- |||||||||| Imlygic (talimogene laherparepvec) / Amgen
Trial completion, Trial completion date, Metastases: TVEC and Preop Radiation for Sarcoma (4 ml Dose) (clinicaltrials.gov) - Jun 22, 2023
P1/2, N=30, Completed,
Active, not recruiting --> Completed | Trial completion date: Oct 2023 --> Mar 2023
- |||||||||| Imlygic (talimogene laherparepvec) / Amgen
Preclinical, Journal: Human Monocytes Are Suitable Carriers for the Delivery of Oncolytic Herpes Simplex Virus Type 1 In Vitro and in a Chicken Embryo Chorioallantoic Membrane Model of Cancer. (Pubmed Central) - Jun 14, 2023
An OV based on herpes simplex virus type 1 (oHSV-1), talimogene laherparepvec (T-VEC), has been recently approved by the Food and Drug Administration (FDA) and by the European Medicines Agency (EMA) for the treatment of unresectable melanoma...Moreover, human monocytic leukemia cells selectively delivered oHSV-1 to human head-and-neck xenograft tumors grown on the chorioallantoic membrane (CAM) of fertilized chicken eggs after intravascular injection. Thus, our work shows that monocytes are promising carriers for the delivery of oHSV-1s in vivo, deserving further investigation in animal models.
- |||||||||| Imlygic (talimogene laherparepvec) / Amgen, Provenge (sipuleucel-T) / Bausch Health
Journal: Vaccinating against cancer: getting to prime time. (Pubmed Central) - Jun 11, 2023
These represent the two approaches that have the most traction: vaccinating against cognate antigen and priming responses using tumors in situ. Here, we review the challenges and opportunities researchers face in developing therapeutic vaccines for cancer.
- |||||||||| Imlygic (talimogene laherparepvec) / Amgen, Yondelis (trabectedin) / Otsuka, PharmaMar, Valeo Pharma, Opdivo (nivolumab) / Ono Pharma, BMS
P2 data, Journal, Metastases: Activity of TNT: a phase 2 study using talimogene laherparepvec, nivolumab and trabectedin for previously treated patients with advanced sarcomas (NCT# 03886311). (Pubmed Central) - May 26, 2023
grade 3 treatment related adverse events which included anemia (6%), thrombocytopenia (6%), neutropenia (4%), increased alanine transaminase (4%), decreased left ventricular ejection fraction (4%), dehydration (4%), hyponatremia (4%). Taken together these data suggest that the TNT regimen is effective and safe for advanced previously treated sarcomas, and is worth being further studied in a randomized phase 3 trial as first- or second- line treatment for patients with advanced sarcomas.
- |||||||||| Imlygic (talimogene laherparepvec) / Amgen, Yondelis (trabectedin) / PharmaMar, J&J, Opdivo (nivolumab) / BMS
Trial completion date, Trial primary completion date: SOC-1882: Talimogene Laherparepvec, Nivolumab and Trabectedin for Sarcoma (clinicaltrials.gov) - May 18, 2023
P2, N=40, Recruiting,
Taken together these data suggest that the TNT regimen is effective and safe for advanced previously treated sarcomas, and is worth being further studied in a randomized phase 3 trial as first- or second- line treatment for patients with advanced sarcomas. Trial completion date: Mar 2023 --> Mar 2024 | Trial primary completion date: Dec 2022 --> Dec 2023
- |||||||||| Imlygic (talimogene laherparepvec) / Amgen
Enrollment closed, Trial completion date, Trial primary completion date: T-VEC With Chemotherapy or Endocrine Therapy in Treating Participants With HER2- Negative Breast Cancer (clinicaltrials.gov) - May 15, 2023
P1b, N=20, Active, not recruiting,
Trial completion date: Mar 2023 --> Mar 2024 | Trial primary completion date: Dec 2022 --> Dec 2023 Recruiting --> Active, not recruiting | Trial completion date: Apr 2024 --> Apr 2025 | Trial primary completion date: Apr 2024 --> Apr 2025
- |||||||||| Imlygic (talimogene laherparepvec) / Amgen, Yondelis (trabectedin) / Otsuka, PharmaMar, Valeo Pharma, Opdivo (nivolumab) / Ono Pharma, BMS
TNT: Talimogene Laherparepvec (An Oncolytic Virus Expressing GM-CSF), Nivolumab and Trabectedin for Advanced Leiomyosarcoma: A Phase 2 Study [NCT# 03886311] (Room 403 AB) - May 3, 2023 - Abstract #ASGCT2023ASGCT_2106;
The median PFS was 7 months (range: 3- 18; Trabectedin alone for LMS= 4.3 mos; Dacarbazine alone = 1.6 mos); 6-month PFS rate, 55%; median OS 18.2 months (range: 4- 32); 6-month OS rate, 91%. These results suggest that (1) By indirect comparison, the combination regimen using Talimogene laherparepvec, Nivolumab & Trabectedin may be more effective as second/third-line/fourth therapy for advanced leiomyosarcoma with manageable toxicity, (2) Response is not related to PD-L1 positivity and (3) The best responders are patients with HR+ uterine LMS.
