HR-HPV infection. Participants will be randomized to receive 3 subcutaneous injections of either placebo or RO5217790 on Days 1, 8, and 15. Study assessments will be made at Baseline, at Month 3 and 6, and every 6 months thereafter for an overall of 2.5 years.

Start Date01 Aug 2009

Sponsor / Collaborator

Hoffmann-La Roche, Inc.

100 Clinical Results associated with Tipapkinogene sovacivec

100 Translational Medicine associated with Tipapkinogene sovacivec

100 Patents (Medical) associated with Tipapkinogene sovacivec

Literatures (Medical) associated with Tipapkinogene sovacivec

17 Dec 2024·JOURNAL OF VIROLOGY

Vaccine candidates based on MVA viral vectors expressing VP2 or VP7 confer full protection against Epizootic hemorrhagic disease virus in IFNAR(−/−) mice

Article

Author: Ortego, Javier ; Jiménez-Cabello, Luis ; Calvo-Pinilla, Eva ; Utrilla-Trigo, Sergio ; Rodríguez-Sabando, Karen ; Illescas-Amo, Miguel ; Carra-Valenzuela, Alejandro

ABSTRACT:

Epizootic hemorrhagic disease (EHD), caused by Epizootic hemorrhagic disease virus (EHDV), is an emerging and severe livestock disease. Recent incursion and distribution of EHDV in Europe have outlined the need for vaccine research against this viral disease. In this work, we report modified vaccinia virus Ankara (MVA)-vectored vaccines designed to express protein VP2 of EHDV-8 or protein VP7 of EHDV-2. Prime boost immunization of adult IFNAR(−/−) mice with the MVA-VP2 vaccine candidate induced high titers of EHDV-8-specific neutralizing antibodies (NAbs) and conferred full protection against homologous lethal challenge with EHDV-8. However, no heterologous protection was observed after lethal challenge with EHDV-6. In contrast, the MVA-VP7 vaccine candidate elicited strong cytotoxic CD8+ T-cell responses against VP7 and conferred complete protection against lethal challenge with either EHDV-8 or EHDV-6 in IFNAR(−/−) mice in the absence of NAbs, being the first multiserotype vaccine candidate against EHDV. Moreover, we expressed recombinant proteins VP2 and VP7 of EHDV in the baculovirus expression system, which were used to analyze the potential DIVA (differentiating infected from vaccinated animals) character of these vaccine candidates.

IMPORTANCE:

Emergence and re-emergence of arthropod-borne viruses are major concerns for both human and animal health. The most recent example is the fast expansion of EHDV-8 through Europe. Besides, EHDV-8 relates with a high prevalence of pathologic cases in cattle populations. No vaccine is currently available in Europe, and vaccine research against this arboviral disease is negligible. In this work, we present novel DIVA vaccine candidates against EHDV, and most importantly, we identified the protein VP7 of EHDV as an antigen capable of inducing multiserotype protection, one of the major challenges in vaccine research against orbiviruses.

01 Sep 2023·European journal of cancer (Oxford, England : 1990)

Phase Ib/II trial of tipapkinogene sovacivec, a therapeutic human papillomavirus16-vaccine, in combination with avelumab in patients with advanced human papillomavirus16-positive cancers

Article

Author: Piaggio, Eliane ; Capitain, Olivier ; Tavernaro, Annette ; Cyrta, Joanna ; Le Tourneau, Christophe ; Delord, Jean-Pierre ; Jeannot, Emmanuelle ; Castel-Ajgal, Zahra ; Marret, Grégoire ; Ekwegbara, Christina ; Makhloufi, Hakim ; Borcoman, Edith ; Brandely, Maud ; Rolland, Frédéric ; Bendjama, Kaidre ; Lalanne, Ana ; Cassier, Philippe A ; Salas, Sébastien ; Tran-Perennou, Carine ; Lantz, Olivier ; Limacher, Jean-Marc

PURPOSE:

To evaluate tipapkinogene sovacivec (TG4001), a viral immunotherapeutic vaccine expressing human papillomavirus (HPV)16 E6/E7 non-oncogenic proteins and IL-2, in combination with avelumab in HPV16+ cancer patients.

