On September 16, 2024 Immutep Limited, a clinical-stage biotechnology company developing novel LAG-3 immunotherapiesfor cancer and autoimmune disease, reported positive efficacy and safety results from the TACTI-003 Phase IIb trial evaluating eftilagimod alpha (efti) in combination with MSD’s (Merck & Co., Inc., Rahway, NJ, USA) antiPD-1 therapy KEYTRUDA (pembrolizumab) as first-line treatment of recurrent or metastatic head and neck squamous cell carcinoma patients (1L HNSCC) (Press release, Immutep, SEP 16, 2024, View Source [SID1234646626]).

Schedule your 30 min Free 1stOncology Demo!
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

                  Schedule Your 30 min Free Demo!

These results with a data cut-off of 11 March 2024 were selected as a Proffered Paper oral presentation at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2024 and were presented by Claus Kristensen, M.D., Ph.D., Head of Section for Thoracic and Head and Neck Oncology, Rigshospitalet, Copenhagen, Denmark, on 15 September. The data adds to the previously reported overall response rates and safety data on 27 June and 12 July.

Dr. Kristensen stated, "The efficacy and safety data in TACTI-003 are very encouraging and show the significant potential of this novel immunotherapy combination to fight difficult-to-treat head and neck squamous cell carcinomas. The clinically meaningful improvement in responses for patients with high PD-L1 expression in the randomised portion of the trial, combined with the compelling response rates in patients with no PD-L1 expression, are a testament to the complementary nature of efti in combination with KEYTRUDA. I am particularly impressed that these higher response rates and clear increase in biological activity seen in the efti arm do not come at the expense of durability of response or lead to an increased toxicity profile, which is often the case when combining therapies in the search for more efficacious treatments for cancer patients."

Dr. Frédéric Triebel, CSO of Immutep, said "Through multiple clinical trials, we see the promise of efti to not only improve cancer patients’ clinical responses to immune checkpoint inhibitors, but also to expand patient populations who respond to them including patients with negative PD-L1 expression. Once again, the TACTI003 trial has reinforced efti’s positive impact on both these fronts. We are excited to see efti in combination with KEYTRUDA now driving a 1.9-fold increase in responses for head and neck cancer patients with high PDL1 expression as compared to KEYTRUDA alone, and a statistically significant increase in absolute lymphocyte count in the treatment arm showing efti’s biological activity in a randomised setting."

Marc Voigt, CEO of Immutep, added "As we move into the latter half of 2024, we will continue to follow the data in TACTI-003 and start to engage with regulatory authorities regarding potential paths forward. We are certainly pleased with durability we are seeing, which is consistent with other trials in which efti combined with KEYTRUDA achieves a high DOR, unlike many other therapeutic combinations. We are hopeful this positive duration of response continues and, as seen in first line non-small cell lung cancer in the TACTI-002 trial evaluating efti in combination with KEYTRUDA, eventually contributes to an overall survival benefit for patients with first line head and neck cancer."

ESMO Congress 2024 Proffered Paper Oral Presentation
Title: Primary Results from TACTI-003: A Randomized Phase IIb Trial Comparing Eftilagimod Alpha (soluble LAG-3) Plus Pembrolizumab Versus Pembrolizumab Alone in First-Line Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma with CPS ≥1

Clinical Highlights from Randomised Cohort A in 1L HNSCC Patients with Any PD-L1 Expression (CPS ≥1)
Efti leads to higher Objective Response Rates (ORR)
• Efti in combination with pembrolizumab (E+P) led to a 32.8% ORR (34.5% including one partial response reported after data cut-off) in evaluable patients with CPS ≥1 (N=58) compared to 26.7% for pembrolizumab in evaluable patients with CPS ≥1 (N=60), according to RECIST 1.1. Imbalances of prognostic markers towards the pembrolizumab alone arm included HPV status, smoking status, and primary tumour location.

• E+P outperformance in patients with any PD-L1 expression was strongest in high PD-L1 expressing patients (CPS ≥20) with a 31.0% ORR (N=29) versus an 18.5% ORR for pembrolizumab alone (N=27), along with a complete response rate of 6.9% in E+P arm versus 3.7% for pembrolizumab alone. An additional partial response was reported in CPS ≥20 after data cut-off leading to a 34.5% ORR, a 1.9- fold increase in responses over pembrolizumab alone in this patient group.

