mesmulogene ancovacivec (TG4010) / Transgene - LARVOL DELTA

Advances in Non-Small Cell Lung Cancer Cellular Immunotherapy: A Progress in Dendritic Cell, T-Cell, and NK Cell Vaccines. (PubMed, Cells) - "T-cell vaccines, designed to activate cytotoxic CD8+ T-cell responses, have been tested across multiple platforms, including peptide-based (MAGE-A3), viral vector (TG4010/MUC1), and mRNA (CV9201/92) formulations. Recent advances include cytokine-enhanced, memory-like NK cells to overcome immunosuppression and "off-the-shelf" products for broader clinical use. Together, these cellular immunotherapies represent a versatile and evolving frontier in NSCLC treatment, with ongoing research optimizing combinations, delivery platforms, and patient selection to maximize therapeutic benefit."

Journal • Review • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CD8 • KRAS • MUC1

Therapeutic vaccines for advanced non-small cell lung cancer. (PubMed, Cochrane Database Syst Rev) - "Adding a vaccine resulted in no differences in overall survival, except for racotumomab, which showed some improvement compared to placebo, but the difference in median survival time was very small (1.4 months) and the study only included 176 participants. Regarding progression-free survival, we observed no differences between the compared treatments, except for TG4010, which may increase progression-free survival slightly. There were no differences between the compared treatments in serious treatment-related adverse events, except for SRL172 (killed Mycobacterium vaccae) added to chemotherapy, which was associated with an increase in the proportion of participants with at least one serious treatment-related adverse event, and OSE2101, which may decrease slightly the proportion of people having at least one serious treatment-related adverse event. These conclusions should be interpreted cautiously, as the very low- to moderate-certainty evidence prevents drawing solid ..."

Journal • Metastases • Review • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

A Study Evaluating the Efficacy and the Safety of First-line Chemotherapy Combined With the Therapeutic Vaccine Named TG4010 and Nivolumab in Patients With Advanced Non-squamous Non-Small Cell Lung Cancer (NSCLC) (clinicaltrials.gov) - P2; N=44; Completed; Sponsor: Transgene; Active, not recruiting ➔ Completed; Trial completion date: Nov 2020 ➔ Feb 2021

Clinical • Trial completion • Trial completion date • Lung Adenocarcinoma • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • MRI • PD-L1

TG4010 and Nivolumab in Patients With Lung Cancer (clinicaltrials.gov) - P2; N=13; Completed; Sponsor: Karen Kelly; Active, not recruiting ➔ Completed; N=33 ➔ 13; Trial completion date: Aug 2021 ➔ Feb 2021

Clinical • Enrollment change • Trial completion • Trial completion date • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • MRI

TG4010 and Nivolumab in Patients With Lung Cancer (clinicaltrials.gov) - P2; N=33; Active, not recruiting; Sponsor: Karen Kelly; Trial completion date: Oct 2020 ➔ Aug 2021; Trial primary completion date: Jun 2020 ➔ Feb 2021

Clinical • Trial completion date • Trial primary completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK

Vaccinia virus-mediated cancer immunotherapy: cancer vaccines and oncolytics. (PubMed, J Immunother Cancer) - "For instance, combination regimens using TG4010 (MVA-MUC1-IL2) with first-line chemotherapy in advanced-stage non-small cell lung cancer or combining PANVAC with docetaxel in the setting of metastatic breast cancer have clearly provided enhanced clinical benefits to patients...Encouraging translational and early phase clinical results with Pexa-Vec have matured into an ongoing global phase III trial for patients with hepatocellular carcinoma. Combinatorial approaches, most notably those using immune checkpoint blockade, have produced exciting pre-clinical results and warrant the development of innovative clinical studies. Finally, we discuss major hurdles that remain in the field and offer some perspectives regarding the development of next generation VV vectors for use as cancer therapeutics."

Journal • Review • Breast Cancer • Gastrointestinal Cancer • Hepatocellular Cancer • Immune Modulation • Inflammation • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Thoracic Cancer

Transgene: FY 2014 Results (Transgene) - Anticipated initiation of P2 trial in combination with ICIs in first line and second line NSCLC by Q1 2016

Anticipated new P2 trial • Non Small Cell Lung Cancer • Oncology

Transgene: Annual Results 2015 (Transgene) - "TG4010: PHASE 2B TIME TRIAL RESULTS"; "PHASE 3 TARGET POPULATION: NON-SQUAMOUS, LOW TrPAL"

P2b data • Non Small Cell Lung Cancer • Oncology

Transgene: Corporate Overview (Transgene) - Anticipated composition of matter patent and use claims patent expiries in 2016, 2017 and 2023; Anticipated expiry of patents covering biomarkers between 2029 and 2030; Anticipated expiry of manufacturing patent in 2027  