PATIENTS AND METHODS:

In this open-label, phase Ib/II, multicenter study, HPV16+ advanced cancer patients received subcutaneous TG4001 at two dose levels (DL) in phase Ib and at the recommended phase II dose (RP2D) in phase II weekly for 6 weeks, then every 2 weeks (q2Wk) until 6 months, thereafter every 12 weeks, in combination with avelumab q2Wk starting from day 8. Exploratory end-points included immunomonitoring from sequential tumour and blood samples.

RESULTS:

Forty-three patients, mainly heavily pretreated (88% ≥ 1 previous line), were included in the safety analysis, with a majority of anal cancer (44%). No dose-limiting toxicities were reported, and DL2 (5 × 10⁷ Plaque forming units (PFU)) was selected as the RP2D. Treatment-related adverse events to TG4001 occurred in 93% of patients, mostly grade 1/2, with grade 3 anaemia in one patient and no grade 4/5. Overall response rate (ORR) was 22% (8/36) and 32% (8/25) in all and patients without liver metastases, respectively. Median progression-free survival (PFS) and Overall Survival (OS) were 2.8 months (95% CI: 1.4-5.6) and 11.0 months (95% CI:7.5-16.7) in the total population and 5.6 months (95% CI:1.6-9.6) and 13.3 months (95% CI:8.7-32.7) in patients without liver metastases. Antigen-specific T-cell response was identified in 7/11 patients by IFNγ ELISpot.

CONCLUSIONS:

TG4001 in combination with avelumab is safe, demonstrated antitumour activity in heavily pre-treated HPV16+ cancer patients, and is currently being evaluated in a randomised phase II trial in patients with incurable anogenital cancer and limited hepatic involvement.

CLINICALTRIALS:

GOV IDENTIFIER:

NCT03260023.

01 Jun 2019·Gynecologic oncologyQ2 · MEDICINE

The efficacy and safety of Tipapkinogen Sovacivec therapeutic HPV vaccine in cervical intraepithelial neoplasia grades 2 and 3: Randomized controlled phase II trial with 2.5 years of follow-up

Q2 · MEDICINE

Article

Author: Glavini, Katerina ; Einstein, Mark H ; Bastien, Berangere ; Huh, Warner K ; Garcia, Francisco ; Harper, Diane M ; Nieminen, Pekka ; Attley, Gemma ; Calleja, Elizabeth ; Stoler, Mark H ; Donders, Gilbert ; Limacher, Jean-Marc

BACKGROUND:

While prophylactic human papillomavirus (HPV) vaccination exists, women are still developing cervical intraepithelial neoplasia (CIN) grade 2 or 3 for which an immunotherapeutic, non-surgical, approach may be effective. The primary aim was to assess the efficacy of tipapkinogen sovacivec (TS) vaccine in achieving histologic resolution of CIN2/3 associated with high risk (HR) HPV types.

METHODS:

Women 18 years and older who had confirmed CIN2/3 were enrolled in a randomized, double blind, placebo-controlled phase II trial and assigned to drug in a 2:1 ratio (vaccine:placebo). The primary endpoint occurred at month 6 when the excisional therapy was performed; cytology and HR HPV typing were performed at months 3, 6 and every six months through month 30. The safety population included all patients who received at least one dose of study drug.

RESULTS:

Of the 129 women randomized to vaccine and 63 to placebo, complete resolution was significantly higher in the vaccine group than placebo for CIN 2/3 regardless of the 13 HR HPV types assayed (24% vs. 10%, p < 0.05); as well as for only CIN 3 also regardless of HR HPV type (21% vs. 0%, p < 0.01). Irrespective of baseline HPV infection, viral DNA clearance was higher in the vaccine group compared to placebo (p < 0.01). The vaccine was well tolerated with the most common adverse events being injection site reactions.

CONCLUSIONS:

The TS vaccine provides histologic clearance of CIN 2/3 irrespective of HR HPV type in one third of subjects and is generally safe through 30 months.

