On November 29, 2023 AbbVie (NYSE: ABBV) reported topline results from the single-arm Phase 2 LUMINOSITY trial evaluating telisotuzumab-vedotin (Teliso-V) in patients with c-Met protein overexpression, epidermal growth factor receptor (EGFR) wild type, advanced/metastatic nonsquamous non-small cell lung cancer (NSCLC) (Press release, AbbVie, NOV 29, 2023, View Source [SID1234638055]). The results demonstrated a compelling overall response rate per independent central review (ICR) of 35 percent and 23 percent across c-Met High and c-Met Intermediate patients respectively.

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In addition, other endpoints demonstrated meaningful clinical outcomes including median duration of response per ICR of 9 months and 7.2 months and a median overall survival of 14.6 months and 14.2 months across c-Met High and c-Met Intermediate patients respectively.

The safety profile of Teliso-V was consistent with previous findings and no new safety concerns were identified. Adverse events with Teliso-V monotherapy were generally well managed and tolerated. Full data from the LUMINOSITY study will be presented at a future medical meeting and we will discuss with global health authorities the potential to support an accelerated approval.

Approximately 85% of lung cancers are classified as NSCLC1 and despite advances in treatment, lung cancer remains the leading cause of cancer-related deaths in both men and women throughout the world.2 C-Met protein overexpression is found in approximately 25% of advanced EGFR wild type NSCLC patients3 and is associated with a poor prognosis for these patients.4,5,6 Teliso-V, an investigational ADC, is being studied in this patient population who have very limited treatment options and where there are currently no approved therapies.

"The results of the Phase 2 LUMINOSITY trial are encouraging for those patients with non-small cell lung cancer with c-Met overexpression as there is a critical need for better care and additional therapy options for them," said Ross Camidge, MD, PhD, University of Colorado Cancer Center, United States, and Principal Investigator for the trial. "Today’s announcement also provides confidence as we continue to enroll patients into the Phase 3 TeliMET NSCLC-01 trial and expand our understanding of Teliso-V’s potential."

"Results from the Phase 2 LUMINOSITY trial mark an important step forward for AbbVie’s mission to advance new oncology treatments across our ADC program targeting solid tumor types with critical patient needs," said Roopal Thakkar, M.D., senior vice president, development and regulatory affairs and chief medical officer, AbbVie.

Teliso-V is being evaluated as a monotherapy in patients with previously treated c-Met overexpressing EGFR wild type nonsquamous NSCLC in the randomized Phase 3 study TeliMET NSCLC-01, which is currently enrolling.

Teliso-V has also been granted several designations around the world including Breakthrough Therapy Designation (BTD) by the U.S. Food and Drug Administration (FDA) and Taiwanese health authorities, SAKIGAKE designation in Japan by the Ministry of Health, Labour and Welfare (MHLW), as well as being awarded an Innovation Passport by the UK’s Medicines and Healthcare products Regulatory Agency (MHRA).

About Telisotuzumab-Vedotin (Teliso-V)
Teliso-V is an investigational first-in-class, c-Met protein directed antibody-drug conjugate (ADC) targeting patients with c-Met overexpressing tumors. C-Met is a receptor tyrosine kinase that is overexpressed in many solid tumors including NSCLC. Teliso-V is being evaluated as a monotherapy in patients with previously treated c-Met overexpressing EGFR wild type non squamous NSCLC in the randomized Phase 3 study TeliMET NSCLC-01, which is currently enrolling. In addition, it is being evaluated in combination with osimertinib in the ongoing Phase 1 study M14-237, and as a monotherapy in the Phase 2 LUMINOSITY study. Further information on clinical trials for Teliso-V is available at View Source Currently there are no approved cancer therapies specifically for patients with c-Met overexpressing NSCLC. Teliso-V is not approved by any regulatory authority and its safety and efficacy have not been established.

About the LUMINOSITY trial
The LUMINOSITY trial (M14-239), is an ongoing Phase 2 study designed to identify the target NSCLC populations that overexpress c-Met best suited for Teliso-V monotherapy in the second line or third line setting, and then to expand the groups to further evaluate efficacy in the selected populations. The endpoints include overall response rate (ORR), duration of response (DoR), disease control rate (DCR) and progression-free survival (PFS) per independent central review (ICR) as well as overall survival (OS).

