On May 23, 2024 Cogent Biosciences, Inc. (Nasdaq: COGT), a biotechnology company focused on developing precision therapies for genetically defined diseases, reported positive updated lead-in data from the company’s ongoing Phase 3 PEAK trial evaluating the selective and potent KIT mutant inhibitor, bezuclastinib, in combination with sunitinib, in patients with Gastrointestinal Stromal Tumors (GIST) (Press release, Cogent Biosciences, MAY 23, 2024, View Source [SID1234643621]). The data will be presented in a poster presentation at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in Chicago, IL on June 1. Cogent also announced today a new Phase 2 clinical trial of bezuclastinib plus sunitinib in later line GIST patients, sponsored by the Sarcoma Alliance for Research through Collaboration (SARC) and in collaboration with The Life Raft Group and Dana-Farber Cancer Institute.

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"These data presented today reinforce our excitement that the combination of bezuclastinib and sunitinib has the potential to become a new standard of care for advanced GIST patients," said Andrew Robbins, President and Chief Executive Officer at Cogent Biosciences. "Coupled with the impressive clinical activity demonstrated by the combination, the addition of bezuclastinib to sunitinib continues to be generally well-tolerated with an encouraging safety profile. We are pleased to report that the pace of enrollment in PEAK is significantly ahead of schedule, and we now expect enrollment to complete in the third quarter of 2024."

"We are also excited today to announce a collaboration with SARC, The Life Raft Group and Dana-Farber on a new Phase 2 clinical trial assessing the potential benefit of bezuclastinib with sunitinib in later line GIST patients who are not eligible for the PEAK study and currently have very limited treatment options," continued Mr. Robbins.

"There is tremendous need for additional treatment options for GIST patients," said Andrew Wagner M.D., Ph.D., Senior Physician, Center for Sarcoma and Bone Oncology, Dana-Farber Cancer Institute, and Associate Professor of Medicine, Harvard Medical School. "Today’s updated lead-in data from the bezuclastinib combination are very promising, and I remain excited about the ongoing PEAK trial. Additionally, with the announcement of this new study today, we have a clinical trial which allows us to explore the use of bezuclastinib with sunitinib in patients who are not eligible for the PEAK study."

PEAK Trial Update
PEAK is a randomized, open-label, global, Phase 3 clinical trial evaluating bezuclastinib in combination with sunitinib vs sunitinib alone in GIST patients previously treated with imatinib. In the updated lead-in data being presented at ASCO (Free ASCO Whitepaper), as of the cutoff date, April 1, 2024, the 42 patients in Part 1 have been on study for a median of 15.3 months. The median progression-free survival (mPFS) during treatment with bezuclastinib and sunitinib was 10.2 months in all patients. In a subset of second-line GIST patients with only prior imatinib, which most closely resembles patients currently enrolling in Part 2 of PEAK, the data demonstrate a mPFS of 19.4 months. In addition, the objective response rate (ORR) in all patients treated with bezuclastinib and sunitinib was 27.5% and in the subset of second-line patients the ORR was 33.3%, per investigator assessment. Combination treatment resulted in a disease control rate of 80% in all patients and 100% in patients with prior imatinib only.

Safety Data
As of the data cutoff, the combination of bezuclastinib and sunitinib does not appear to add to the severity of adverse events known to be associated with sunitinib monotherapy and is well-tolerated. The majority of treatment-emergent adverse events (TEAEs) were low-grade and reversible. No additional serious adverse reactions or discontinuations due to TEAEs have been reported since the last presentation of data in November 2023.

ASCO Poster Details
Title: Peak part 1 summary: A phase 3, randomized, open-label multicenter clinical study of bezuclastinib (CGT9486) and sunitinib combination versus sunitinib in patients with gastrointestinal stromal tumors (GIST)
Session Type and Title: Poster Session – Sarcoma
Session Date and Time: June 1, 2024, 1:30 PM-4:30 PM CDT

The poster will be available in the Posters and Publications portion of the Cogent website at approximately 8:00 AM ET on June 1.

Phase 2 SARC Trial
The open label, single arm Phase 2 trial sponsored by SARC and in collaboration with The Life Raft Group and Dana-Farber Cancer Institute is designed to evaluate the mPFS as well as the safety and tolerability of bezuclastinib plus sunitinib in 40 patients with GIST who have previously progressed on sunitinib. This trial will focus on later line patients, where limited treatment options are available. Additional details can be found on clinicaltrials.gov; Identifier NCT06208748. For more information about SARC or The Life Raft Group, please visit www.sarctrials.org or www.liferaftgroup.org.

Bezuclastinib Clinical Development
Enrollment continues in the Phase 3 registration-enabling PEAK study, which will include approximately 388 second-line, post imatinib GIST patients. Due to rapid enrollment, the Company now expects PEAK enrollment to be completed in the third quarter of 2024 with top-line results still expected by the end of 2025. Cogent remains on-track to complete enrollment in APEX in patients with advanced systemic mastocytosis (AdvSM) by the end of 2024 and report top-line results mid-2025 and complete enrollment in SUMMIT Part 2 in the second quarter of 2025 and report top-line results by the end of 2025.

Upcoming Investor Conference
Cogent will participate in the Jefferies Global Healthcare Conference on Wednesday, June 5 at 2:30 p.m. ET. A live webcast will be available on the Investors & Media page of Cogent’s website at investors.cogentbio.com/events. A replay will be available approximately two hours after completion of the event and will be archived for up to 30 days.