- |||||||||| Imlygic (talimogene laherparepvec) / Amgen, Yondelis (trabectedin) / Otsuka, PharmaMar, Valeo Pharma, Opdivo (nivolumab) / Ono Pharma, BMS
Interim results of a phase 2 study using talimogene laherparepvec, nivolumab, and trabectedin for advanced leiomyosarcoma. (On Demand | Hall A; Poster Bd # 490) - Apr 26, 2023 - Abstract #ASCO2023ASCO_2819;
P2
These results suggest that (1) By indirect comparison, the combination regimen using Talimogene laherparepvec, Nivolumab & Trabectedin may be more effective as second/third-line/fourth therapy for advanced leiomyosarcoma with manageable toxicity (Trabectedin alone for LMS= 4.3 mos; Dacarbazine alone = 1.6 mos; Demetri 2015), and (2) The best responders are patients with HR+ uterine LMS. Clinical trial information: NCT03886311.
- |||||||||| Oncorine (recombinant human adenovirus type 5) / Mergen Ltd., Rigvir (ECHO-7) / Rigvir Group
Preclinical, Review, Journal, Oncolytic virus: Oncolytic virus preclinical toxicology studies. (Pubmed Central) - Apr 14, 2023
This article summarizes the preclinical toxicology studies of the most well studied oncolytic viruses, including Oncorine, Talimogene laherparepvec, Cavatak, ONYX-015, teserpaturev, and Rigvir, a non-pathogenic ECHO-7 virus. It is concluded that oncolytic viruses have been shown to have low toxicity and high tolerability in preclinical toxicology studies.
- |||||||||| Imlygic (talimogene laherparepvec) / Amgen, Keytruda (pembrolizumab) / Merck (MSD)
Combination of talimogene laherparepvec (T-VEC) with pembrolizumab (pembro) in advanced melanoma patients following progression on a prior PD-1 inhibitor: SWOG S1607 (Section 40; Poster Board #16) - Mar 14, 2023 - Abstract #AACR2023AACR_4674;
Translational study is ongoing for pharmacodynamic confirmation. T-VEC plus pembro in melanoma patients who have progressed on prior anti-PD1/L1 therapy has efficacy in the subset of melanoma patients who have non-visceral metastases.$$table_{B77E4652-270A-4849-8205-FBD28FD53F6E}$$Table 1Cohort A (Visceral)Cohort B(Non-Visceral)N (%; 95% CI)1127Confirmed PR + CR0 (0%; 0%-28%)7 (26%; 11%-46%)Confirmed + Unconfirmed1 (9%; 0%-41%)9 (33%; 17%-54%)Durable response0 (0%; 0%-28%)4 (15%; 4%-34%)Median PFS in months2.1 (0.7-5.5)2.3 (1.9-6.2)INJECTED LESIONS1127Confirmed PR + CR0 (0%; 0%-28%)6 (22%; 9%-42%)Confirmed + Unconfirmed, PR + CR1 (9%; 0%-41%)8 (30%; 14%-50%)NON-INJECTED, NON-VISCERAL LESIONS819Confirmed PR + CR0 (0%; 0%-37%)3 (16%; 3%-40%)Confirmed + Unconfirmed, PR + CR0 (0%; 0%-37%)5 (26%; 9%-51%)VISCERAL LESIONS11Confirmed PR + CR0 (0%; 0%-28%)Confirmed + Unconfirmed, PR + CR1 (9%; 0%-41%)ACQUIRED RESISTANCE32Confirmed PR + CR0 (0%; 0%-71%)2 (100%; 16%-100%)Confirmed + Unconfirmed, PR + CR0 (0%; 0%-71%)2 (100%; 16%-100%)Median PFS in months2.1 (2.0-4.1)NR (8.0-?)PRIMARY RESISTANCE825Confirmed PR + CR0 (0%; 0%-37%)5 (20%; 7%-41%)Confirmed + Unconfirmed, PR + CR1 (13%; 0%-53%)7 (28%; 12%-49%)Median PFS in months1.8 (0.3-6.2)2.1 (1.9-3.3)
- |||||||||| Imlygic (talimogene laherparepvec) / Amgen
Review, Journal, Metastases: Advances in Intralesional Therapy for Locoregionally Advanced and Metastatic Melanoma: Five Years of Progress. (Pubmed Central) - Mar 11, 2023