On November 29, 2023 Telix Pharmaceuticals Limited (ASX: TLX, Telix, the Company) reported that the completed Phase II OPALESCENCE investigator-initiated trial (IIT) of its carbonic anhydrase IX (CAIX)-targeting positron emission tomography (PET) imaging candidate, TLX250-CDx (89Zr-DFO-girentuximab), in patients with triple-negative breast cancer (TNBC), will be presented at the 2023 San Antonio Breast Cancer Symposium (SABCS) taking place from December 5-9, 2023 (Press release, Telix Pharmaceuticals, NOV 29, 2023, View Source [SID1234638054]).

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Dr. Caroline Rousseau, Principal Investigator for the OPALESCENCE study (ClinicalTrials.gov ID NCT04758780) at the Institut de Cancérologie de l’Ouest (ICO) in St Herblain (France), will deliver top-line results as a poster presentation at 5pm CT on Wednesday December 6.

The primary objective of the OPALESCENCE study was to evaluate how CAIX-targeted imaging with PET can be utilised for the diagnosis and staging of TNBC and to develop a deeper understanding of CAIX as a potential therapeutic target in this patient population with a significant unmet medical need.

SABCS is the largest and most prestigious scientific gathering on breast cancer research worldwide. Visit View Source for more information on the congress.

On November 29, 2023 Adaptimmune Therapeutics plc (NASDAQ: ADAP), a leader in cell therapy to treat cancer, reported the transfer of the IND for letetresgene autoluecel (lete-cel) from GSK to Adaptimmune for the pivotal IGNYTE-ESO (NCT03967223) clinical trial (Press release, Adaptimmune, NOV 29, 2023, View Source [SID1234638053]).

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Adrian Rawcliffe, Adaptimmune’s Chief Executive Officer: "The compelling clinical data from the pivotal IGNYTE-ESO trial frames lete-cel as the ideal synergistic product to afami-cel and could enable our sarcoma franchise to more than double the addressable patient population. Further, we can deliver lete-cel to market efficiently using the same commercial footprint we intend to use for afami-cel."

Adaptimmune recently reported data from a protocol-defined interim analysis of the pivotal IGNYTE-ESO trial. In this analysis, 40% (18/45) of people with synovial sarcoma or myxoid/ round cell liposarcoma (MRCLS) had confirmed clinical responses with lete-cel by independent review. The primary efficacy endpoint requires 16/60 patients have responses. As a result, the Company is evaluating the integration of lete-cel into its sarcoma franchise and is looking forward to sharing its development plans for lete-cel in the new year.

Lete-cel, an engineered TCR T-cell therapy targeting the solid tumor antigen NY-ESO-1, was originally developed by Adaptimmune, and further developed under a collaboration and license agreement with GSK plc. Lete-cel is being investigated for the treatment of synovial sarcoma or myxoid/round cell liposarcoma (MRCLS) in the pivotal IGNYTE-ESO (NCT03967223) trial in patients who received prior anthracycline treatment. In 2023, Adaptimmune and GSK agreed terms regarding the return of the NY-ESO program back to Adaptimmune. Per the terms of the Agreement, Adaptimmune has received an upfront amount and will receive milestone-based payments totaling £30 million in relation to the transfer of the clinical trials for the NY-ESO targeted programs.

About synovial sarcoma

There are approximately 50 types of soft tissue sarcomas which are categorized by tumors that appear in fat, muscle, nerves, fibrous tissues, blood vessels, or deep skin tissues.1 Synovial sarcoma accounts for approximately 5% to 10% of all soft tissue sarcomas (there are approximately 13,400 new soft tissue cases in the U.S. each year).2 One third of patients with synovial sarcoma will be diagnosed under the age of 30.2 The five-year survival rate for people with metastatic disease is just 20% and most people undergoing standard of care treatment for advanced disease experience recurrence and go through multiple lines of therapy, often exhausting all options.3

1. View Source accessed Oct. 24, 2023
2. Synovial Sarcoma – NCI (cancer.gov) accessed Oct. 24, 2023
3. Aytekin MN, et al. J Orthop Surg (Hong Kong). 2020;28(2)

About Myxoid/round cell liposarcoma (MRCLS)

Myxoid/round cell liposarcoma (MRCLS) is a type of soft tissue sarcoma that is predominantly found in the limbs. MRCLS accounts for approximately 5% to 10% of all soft tissue sarcomas.1 One-third of MRCLS cases will become metastatic with tumors spreading to unusual bone and soft tissue locations. MRCLS commonly presents at an age ranging from 35-55 years and has a poor prognosis because it recurs locally and tends to metastasize quickly and widely. The 5-year survival rate for metastatic MRCLS is only 5%.2

1. View Source accessed Oct. 24, 2023
2. https: www.orpha.net accessed Oct. 24, 2023

Overview of IGNYTE-ESO trial design

IGNYTE-ESO is a Phase 2, open-label trial for people with advanced synovial sarcoma or MRCLS to evaluate the efficacy, safety, and tolerability of lete-cel. Lete-cel’s engineered TCR T-cells target NY-ESO-1+ tumors. NY-ESO-1 is highly expressed in synovial sarcoma and MRCLS in the context of HLA-A*02.