News (Medical) associated with Tipapkinogene sovacivec

15 Oct 2024

·pipelinereview.com

Transgene Provides Update on Phase II Trial of Therapeutic Cancer Vaccine TG4001 in Recurrent or Metastatic HPV16-Positive Cervical and Anogenital Cancers

Top line data show that the randomized Phase II study of TG4001 in combination with avelumab versus avelumab alone in patients with recurrent or metastatic HPV16-positive cervical and anogenital tumors did not meet the primary objective of improvement in progression-free survival Pre-planned subgroup analysis showed a positive efficacy trend in favor of the TG4001 containing regimen in patients with cervical cancer Transgene will complete full analysis of the data before deciding on the best way forward for TG4001 STRASBOURG, France I October 14, 2024 I Transgene (Euronext Paris: TNG), a biotech company that designs and develops virus-based immunotherapies for the treatment of cancer, announces that its randomized Phase II study to evaluate TG4001 in combination with avelumab versus avelumab alone in patients with recurrent or metastatic HPV16-positive cervical and anogenital tumors has not met the primary objective of the study (improvement in progression-free survival). The pre-planned subgroup analysis showed a positive efficacy trend in favor of the TG4001 containing regimen in cervical cancer patients, which requires further confirmation through additional analyses, including by PD-L1 status. These patients account for approximately half of the patients enrolled in the study. The treatment has been well tolerated. Adverse events are consistent with previous observations. Transgene is currently evaluating the full study results in detail to determine the best way forward for this program and will communicate further once this is completed. Dr. Alessandro Riva, Chairman and CEO of Transgene , said: “Failure to meet the primary objective in our Phase II study with TG4001 is disappointing. Nevertheless, we are encouraged by the positive efficacy trend in favor of the combination regimen in cervical cancer patients. We plan to complete a full and rigorous analysis of the data before deciding on any path forward for this asset, in particular in cervical cancer, in the context of the evolving treatment landscape. The complete study results will be presented at an upcoming scientific conference. We would like to thank all the patients and caregivers who have taken part in this study for their important contribution. With a diversified portfolio of novel immunotherapies targeting solid tumors, our strategy remains focused on advancing our lead asset, TG4050, an individualized cancer vaccine for head and neck cancers for use following surgery and adjuvant therapy. We expect to report additional data on TG4050 from the 24-month median follow-up of Phase I patients in our head and neck cancer trial in November 2024 at the SITC conference.” A conference call in English is scheduled today, October 14, 2024, at 3:30 p.m. CET (9:30 p.m. ET). Webcast link to English language conference call: https://edge.media-server.com/mmc/p/zh5cy2u9/ Please log in to the following link to obtain your personal telephone IDs. A replay of the call will be available on the Transgene website (www.transgene.fr) following the live event. About TG4001 TG4001 (tipapkinogen sovacivec) is an investigational therapeutic vaccine based on a non-propagative, highly attenuated Vaccinia vector (MVA), which is engineered to express HPV16 antigens (E6 & E7) and an adjuvant (IL-2). TG4001 is designed to have a two-prolonged antiviral approach: to alert the immune system specifically to cells presenting the HPV16 E6 and E7 antigens, that can be found in HPV16-related tumors, and to further stimulate the infection-clearing activity of the immune system through interleukin 2 (IL-2). TG4001 has been administered to more than 350 individuals. Its mechanism of action and good safety profile make TG4001 an excellent candidate for combinations with other therapies in HPV-mediated solid tumors. About the trial TG4001 was evaluated in a multi-center, open label, randomized Phase II trial (NCT03260023) designed to compare the efficacy of the combination of TG4001 and avelumab versus avelumab alone in patients with recurrent or metastatic HPV16-positive cervical and anogenital cancers who have disease progression after a maximum of one line of systemic treatment, or who are not eligible for first-line chemotherapy. The overall trial enrolled 100 patients. About Transgene Transgene (Euronext: TNG) is a biotechnology company focused on designing and developing targeted immunotherapies for the treatment of cancer. Transgene’s programs utilize viral vector technology with the goal of indirectly or directly killing cancer cells. The Company’s clinical-stage programs consist of a portfolio of therapeutic vaccines and oncolytic viruses: TG4050, the first individualized therapeutic vaccine based on the myvac® platform, TG4001 for the treatment of HPV-positive cancers, as well as BT-001 and TG6050, two oncolytic viruses based on the Invir. IO® viral backbone. With Transgene’s myvac ® platform, therapeutic vaccination enters the field of precision medicine with a novel immunotherapy that is fully tailored to each individual. The myvac ® approach allows the generation of a virus-based immunotherapy that encodes patient-specific mutations identified and selected by Artificial Intelligence capabilities provided by its partner NEC. With its proprietary platform Invir. IO®, Transgene is building on its viral vector engineering expertise to design a new generation of multifunctional oncolytic viruses. Additional information about Transgene is available at: www.transgene.fr Follow us on social media: X (formerly Twitter): @TransgeneSA – LinkedIn: @Transgene SOURCE: Transgene