In 2015, the Food and Drug Administration (FDA) approved talimogene laherparepvec (T-VEC), the only FDA-approved intralesional therapy for advanced melanoma...This manuscript presents the various types of intralesional therapies that have reached phase 2 or later clinical trials in the past 5 years, including their mechanism of action, therapeutic combinations under investigation, and published results. The intention is to provide an overview of the progress that has been made, discuss ongoing trials worth following, and share our opinions on opportunities for further advancement.
- |||||||||| Imlygic (talimogene laherparepvec) / Amgen, Zolgensma (onasemnogene abeparvovec-xioi) / Novartis, Luxturna (voretigene neparvovec-rzyl) / Novartis, Roche
Variation in Medicaid and Commercial Coverage of Cell and Gene Therapies () - Mar 9, 2023 - Abstract #ISPOR2023ISPOR_145;
Medicaid and Commercial plans frequently use coverage restrictions beyond the FDA label for access to CGTs, however the use of restrictions varies depending on type of plan and CGT. We identified significant variation in coverage restrictions for CGTs both within and across Medicaid and Commercial plans, suggesting inconsistent patient access to these important therapies.
- |||||||||| Imlygic (talimogene laherparepvec) / Amgen
Review, Journal, Oncolytic virus: Therapy with oncolytic viruses: progress and challenges. (Pubmed Central) - Feb 27, 2023
These results support continued investigation of T-VEC plus NAC for TNBC. To date, four OVs and one non-oncolytic virus
- |||||||||| Imlygic (talimogene laherparepvec) / Amgen
Review, Journal, Oncolytic virus: The impact of oncolytic adenoviral therapy on the therapeutic efficacy of PD-1/PD-L1 blockade. (Pubmed Central) - Feb 26, 2023
Combination of oncolytic Ads with PD-1/PD-L1 inhibitors have shown potentials in promoting responses to ICIs, changing the tumor microenvironment, inducing long-term protection against tumor, and promoting survival among mice models of malignancies. Regarding the increasing importance of oncolytic Ads in combination therapy of cancers, in this review we decide to outline recent studies in this field.
- |||||||||| Imlygic (talimogene laherparepvec) / Amgen
Review, Journal: Talimogene Laherparepvec (T-VEC): A Review of the Recent Advances in Cancer Therapy. (Pubmed Central) - Feb 12, 2023
In addition, we will review the recent progress of T-VEC application in other cutaneous cancer types. Moreover, we will briefly describe our experience of T-VEC therapy at City of Hope, aiming to provide more insight for expanding its future application.
- |||||||||| Imlygic (talimogene laherparepvec) / Amgen
Trial completion date, Trial primary completion date: A Study of T-VEC (Talimogene Laherparepvec) With or Without Radiotherapy for Melanoma, Merkel Cell Carcinoma, or Other Solid Tumors (clinicaltrials.gov) - Feb 8, 2023
P2, N=19, Active, not recruiting,
Moreover, we will briefly describe our experience of T-VEC therapy at City of Hope, aiming to provide more insight for expanding its future application. Trial completion date: Jun 2023 --> Jun 2024 | Trial primary completion date: Jun 2023 --> Jun 2024
- |||||||||| Imlygic (talimogene laherparepvec) / Amgen
Intralesional T-VEC in cutaneous B-cell lymphoma (Room 4 (60 seats, First Floor)) - Jan 28, 2023 - Abstract #EADO2023EADO_213;
P1
The treatment was well tolerated without any unexpected toxicities in this patient population. T-VEC merits investigation in larger controlled clinical trials.