Efti maintains a high Duration of Response (DOR)
• Durability of response was achieved with the addition of efti with a median DOR of 17.5 months s in the E+P arm (N=58) as compared to 17.1 months in the pembrolizumab alone arm (N=60)
o Data compares favourably to other anti-PD-1 combinations with cytotoxic drugs like chemotherapy or EGFR inhibitors, including a historical DOR of ~6 to ~7 months from antiPD-1 combined with chemotherapy in 1L HNSCC1-4

Efti increases Biological Activity
• A statistically significant increase in absolute lymphocyte count (ALC), measured as an exploratory biomarker, was seen in the E+P arm as shown in the graphic below, indicating an effective eftiinduced immune response in this randomised setting
ALC increase is in line with data from other Phase II trials evaluating efti in combination with chemotherapy in metastatic breast cancer or pembrolizumab in non-small cell lung cancer5-6

Efti continues to have favourable safety profile
• Efti in combination with pembrolizumab continues to have a favourable safety profile with no new safety signals observed
o Discontinuation rate from treatment emergent adverse events was similar for both E+P (4.3%) and for pembrolizumab alone (4.4%)
o Unlike other combinations with anti-PD-1 therapy, E+P continues to have a comparable safety profile to pembrolizumab alone other than injection site reactions as expected with efti’s subcutaneous delivery.

Additionally, E+P drives a high ORR and Disease Control Rate (DCR) in 1L HNSCC patients regardless of PD-L1 expression. In Cohorts A and B together (N=89), E+P achieved a 33.7% ORR (34.8% including one partial response reported after data cut-off) including 31 patients in Cohort B with negative PD-L1 (CPS <1). E+P also achieved a higher DCR compared to pembrolizumab monotherapy across all PD-L1 expression levels, with a consistent increase from 58.1% DCR in CPS <1, to 69.0% DCR in CPS 1-19, to 75.9% DCR in CPS ≥20.

This new data adds to the body of evidence that efti’s activation of antigen-presenting cells provides a strong boost to the immune system, enhancing the potential of immune checkpoint inhibitors (ICI) such as KEYTRUDA. As the only MHC Class II agonist in clinical development today, efti generates a broad anti-cancer immune response in combination with ICIs regardless of PD-L1 expression, including for patients with negative PD-L1 expression, in a unique and safe manner across multiple different cancers.

On September 15, 2024 Novomedison (CEO Young-il Koh and Myeong-se Lee), a new drug development company, reported on the 5th that it received approval from the Ministry of Food and Drug Safety for a phase 2 clinical trial of Poseltinib, a BTK/TEC inhibitor (Press release, NOBO Medicine, SEP 15, 2024, View Source;cat=12&nid=299064 [SID1234649254]).

Schedule your 30 min Free 1stOncology Demo!
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

                  Schedule Your 30 min Free Demo!

Poseltinib, currently under development by Novomedison, is a small molecule compound that Hanmi Pharmaceutical and Novomedison are jointly developing. The company explains that it is a substance that shows more potent activity against BTK, TEC, and BMX kinases than existing BTK inhibitors and has fewer side effects, so it can be effective in treating various malignant B-cell lymphomas.

This phase 2 clinical trial will evaluate the efficacy and safety of posseltinib in patients with relapsed and refractory central nervous system lymphoma, and will be conducted as a multi-institutional joint clinical trial at Seoul National University Hospital, Bundang Seoul National University Hospital, Samsung Seoul Hospital, Seoul Asan Medical Center, and Chonnam National University Hospital.

Meanwhile, Novomedison is also conducting an investigator-led multicenter Phase 2 clinical trial of posseltinib in relapsed and refractory diffuse large B-cell lymphoma, and announced interim results at ASCO (Free ASCO Whitepaper) (American Society of Clinical Oncology) this year. The trial has now completed patient recruitment, and efficacy and safety results are scheduled to be announced at ASH (Free ASH Whitepaper) (American Society of Hematology) in December.