Key eligibility criteria include ECOG performance status of 0 or 1; HLA*02 positive with confirmed NY-ESO expression in ≥ 30% of tumor cells ≥ 2+ by immunohistochemistry; aged ≥ 10 years; and patients must have measurable disease according to RECIST v1.1 at the time of treatment. The IGNYTE-ESO master protocol include two substudies – Substudy 1 was designed to investigate lete-cel in previously untreated advanced (metastatic or unresectable) synovial sarcoma or MRCLS; and Substudy 2 was designed to investigate lete-cel in advanced (metastatic or unresectable) synovial sarcoma or MRCLS post-anthracycline chemotherapy. Eligible patients received lete-cel doses between 1-15 × 10^9 transduced T-cells after receiving lymphodepleting chemotherapy.

Approximately 10 people were planned to be treated in Substudy 1, 5 patients were treated and enrollment was stopped. Approximately 60 people were planned to be treated in Substudy 2 and enrollment is complete.

On November 29, 2023 Adaptimmune Therapeutics plc (NASDAQ: ADAP), a leader in cell therapy to treat cancer, reported the transfer of the IND for letetresgene autoluecel (lete-cel) from GSK to Adaptimmune for the pivotal IGNYTE-ESO (NCT03967223) clinical trial (Press release, Adaptimmune, NOV 29, 2023, View Source [SID1234638053]).

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Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

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Adrian Rawcliffe, Adaptimmune’s Chief Executive Officer: "The compelling clinical data from the pivotal IGNYTE-ESO trial frames lete-cel as the ideal synergistic product to afami-cel and could enable our sarcoma franchise to more than double the addressable patient population. Further, we can deliver lete-cel to market efficiently using the same commercial footprint we intend to use for afami-cel."

Adaptimmune recently reported data from a protocol-defined interim analysis of the pivotal IGNYTE-ESO trial. In this analysis, 40% (18/45) of people with synovial sarcoma or myxoid/ round cell liposarcoma (MRCLS) had confirmed clinical responses with lete-cel by independent review. The primary efficacy endpoint requires 16/60 patients have responses. As a result, the Company is evaluating the integration of lete-cel into its sarcoma franchise and is looking forward to sharing its development plans for lete-cel in the new year.

Lete-cel, an engineered TCR T-cell therapy targeting the solid tumor antigen NY-ESO-1, was originally developed by Adaptimmune, and further developed under a collaboration and license agreement with GSK plc. Lete-cel is being investigated for the treatment of synovial sarcoma or myxoid/round cell liposarcoma (MRCLS) in the pivotal IGNYTE-ESO (NCT03967223) trial in patients who received prior anthracycline treatment. In 2023, Adaptimmune and GSK agreed terms regarding the return of the NY-ESO program back to Adaptimmune. Per the terms of the Agreement, Adaptimmune has received an upfront amount and will receive milestone-based payments totaling £30 million in relation to the transfer of the clinical trials for the NY-ESO targeted programs.

About synovial sarcoma

There are approximately 50 types of soft tissue sarcomas which are categorized by tumors that appear in fat, muscle, nerves, fibrous tissues, blood vessels, or deep skin tissues.1 Synovial sarcoma accounts for approximately 5% to 10% of all soft tissue sarcomas (there are approximately 13,400 new soft tissue cases in the U.S. each year).2 One third of patients with synovial sarcoma will be diagnosed under the age of 30.2 The five-year survival rate for people with metastatic disease is just 20% and most people undergoing standard of care treatment for advanced disease experience recurrence and go through multiple lines of therapy, often exhausting all options.3

1. View Source accessed Oct. 24, 2023
2. Synovial Sarcoma – NCI (cancer.gov) accessed Oct. 24, 2023
3. Aytekin MN, et al. J Orthop Surg (Hong Kong). 2020;28(2)

About Myxoid/round cell liposarcoma (MRCLS)