Anticipated patent expiry • Non Small Cell Lung Cancer

Transgene: Annual Results 2015 (Transgene) - Anticipated initiation of P1/2 trial in combination with nivolumab in second-line stage IV NSCLC in US in H2 2016; Anticipated initiation of P1/2 trial in combination with an ICI and chemotherapy in first-line stage IV NSCLC in Europe in H2 2016; Anticipated initiation of P1/2 trial in early stage NSCLC (neo-adjuvant setting) in Europe in H2 2016

Anticipated new P1/2 trial • Non Small Cell Lung Cancer • Oncology

TG4010 and nivolumab in patients with lung cancer (clinicaltrials.gov) - KEE: Karen Kelly; P2, N=33; Not yet recruiting.

New P2 trial • US NSCLC KEE

First patient dosed in a phase 2 trial with Transgene’s TG4010 + nivolumab + chemotherapy for the first-line treatment of lung cancer (NSCLC) (Businesswire) - P2, N=39; NCT03353675; "Transgene...announces the dosing of the first patient in the Phase 2 trial evaluating TG4010 in combination with Opdivo® (nivolumab) and chemotherapy as a first-line treatment for advanced non-squamous non-small cell lung cancer (NSCLC) with low or no expression of PD-L1 by the tumor cells....The first results are expected in H2 2018."

Trial status • Non Small Cell Lung Cancer • Oncology

Transgene presents 2018 half-year results and business update [NCT02823990] (Businesswire) - P2, N=33; NCT02823990; "Trial of TG4010 in combination with nivolumab [for NSCLC – 2nd line]...The prevailing use of ICIs in first-line therapy in the USA has led to a very significant slowdown in the recruitment of this trial, as patients previously treated with ICIs are excluded per protocol...the trial will be discontinued due to poor patient accrual....No unexpected safety issues have been observed."

Enrollment status • P2 data • Trial termination • Lung Cancer • Non Small Cell Lung Cancer • Oncology

TIME, a phase 2b/3 study evaluating TG4010 in combination with first line therapy in advanced non-small cell lung cancer (NSCLC). Phase 2b results (CMSTO 2014) - Abstract #172; P2b, N=217; NCT01383148; Sponsor: Transgene; "TG4010 related adverse events were limited to mild or moderate fever and injection site reaction....Additional pre-planned analyses by subgroup show that patients with non-squamous tumors had a statistically significant improvement in PFS when treated with TG4010 (n=145, HR=0.67; CI: 0.46-0.97; p=0.016) and especially when belonging to the three lowest quartiles (n=131, HR=0.63; 95% CI: 0.42-0.93, p=0.009)."

P2 data • Non Small Cell Lung Cancer • Oncology

Transgene announces publication in “The Lancet Oncology” of phase 2b TIME trial results with TG4010 immunotherapy in non-small cell lung cancer (Transgene Press Release) - P2b, N=222; TIME (NCT01383148); Sponsor: Transgene;  "...improvements were seen in progression-free survival, overall survival, response rate and duration of response in the TG4010 group compared to control, and these improvements were even more notable in patients with a “low” level of the triple positive activated lymphocytes (TrPAL1) biomarker, as well as in those patients with both low TrPAL and non-squamous disease. TG4010 was well tolerated, and the nature and incidence of adverse events in the TG4010 arm were consistent with previous Phase 2 clinical trials."

P2b data • Non Small Cell Lung Cancer • Oncology

Transgene announces topline preliminary results from phase 2b part of TIME trial with TG4010 in non-small cell lung cancer (Transgene Press Release) - P2, N=210; Sponsor: Transgene; NCT01383148; “…larger improvement in PFS was obtained in patients with non-squamous tumors not treated  with bevacizumab (73% of initial study population); in general this is a large and growing subgroup of NSCLC and so will warrant further investigation. TG4010 was well tolerated, and the nature and incidence of adverse events in the TG4010 arm were consistent with previous Phase 2 clinical trials. The data from the trial continue to mature; detailed results are expected to be presented at major medical meetings during 2014."

Anticipated P2 data • P2 data • Non Small Cell Lung Cancer

TG4010 immunotherapy combined with first-line chemotherapy in advanced non-small cell lung cancer (NSCLC). Phase 2B results of the time study (ELCC 2015) - Abstract #105PD; P2/3, N=221; NCT01383148; Sponsor: Transgene; "PFS analysis shows a HR of 0.66 (95% CI: 0.46-0.96, p = 0.014). Sub-group analysis in patients with non-squamous tumors show also a statistically significant improvement in PFS when treated with TG4010 (n = 195, HR = 0.71; CI: 0.51-0.97; p = 0.016). In the whole study population RR was 39.1% with TG4010 versus 28.8% with placebo ( p = 0.03)."