On September 15, 2024 Scorpion Therapeutics, Inc. ("Scorpion"), a pioneering clinical-stage oncology company dedicated to transforming the lives of cancer patients by redefining the frontier of precision oncology, reported initial, first-in-human clinical results from its Phase 1/2 study of STX-478 in advanced solid tumor patients in a Proffered Paper late-breaking session at the European Society for Medical Oncology ("ESMO") Congress 2024 in Barcelona, Spain (Press release, Scorpion Therapeutics, SEP 15, 2024, View Source [SID1234646635]). Initial Phase 1 monotherapy data for STX-478, an oral, once-daily, mutant-selective, allosteric PI3Kα inhibitor, demonstrated potentially best-in-class PI3Kα inhibition, with anti-tumor activity observed in multiple cancer types, including HR+/HER2- breast cancer (BC), gynecological tumors, and other solid tumors. STX-478 was well-tolerated, including in pre-diabetic, diabetic and heavily pre-treated patients and showed no significant wild-type-mediated toxicities.

Schedule your 30 min Free 1stOncology Demo!
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

                  Schedule Your 30 min Free Demo!

"Approved and investigational non-selective PI3Kα inhibitors, as well as approved AKT inhibitors, have shown clinical benefit in HR+/HER2- breast cancer in Phase 3 studies. However, their therapeutic benefit is limited by PI3Kα pathway inhibition in normal tissues, resulting in dose-limiting toxicities, including hyperglycemia, rash and diarrhea"

"We are pleased to report the initial Phase 1/2 trial results of STX-478, which was designed as the first PI3Kα inhibitor to fully maximize the potential of pathway inhibition in patients with solid tumors and is the first program emerging from our next-generation precision oncology discovery engine," said Adam Friedman, M.D., Ph.D., Chief Executive Officer of Scorpion. "STX-478 demonstrates potent and potentially best-in-class PI3Kα pathway inhibition as established by our early, differentiated signals of monotherapy efficacy, which exceed benchmarks of other pathway inhibitors. We also are encouraged by early safety data that demonstrates minimal evidence of wild-type PI3Kα-mediated toxicities, with no patients discontinuing STX-478 due to treatment-related adverse events. Together, these results suggest that our highly-selective mutant PI3Kα inhibitor could overcome the limitations of currently available pathway inhibitors and, consequently, meaningfully improve clinical outcomes for patients with PI3Kα kinase or helical domain-mutated solid tumors. We look forward to continuing to progress our clinical-stage and discovery pipeline as we work to broaden the reach and impact of precision oncology for patients with high unmet medical need."

"Approved and investigational non-selective PI3Kα inhibitors, as well as approved AKT inhibitors, have shown clinical benefit in HR+/HER2- breast cancer in Phase 3 studies. However, their therapeutic benefit is limited by PI3Kα pathway inhibition in normal tissues, resulting in dose-limiting toxicities, including hyperglycemia, rash and diarrhea," said Alberto J. Montero, M.D., affiliated with University Hospitals Cleveland, and trial investigator. "By selectively targeting mutant PI3Kα, one of the most prevalent oncogenes in cancer, STX-478 has the potential to improve clinical outcomes and quality of life for patients during treatment. In the trial, STX-478 achieves exposures capable of driving several-fold deeper target inhibition than other PI3Kα inhibitors, while avoiding their toxicities, even with the majority of patients having prediabetes or diabetes. I am excited about the early results in patients with breast cancer and other solid tumors and look forward to further clinical development."

Initial Data from the Phase 1/2 Study of STX-478 in Advanced Solid Tumors

In the Proffered Paper presented at ESMO (Free ESMO Whitepaper), 61 patients with both kinase and helical domain PIK3CA mutations were treated with STX-478 at doses ranging from 20mg to 160mg daily, as of the data cutoff on June 21, 2024. Of the enrolled patients, 29 patients had HR+/HER2- BC and 32 patients had other solid tumors. Additionally, 54% of patients were pre-diabetic or diabetic, and 41% of BC patients had a prior PI3Kα pathway inhibitor. 97% of BC patients had previously received a CDK4/6 inhibitor. Enrolled patients were heavily pre-treated with a median of three prior lines of therapy (ranging from 1-7).

Pharmacokinetic and Selectivity Profile

Preliminary pharmacokinetic analysis supports once-daily dosing of STX-478, with dose proportional and linear STX-478 plasma exposure and an estimated half-life of approximately 60 hours. At doses ≥ 40mg QD, STX-478 exceeded the average exposures needed for in vivo efficacy in mouse models and achieved target coverage several fold higher than other approved or investigational PI3Kα inhibitors. STX-478 reached a maximum tolerated dose (MTD) of 100mg daily.