Myxoid/round cell liposarcoma (MRCLS) is a type of soft tissue sarcoma that is predominantly found in the limbs. MRCLS accounts for approximately 5% to 10% of all soft tissue sarcomas.1 One-third of MRCLS cases will become metastatic with tumors spreading to unusual bone and soft tissue locations. MRCLS commonly presents at an age ranging from 35-55 years and has a poor prognosis because it recurs locally and tends to metastasize quickly and widely. The 5-year survival rate for metastatic MRCLS is only 5%.2

1. View Source accessed Oct. 24, 2023
2. https: www.orpha.net accessed Oct. 24, 2023

Overview of IGNYTE-ESO trial design

IGNYTE-ESO is a Phase 2, open-label trial for people with advanced synovial sarcoma or MRCLS to evaluate the efficacy, safety, and tolerability of lete-cel. Lete-cel’s engineered TCR T-cells target NY-ESO-1+ tumors. NY-ESO-1 is highly expressed in synovial sarcoma and MRCLS in the context of HLA-A*02.

Key eligibility criteria include ECOG performance status of 0 or 1; HLA*02 positive with confirmed NY-ESO expression in ≥ 30% of tumor cells ≥ 2+ by immunohistochemistry; aged ≥ 10 years; and patients must have measurable disease according to RECIST v1.1 at the time of treatment. The IGNYTE-ESO master protocol include two substudies – Substudy 1 was designed to investigate lete-cel in previously untreated advanced (metastatic or unresectable) synovial sarcoma or MRCLS; and Substudy 2 was designed to investigate lete-cel in advanced (metastatic or unresectable) synovial sarcoma or MRCLS post-anthracycline chemotherapy. Eligible patients received lete-cel doses between 1-15 × 10^9 transduced T-cells after receiving lymphodepleting chemotherapy.

Approximately 10 people were planned to be treated in Substudy 1, 5 patients were treated and enrollment was stopped. Approximately 60 people were planned to be treated in Substudy 2 and enrollment is complete.

On November 29, 2023 G1 Therapeutics, Inc. (Nasdaq: GTHX), a commercial-stage oncology company, reported that an abstract exploring the long-term impact of trilaciclib on survival outcomes in patients with metastatic triple negative breast cancer (mTNBC) from the Company’s Phase 2 trial (NCT02978716) will be presented in a poster session during the upcoming 2023 San Antonio Breast Cancer Symposium (SABCS), held December 5th through 9th in San Antonio, TX (Press release, G1 Therapeutics, NOV 29, 2023, View Source [SID1234638052]). A copy of the poster will be made available on the G1 Therapeutics website following the presentation here.

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Results in the poster include:

Median overall survival (OS) for patients who received subsequent lines of anticancer therapy (SACT) after discontinuation of study treatment was 32.7 months for patients who had previously received trilaciclib prior to gemcitabine/carboplatin (GCb) compared to 12.8 months for patients who had previously received GCb only (no trilaciclib), with increasing separation of survival curves over time.
Improved survival and sustained separation of curves was also observed in patients unable to receive SACT, although the magnitude of benefit was smaller (median 9.4 months for patients who had previously received trilaciclib vs 5.4 months for patients who had previously received chemotherapy alone).
Notably, median OS from the start of the first SACT was 14.0 months in patients who had previously received trilaciclib prior to GCb compared to 5.8 months in patients who received GCb only (no trilaciclib).
For patients who received any SACT after discontinuation of study treatment, demographics and clinical characteristics including, time from end of study treatment to first SACT, and type of SACT were balanced between the prior trilaciclib (n=43) and prior GCb-only (n=20) groups.
"These results describe the long-term survival benefits of treatment with trilaciclib in patients with triple negative breast cancer that participated in our Phase 2 trial," said Raj Malik, M.D., Chief Medical Officer of G1 Therapeutics. "The survival benefit appears to extend well beyond the initial treatment with trilaciclib and chemotherapy. Importantly, patients who had previously received trilaciclib continue to benefit with subsequent therapies, resulting in substantially longer survival than patients who had previously received chemotherapy alone. We believe this is likely due to preservation of bone marrow and immune function, resulting in improved long term immune surveillance. We look forward to sharing these results with the oncology community, as we assess the impact of trilaciclib on overall survival in our ongoing pivotal Phase 3 mTNBC and Phase 2 ADC trials."

Poster Presentation Details:
Patients With Metastatic Triple-Negative Breast Cancer who Receive Trilaciclib Prior to Cytotoxic Chemotherapy Exhibit Improved Survival After Receiving Subsequent Anticancer Therapy. O’Shaughnessy, J. et al.
Presentation ID (poster and abstract number): PO2-06-12.
Poster Session 2
Wednesday, December 6, 2023. 5:00 PM – 7:00 PM CDT