P2/3 data • Non Small Cell Lung Cancer • Oncology

Transgene: Corporate Overview (Transgene) - “TG4010: PHASE 2B TIME TRIAL RESULTS”; “Primary objective: PFS to prospectively validate the TrPAL predictive biomarker: As recommended by the FDA, primary endpoint based on a Bayesian design: pooling PFS data from TIME Phase 2b trial and earlier study in NSCLC to accelerate time to results and with fewer patients”; “In Normal TrPAL group, probability that TG4010 induces reduction in disease progression or death - i.e., hazard ratio (HR) <1 is 98.6%: Thus, Phase 2b part of TIME study after 144 events of progression passes Bayesian probability threshold of 95%”; “In High TrPAL group, number of events needed to perform primary analysis not yet reached”; “All other analyses in study based on traditional Frequentist approach”

P2 data • Non Small Cell Lung Cancer

Transgene: Corporate Presentation (Transgene) - Anticipated preliminary data from P2 trial (NCT02823990) of TG4010 in combination with nivolumab for 2L NSCLC in 2017

Anticipated P2 data • Non Small Cell Lung Cancer • Oncology

Transgene: UC Davis to conduct phase 2 trial of the combination of TG4010 with Opdivo (nivolumab) for 2nd Line Treatment of Metastatic Non-Small Cell Lung Cancer (NSCLC) (Businesswire) - "Transgene...announced the signature of a collaborative arrangement with UC Davis (USA, California) to support an investigator-initiated study led UC Davis Medical Center that will evaluate TG4010 in combination with Opdivo® (nivolumab) for the treatment of 2nd line metastatic non-small cell lung cancer (NSCLC)....The enrollment of the first patients is expected in the coming weeks."

Anticipated new P2 trial • Licensing / partnership • Non Small Cell Lung Cancer • Oncology

TIME, a phase 2b/3 study evaluating TG4010 in combination with first line therapy in advanced non small cell lung cancer (NSCLC). Phase 2b results (ESMO 2014) - Presentation time: 28.09.2014, 13:00 - 14:00; Abstract #1055PD; P2/3, N=217; Sponsor: Transgene; NCT01383148; “Additional pre-planned analyses by subgroup show that patients with non-squamous tumors had a statistically significant improvement in PFS when treated with TG4010 (n=145, HR=0.67; CI: 0.46-0.97; p=0.016) and especially when belonging to the three lowest quartiles (n=131, HR=0.63; 95% CI: 0.42-0.93, p=0.009). Overall survival data will be presented at the time of the meeting.” 

P2/3 data • Non Small Cell Lung Cancer • Oncology

TG4010 and nivolumab in patients with lung cancer (clinicaltrials.gov) - P2, N=33; Not yet recruiting ➔ Recruiting; Trial initiation date: Aug 2016 ➔ Dec 2016.

Enrollment open • Trial initiation date

Transgene: H1 2014 Results (Transgene) - Anticipated updated data from P2 TIME trial for advanced non-small cell lung cancer at ESMO 2014 (Sep 26-30, 2014) 

Anticipated P2 data • Non Small Cell Lung Cancer

Results of the phase IIb part of TIME study evaluating TG4010 immunotherapy in stage IV non-small cell lung cancer (NSCLC) patients receiving first line chemotherapy (ASCO 2015) - Presentation time: Saturday, May 30; 8:00 AM - 11:30 AM; Abstract #3034; P2b, N=222; NCT01383148; Sponsor: Transgene; "PFS was significantly improved in the TG4010 arm in pts with low TrPAL (152 pts HR = 0.66 [CI95% 0.46-0.95] p = 0.013) while it was not the case in pts with high TrPAL (70 pts HR = 0.97 [CI 95% 0.55-1.73] p = 0.463). In addition, PFS was also significantly improved in pts with non-squamous tumors (196 pts HR = 0.69 [CI95% 0.51-0.94] p = 0.009) as well as in pts with non-squamous tumors and low TrPAL (131 pts HR = 0.61 [CI95% 0.42-0.89] p = 0.005)."

P2b data • Non Small Cell Lung Cancer • Oncology

Transgene: Corporate Overview (Transgene) - Anticipated data from P2b part of TIME trial (NCT01383148) for NSCLC at ASCO (May 29 – June 2, 2015); Anticipated initiation of P3 part of TIME trial (NCT01383148) for NSCLC by Q1 2016

Anticipated P2b data • Anticipated trial initiation date • Non Small Cell Lung Cancer