Preliminary Safety Data

STX-478 was well-tolerated in a high-risk population, which included diabetics, pre-diabetics and patients intolerant to other PI3Kα pathway inhibitors, populations excluded from other PI3Kα studies. Most treatment-related adverse events (TRAEs) were mild-to-moderate and transient; TRAEs of ≥ 15% included: fatigue (30%), hyperglycemia (23%), nausea (20%) and diarrhea (15%). No Grade ≥ 3 PI3Kα WT toxicity adverse events (hyperglycemia, diarrhea and rash) were observed, and minimal changes in fasting glucose were observed at any STX-478 dose level.

No patients discontinued STX-478 due to a TRAE, and two dose-limiting toxicities observed at 160mg rapidly resolved after a brief dose interruption.

Initial Clinical Activity Data

As of the data cutoff in 43 evaluable patients, the confirmed/unconfirmed overall response rate (ORR) was 23% (5/22) in HR+/HER2- metastatic breast cancer; 21% (9/43) in all tumor types; and 44% (4/9) in gynecologic cancers, which compares favorably to approved PI3Kα pathway inhibitors (monotherapy ORR 4 – 6%). All responses were confirmed following the data cutoff. The disease control rate across tumors was 67%. Tumor reductions were seen in 72% of all patients as a monotherapy agent across all dose levels. Multiple responses were seen in both PI3Kα kinase and helical domain mutant tumors at multiple dose levels, and many responses were sustained and deepened over several months of therapy.

Mutant PIK3CA circulating tumor DNA levels markedly decreased on therapy in 86% of patients (19/22 evaluable patients).

The presentation will be available here on Scorpion’s website following the conclusion of the session.

"Scorpion is dedicated to bringing highly-selective small molecules to cancer patients as quickly as possible, and the presentation of these data is a testament to the team’s exceptional execution and the productivity of our fully-integrated discovery organization," said Mark Chao, M.D., Ph.D., Chief Medical Officer of Scorpion. "These exciting data bolster our confidence in the profile of STX-478 and in the continued advancement of the trial as we actively enroll patients into ongoing multiple expansion cohorts across a range of solid tumors and in combinations with active standard of care agents including fulvestrant and CDK4/6 inhibitors in HR+/HER2- breast cancer and lay the groundwork for the rapid advancement of this novel treatment. We would like to thank the patients, caregivers and investigators for sharing our commitment to advancing next-generation cancer treatments, and we look forward to providing updates from this study at future medical meetings."

About STX-478

STX-478 was designed to improve outcomes in patients harboring PI3Kα mutations, one of the most prevalent drivers of cancer, occurring in over 166,000 patients per year with breast, gynecological and other solid tumors in the United States alone. In preclinical models, STX-478 demonstrated robust activity across a range of both kinase and helical domain PI3Kα mutations while sparing wild-type PI3Kα activity in normal tissues; previous generations of non-selective PI3Kα inhibitors have limited patient benefit due to these on-target toxicities. Scorpion’s Phase 1/2 clinical trial is a multi-center, global, open-label study designed to evaluate the safety and tolerability of STX-478 in multiple ascending doses for patients with locally advanced or metastatic HR+/HER2- breast cancer and other solid tumors driven by PI3Kα mutations. The program has rapidly advanced into multiple expansion cohorts across a range of solid tumors and in breast cancer as monotherapy and in combinations with fulvestrant and CDK4/6 inhibitors. To learn more about the first-in-human trial of STX-478, please visit this page.

On September 15, 2024 Johnson & Johnson reported additional results from the pivotal Phase 2b SunRISe-1 study, supporting the safety and efficacy profile of investigational TAR-200 for the treatment of patients with Bacillus Calmette-Guérin (BCG)-unresponsive, high-risk non-muscle-invasive bladder cancer (HR-NMIBC) (Press release, Johnson & Johnson, SEP 15, 2024, https://www.prnewswire.com/news-releases/new-data-from-tar-200-phase-2b-sunrise-1-study-show-84-percent-complete-response-rate-in-patients-with-high-risk-non-muscle-invasive-bladder-cancer-302248316.html [SID1234646632]). New data were featured in a late-breaking oral presentation at the European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) 2024 Congress (Abstract #LBA85).