Clinical ResultVaccineImmunotherapyPhase 2Phase 1

15 Oct 2024

·www.pharmaceutical-technology.com

Transgene’s stock drops after Phase II cancer jab trial misses primary endpoint

Transgene’s Phase II trial of viral-based vaccine TG4001 failed to meet its primary endpoint. Credit: Kitsawet Saethao via Shutterstock. Transgene ’s stock has dropped after a Phase II trial of its therapeutic vaccine candidate TG4001 (tipapkinogene sovacivec) failed to meet its primary endpoint of improvement in progression-free survival (PFS) in solid tumours. Transgene’s share price fell 18.8% from €1.17 at close on 11 October to a low of €0.95 on Monday morning (14 October) after the announcement, settling at around €1 per share. The trial (NCT03260023) aimed to assess the impact of TG4001 in combination with Merck KgaA’s Bavencio (avelumab), a PD-L1 checkpoint inhibitor, in 150 patients with recurrent or metastatic HPV16-positive cervical and anogenital cancers who were either treatment-naïve or had one prior systemic chemotherapy, but no earlier immunotherapy. The addition of TG4001 did not produce statistically significant improvements in PFS across the study population, however, Transgene said it remains optimistic. In a subgroup of patients with cervical cancer – comprising about 54% of the trial population – the data suggested a potential trend towards improved PFS. The French biotech is planning further analysis, including examining the data by PD-L1 status, before deciding on the next steps for the candidate’s development. PD-L1 status refers to the level of expression of the PD-L1 protein on tumour cells, which can influence how well a patient’s cancer responds to Bavencio. See Also: Bayer applies for EU approval of menopause drug elinzanetant ENHERTU gains conditional approval in China to treat NSCLC TG4001, a viral-based vaccine, works by inducing an immune response against cells expressing the HPV16 E6 and E7 antigens, aided by the inclusion of human IL-2 to strengthen this immune reaction. In the announcement accompanying the data, Transgene’s CEO Alessandro Riva said: “Failure to meet the primary objective in our Phase II study with TG4001 is disappointing. Nevertheless, we are encouraged by the positive efficacy trend in favour of the combination regimen in cervical cancer patients.” Transgene said that it remains focused on its lead asset TG4050 , an individualised cancer vaccine that is in a Phase I/II trial (NCT04183166) in patients with head and neck cancer. TG4050 is based on Transgene’s myvac platform, which generates personalised therapies, based on patient-specific mutations (neoantigens), that are designed to induce a T cell response to tumour cells. The company expects to share 24-month data on Phase I patients in November at the Society for Immunotherapy of Cancer (SITC) conference. According to a GlobalData report , cancer vaccines are a key immuno-oncology development trend. TG4050 is a personalised vaccine, whereas TG4001 is an off-the-shelf standardised treatment. According to over half of high-prescribing key opinion leaders who responded to a GlobalData survey in 2023, personalised mRNA vaccines are the most promising cancer vaccine type. GlobalData is the parent company of Clinical Trials Arena. The company is also developing an oncolytic virus therapy, BT-001, for treating solid tumours in partnership with BioInvent International . The therapy is being evaluated in a Phase I/IIa clinical trial (NCT04725331) as a single agent and in combination with MSD’s PD-1 checkpoint inhibitor Keytruda (pembrolizumab). Transgene’s journey with oncolytic virus therapies has been challenging. In May 2023, AstraZeneca ended its four-year partnership with the company, a collaboration formed in 2019 with a $10m upfront payment to Transgene to develop oncolytic virus candidates. The partnership’s troubles started early, as one of Transgene’s candidates Pexa-Vec failed a Phase III trial (NCT02562755) just months after the deal was signed.