- |||||||||| Review, Journal: Neoadjuvant treatment for stage III and IV cutaneous melanoma. (Pubmed Central) - Jan 18, 2023
There is insufficient evidence to support the use of neoadjuvant treatment in clinical practice. Priorities for research include the development of a core outcome set for neoadjuvant trials that are adequately powered, with validation of pathological and radiological responses as intermediate endpoints, to investigate the relative benefits of neoadjuvant treatment compared with adjuvant treatment with immunotherapies or targeted therapies.
- |||||||||| Imlygic (talimogene laherparepvec) / Amgen
Trial completion date, Trial primary completion date: T-VEC With Chemotherapy or Endocrine Therapy in Treating Participants With HER2- Negative Breast Cancer (clinicaltrials.gov) - Jan 10, 2023
P1b, N=25, Recruiting,
Priorities for research include the development of a core outcome set for neoadjuvant trials that are adequately powered, with validation of pathological and radiological responses as intermediate endpoints, to investigate the relative benefits of neoadjuvant treatment compared with adjuvant treatment with immunotherapies or targeted therapies. Trial completion date: Apr 2023 --> Apr 2024 | Trial primary completion date: Apr 2023 --> Apr 2024
- |||||||||| Imlygic (talimogene laherparepvec) / Amgen
Journal, Oncolytic virus, Metastases: Oncolytic Viral Kinetics Mechanistic Modeling of Talimogene Laherparepvec (IMLYGIC®) a First-in-Class Oncolytic Viral Therapy in patients with Advanced Melanoma. (Pubmed Central) - Dec 25, 2022
Our analysis found 1) viral infection rate has great influence on T-VEC treatment efficacy, 2) an increase of T-VEC dose of 10 pfu/mL 21 days and beyond after the initial dose of T-VEC resulted in a ~12% increase in response; and 3) at the systemic level the ratio of resting innate immune cells to the death rate of innate immune impact T-VEC treatment efficacy. This analysis clarifies under which condition the immune system either assists in eliminating tumor cells or inhibits T-VEC treatment efficacy which is critical to both efficiently design future oncolytic agents and understanding cancer development.
- |||||||||| Imlygic (talimogene laherparepvec) / Amgen
Trial completion, Trial completion date, Metastases: Study of Talimogene Laherparepvec In Children With Advanced Non CNS Tumors (clinicaltrials.gov) - Dec 23, 2022
P1, N=15, Completed,
This analysis clarifies under which condition the immune system either assists in eliminating tumor cells or inhibits T-VEC treatment efficacy which is critical to both efficiently design future oncolytic agents and understanding cancer development. Active, not recruiting --> Completed | Trial completion date: Dec 2023 --> Nov 2022
- |||||||||| Review, Journal, Checkpoint inhibition, Tumor mutational burden, PD(L)-1 Biomarker, IO biomarker: Mechanisms of resistance to immune checkpoint inhibitors in melanoma: What we have to overcome? (Pubmed Central) - Dec 22, 2022
Reasonably, the primary and acquired resistance to ICIs has entered into the focus of clinical research with positive (e.g., nivolumab and relatlimab combination) and negative feedbacks (e.g., nivolumab with pegylated-IL2, pembrolizumab with T-VEC, nivolumab with epacadostat, and combinatorial triplets of BRAF/MEK inhibitors with immunotherapy)...In the present overview, we discuss how these parameters compromise the efficacy of ICIs, with an emphasis on the lessons learned by the latest melanoma studies; and in parallel, we describe the main ongoing approaches to overcome the resistance to immunotherapy. Summarizing this information will improve the understanding of how these complicated dynamics contribute to immune escape and will help to develop more effective strategies on how anti-tumor immunity can surpass existing barriers of ICI-refractory melanoma.
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