Schedule your 30 min Free 1stOncology Demo!
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

                  Schedule Your 30 min Free Demo!

"The safety and efficacy profile observed across multiple patient cohorts in the SunRISe-1 study further supports the potential of TAR-200 for patients with high-risk non-muscle-invasive bladder cancer as an innovative targeted releasing system," said Michiel S. van der Heijden, M.D., Ph.D., medical oncologist at Netherlands Cancer Institute. "These results support the potential of this novel treatment approach for patients who are not responsive to BCG immunotherapy and who face life-altering options, such as radical cystectomy."

Pivotal Cohort 2 (TAR-200 monotherapy):
New results from all 85 patients enrolled in the pivotal cohort show a high, centrally-confirmed, single-agent complete response (CR) rate of 83.5 percent (95 percent confidence interval [CI], 74-91). Results show highly durable CRs without the need for reinduction, with 82 percent of patients maintaining response after a median follow-up of 9 months, and an estimated 12-month CR rate of 57.4 percent based on the Kaplan-Meier curve. The overall risk-benefit profile favors TAR-200 monotherapy (Cohort 2) in this patient population.[1] Earlier results from Cohort 2 were previously presented at the 2024 American Urological Association (AUA) Annual Meeting.

Cohorts 1 and 3 (TAR-200 plus cetrelimab [CET] and CET monotherapy, respectively):
First results from Cohort 1 showed a 67.9 percent centrally-confirmed CR (95 percent CI, 54-80; 28-66, respectively). The first results from Cohort 3 (CET monotherapy) showed a 46.4 percent centrally-confirmed CR. The overall risk-benefit profile favors TAR-200 monotherapy (Cohort 2) in this patient population. The CET monotherapy CR rate is numerically similar to previously published CR rates from this class of therapies.1

"Our mission, to stay in front of cancer, drives us to innovate in ways that truly redefine treatment paradigms for patients with bladder cancer," said Christopher Cutie, M.D., Vice President, Disease Area Leader, Bladder Cancer, Innovative Medicine, Johnson & Johnson. "The data from our SunRISe clinical program illuminate the possibility of an innovative approach in an outpatient setting with the potential to impact patient well-being and enhance the entire treatment experience."

Low discontinuation rates due to treatment-resistant adverse events (TRAEs) were seen with TAR-200 (Cohort 2, six percent) and CET (Cohort 3, seven percent) alone, with higher rates in the combination (Cohort 1, TAR-200 26 percent or CET 23 percent). The most common (>20 percent) TRAEs of any grade across Cohort 1 and 2 were pollakiuria, dysuria, hematuria and urinary tract infection. No treatment-related deaths were reported.1

About Bladder Cancer
Bladder cancer is the ninth most common cancer in the world.2 Although BCG immunotherapy has been accepted as the standard of care for nearly five decades, 30-40 percent of patients do not respond to BCG and experience disease recurrence or progression.3 In such scenarios, radical cystectomy (removal of the bladder and neighboring structures and organs) emerges as the primary treatment option. This major abdominal procedure requires a urinary diversion to be created to collect and store urine.4

About TAR-200
TAR-200 is an investigational targeted releasing system designed to provide extended local release of gemcitabine into the bladder. It is installed in a physician’s office setting during a 2-3 minute procedure with no anesthesia. In December 2023, the FDA granted TAR-200 Breakthrough Therapy Designation (BTD) for the potential future treatment of patients with BCG-unresponsive HR-NMIBC, who are ineligible for or elected not to undergo radical cystectomy (surgical removal of the bladder).

About SunRISe-1
SunRISe-1 (NCT04640623) is a randomized, parallel-assignment, open-label Phase 2 clinical study evaluating the safety and efficacy of TAR-200 in combination with cetrelimab, TAR-200 alone, or cetrelimab alone for BCG-unresponsive HR-NMIBC carcinoma in situ (CIS) patients who are ineligible for, or elected not to undergo, radical cystectomy. Participants are randomized to 1 of 4 cohorts: treatment with TAR-200 in combination with cetrelimab (Cohort 1), TAR-200 alone (Cohort 2), cetrelimab alone (Cohort 3), or TAR-200 alone for papillary disease only (Cohort 4). The primary endpoint for Cohorts 1-3 is CR rate at any time point. Secondary endpoints include duration of response, overall survival, pharmacokinetics, quality of life, safety, and tolerability. Cohorts 1 and 3 were closed to further enrollment effective June 1, 2023.