Phase 2VaccineDrug ApprovalImmunotherapyPhase 3

14 Oct 2024

·endpts.com

Transgene shares dip as therapeutic cancer vaccine disappoints in Phase 2 trial

Transgene’s therapeutic cancer vaccine candidate has failed a mid-stage test in certain HPV-driven cancers, sending its shares down around 14% Monday morning. The French biotech’s TG4001 plus Merck KGaA’s PD-L1 drug Bavencio did not meet the progression-free survival primary endpoint versus Bavencio alone in a Phase 2 study in people with recurrent or metastatic HPV16-positive cervical and anogenital cancers, according to a Monday release . But a planned subgroup analysis in patients with cervical cancer showed a positive efficacy trend in favor of the treatment cohort, the company said. Transgene CEO Alessandro Riva added it would run a “rigorous analysis” of the data before deciding if there’s a path forward for TG4001 in cervical cancer, taking into account the “evolving treatment landscape.” In March, Transgene announced it had completed the trial’s enrollment with 86 patients. The company plans to present the full data at an upcoming scientific conference. For now, Transgene said it is focused on advancing its lead therapeutic vaccine candidate, TG4050, for head and neck cancers. The biotech will present Phase 1 follow-up data on this asset at the Society for Immunotherapy of Cancer annual meeting next month. In June, Transgene said the first patient had been enrolled in the Phase 2 part of an ongoing Phase 1/2 study of TG4050. In May 2023, AstraZeneca walked away from an oncolytic virus pact with Transgene. At the end of June this year, the company reported just €15.3 million ($16.7 million) in cash and other financial assets and said it should have “financial visibility” through the end of 2025.

VaccinePhase 2Phase 1ImmunotherapyClinical Result

100 Deals associated with Tipapkinogene sovacivec

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R&D Status

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Indication	Highest Phase	Country/Location	Organization	Date
Human Papillomavirus-16 Positive	Phase 2	US	Transgene SA	11 Sep 2017
Human Papillomavirus-16 Positive	Phase 2	FR	Transgene SA	11 Sep 2017
Human Papillomavirus-16 Positive	Phase 2	ES	Transgene SA	11 Sep 2017
Human Papillomavirus-Related Anal Squamous Cell Carcinoma	Phase 2	US	Transgene SA	11 Sep 2017
Human Papillomavirus-Related Anal Squamous Cell Carcinoma	Phase 2	FR	Transgene SA	11 Sep 2017
Human Papillomavirus-Related Anal Squamous Cell Carcinoma	Phase 2	ES	Transgene SA	11 Sep 2017
Human Papillomavirus-Related Cervical Carcinoma	Phase 2	US	Transgene SA	11 Sep 2017
Human Papillomavirus-Related Cervical Carcinoma	Phase 2	FR	Transgene SA	11 Sep 2017
Human Papillomavirus-Related Cervical Carcinoma	Phase 2	ES	Transgene SA	11 Sep 2017
Human Papillomavirus-Related Squamous Cell Carcinoma of the Penis	Phase 2	US	Transgene SA	11 Sep 2017

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03260023 (Pubmed)	Phase 2	Human Papillomavirus-16 Positive	-	TG4001	xlbguvexdv(daqwxspttk) = beckwpiazb hfflsqjitt (lpgmzzrozp ) View more	-	11 Jul 2023
NCT03260023 (ASCO 12023 \| ASCO 22023) Manual	Phase 2	Neoplasms	40	Avelumab+TG4001	hxytxrbgcn(tgixgqgjcb) = xjvxmiebpy hrelwcupil (dylsdvaqja )	Positive	26 May 2023
NCT03260023 (ASCO 12023 \| ASCO 22023) Manual	Phase 2	Neoplasms	40	Avelumab	hxytxrbgcn(tgixgqgjcb) = bfaxwheerm hrelwcupil (dylsdvaqja )	Positive	26 May 2023
NCT03260023 (Biospace) Manual	Phase 1/2	Condylomata Acuminata	54	TG4001+Avelumab	aeuujypino(wvchsnkoev) = nedqrwdzly hltihpxkio (mfjtrywdzf ) View more	Positive	02 Nov 2022
NCT03260023 (SITC2020)	Phase 2	Human Papillomavirus-16 Positive	34	TG4001	wlggmlxhzq(epuvxfmtsb) = xqzitixfej dldeoyloea (cejwriklcf ) View more	Positive	09 Nov 2020
NCT01022346 (Pubmed) Manual	Phase 2	Cervical Intraepithelial Neoplasia	192	Tipapkinogen sovacivec	fmbyczgtuu(fzukppmzif) = The vaccine was well tolerated with the most common adverse events being injection site reactions. inegqftiuw (skraxdpahz ) View more	Positive	01 Jun 2019
NCT01022346 (Pubmed) Manual	Phase 2	Cervical Intraepithelial Neoplasia	192	Placebo		Positive	01 Jun 2019

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