About TAR-200
TAR-200 is an investigational targeted releasing system, enabling extended release of gemcitabine into the bladder, increasing the amount of time the drug delivery system spends in the bladder and sustaining local drug exposure. The safety and efficacy of TAR-200 are being evaluated in Phase 2 and Phase 3 studies in patients with MIBC in SunRISe-2 and SunRISe-4, and NMIBC in SunRISe-1, SunRISe-3 and SunRISe-5.

About Cetrelimab
Cetrelimab is an investigational programmed cell death receptor-1 (PD-1) monoclonal antibody being studied for the treatment of bladder cancer, prostate cancer, melanoma, and multiple myeloma as part of a combination treatment. Cetrelimab is also being evaluated in multiple other combination regimens.

About High-Risk Non–Muscle-Invasive Bladder Cancer
High-risk non–muscle-invasive bladder cancer (HR-NMIBC) is a type of non-invasive bladder cancer that is more likely to recur or spread beyond the lining of the bladder, called the urothelium, and progress to invasive bladder cancer compared to low-risk NMIBC.5,6 HR-NMIBC makes up 15-44 percent of patients with NMIBC and is characterized by a high-grade, large tumor size, presence of multiple tumors, and CIS. Radical cystectomy is currently recommended for NMIBC patients who fail BCG therapy, with over 90% cancer-specific survival if performed before muscle-invasive progression.7,8 Given that NMIBC typically affects older patients, many may be unwilling or unfit to undergo radical cystectomy.9 The high rates of recurrence and progression can pose significant morbidity and distress for these patients.5,9

On September 15, 2024 Akeso reported the Phase 2 clinical results of its internally developed PD-1/VEGF bispecific antibody, ivonescimab, with or without ligufalimab (anti-CD47 antibody AK117) for the first-line treatment of PD-L1-positive (CPS≥1) recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) at the 2024 European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Conference (Press release, Akeso Biopharma, SEP 15, 2024, View Source [SID1234646631]).

Schedule your 30 min Free 1stOncology Demo!
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

                  Schedule Your 30 min Free Demo!

At the data cut-off date of March 19, 2024, results indicate that for HNSCC with a high need for rapid tumor reduction, the ivonescimab regimen has demonstrated clinically meaningful reduction in tumor size. When combined with ligufalimab, both tumor shrinkage and survival benefits demonstrated further improvement from ivonescimab alone. Both ivonescimab alone and the ivonescimab plus ligufalimab combination have achieved preliminary efficacy data that surpassed previously disclosed PD-1 studies.

The objective response rate (ORR) for ivonescimab monotherapy group is 30%, while the ORR increases to 60% in ivonescimab plus ligufalimab group. The disease control rate (DCR) is 80% for ivonescimab monotherapy group improves to 90% with ligufalimab. As of the report time, the antitumor efficacy of the ivonescimab continues to be promising, with some patients showing an improvement from stable disease (SD) to partial response (PR). The ORR for ivonescimab monotherapy and the combination of ivonescimab plus ligufalimab was to 40% and 65%, respectively.
The median progression-free survival (mPFS) for ivonescimab monotherapy group was 5.0 months, with the 6-month PFS rate not yet reached. For the combination with ligufalimab group, the mPFS was 7.1 months, with a 6-month PFS rate of 71.8%.
The safety profile of the ivonescimab for first-line treatment of PD-L1-positive R/M HNSCC was manageable, with no treatment-related adverse events (TRAE) leading to drug discontinuation or death in both the ivonescimab monotherapy and the ivonescimab plus ligufalimab groups.
Although programmed cell death protein 1 (PD-1) inhibitors combined with chemotherapy are approved as first-line treatments for recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC), some patients exhibit poor responses to this approach, highlighting the need for new treatment strategies. Akeso has initiated a phase 3 clinical study comparing ivonescimab combined with ligufalimab versus pembrolizumab for the first-line treatment of PD-L1 positive R/M HNSCC. This study offers the potential to provide a new, highly effective immunotherapy option for these patients and may pave the way for the advancement of cancer immunotherapy 2.0.