On May 23, 2024 Aulos Bioscience, an immuno-oncology company working to revolutionize cancer care through the development of best-in-class IL-2 therapeutics, reported interim results from its Phase 1/2 trial of AU-007, the first human monoclonal antibody designed using artificial intelligence to be tested in a clinical trial (Press release, Aulos Bioscience, MAY 23, 2024, View Source [SID1234643620]). The data will be presented in a poster session at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2024 Annual Meeting in Chicago, Illinois.

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"The level and scope of anti-tumor activity we’re seeing across solid tumor types are remarkable so early in clinical development, particularly the partial responses and metabolic complete response. The durability of the tumor reductions seen in several patients suggests the formation of immune memory of the cancerous cells. These results validate our long-held belief that AU-007 could widen the therapeutic window of IL-2 by redirecting IL-2 toward CD8+ T and natural killer cells that can kill tumor cells and away from immunosuppressive regulatory T cells and the vasculature," said Aron Knickerbocker, Aulos Bioscience’s chief executive officer. "While other developmental IL-2 therapies focus on changing IL-2 itself, AU-007 is a human antibody that is a well-established therapeutic modality. This provides sources of advantage and differentiation. As we treat patients in earlier lines of therapy, we are confident AU-007 is emerging as a potential best-in-class regimen."

Key findings from the updated results of the AU-007 Phase 1/ 2 study, with data available on 59 patients as of the data cutoff date of April 9, 2024, are as follows.

Well-tolerated safety profile:

No evidence of vascular leak syndrome or pulmonary edema reported at all dose levels evaluated.
All drug-related adverse events were Grade 1 or 2 except for:
One patient with Grade 4 CRS that resolved quickly with steroids. This patient was noted retrospectively to have subclinical elevated IL-6 serum levels at baseline.
Five patients experienced transient (3-7 days) Grade 3 or 4 lymphopenias that were not associated with adverse outcomes. Transient lymphopenia is a known effect of IL-2 treatment as lymphocytes traffic out of blood and into tissue.
One patient with Grade 3 anemia who entered the study with Grade 2 anemia.
Profound and durable tumor shrinkage observed in multiple tumor types:

A patient with large-volume metastatic melanoma whose tumors had progressed through anti-PD-1 and anti-CTLA-4 checkpoint inhibitors was treated with AU-007 (9 mg/kg) and one 135K IU/kg low dose of IL-2 and experienced 76% shrinkage (unconfirmed partial response) in target lesions at 8 weeks.
Another patient with metastatic melanoma whose tumors had also progressed through anti-PD-1 and anti-CTLA-4 checkpoint inhibitors was treated with AU-007 (4.5 mg/kg) and one 15K IU/kg low dose of IL-2 and achieved 48% shrinkage in target lesions.
A patient with head and neck cancer whose tumors had progressed through an anti-PD-1 checkpoint inhibitor was treated with AU-007 (4.5 mg/kg) and 45K IU/kg IL-2 dose every two weeks and experienced 32% shrinkage (confirmed partial response) in a cervical bone metastasis, as well as reduced pain and improved motor function in an affected hand.
A patient with bladder cancer whose tumors had progressed through an anti-PD-L1 checkpoint inhibitor was treated with AU-007 (4.5 mg/kg) and one 45K IU/kg IL-2 dose and achieved a durable metabolic complete response.
Additional tumor shrinkages were observed in patients with widespread large-volume disease in renal cell carcinoma (RCC), non-small cell lung cancer (NSCLC) and MSI-stable (MSS) colorectal cancer.
Unique pharmacodynamic (PD) and pharmacokinetic (PK) profiles in the IL-2 class:

Decreases in peripheral regulatory T cells (Tregs) and increases in CD8/Treg ratios demonstrate AU-007’s ability to redirect IL-2 and prevent the negative feedback loop to Tregs. AU-007 and low-dose aldesleukin also substantially increases peripheral natural killer (NK) cells.
AU-007 PK demonstrates dose-proportionality over the dose range tested and no signs of neutralizing anti-drug antibodies (ADAs) activity, and a half life of 15+ days.
The Phase 2 expansion cohorts of the AU-007 study are continuing to enroll patients with a focus on melanoma and RCC. The company anticipates presenting updated clinical data in the second half of 2024. Additional Phase 2 expansion cohorts are planned to evaluate AU-007 and aldesleukin in second-line PD-L1+ NSCLC, with and without the PD-L1 antibody avelumab.

The poster, "Updated results of a phase 1/2 study of AU-007, a monoclonal antibody (mAb) that binds to IL-2 and inhibits CD25 binding, in patients with advanced solid tumors," (Abstract 2527) is available to meeting registrants as an electronic poster on the ASCO (Free ASCO Whitepaper) online meeting platform and will be presented live in the poster session "Developmental Therapeutics—Immunotherapy" on Saturday, June 1, 2024, 9:00 a.m. to 12:00 p.m. CDT.

To learn more about the AU-007 clinical trial program, please visit ClinicalTrials.gov (identifier: NCT05267626). For patients and providers in the U.S., please visit www.solidtumorstudy.com. For patients and health professionals in Australia, please visit www.solidtumourstudy.com.

About AU-007
AU-007 is a human IgG1 monoclonal antibody designed using artificial intelligence that is highly selective to the CD25-binding portion of IL-2. With a mechanism of action unlike any other IL-2 therapeutic in development, AU-007 leverages IL-2 to reinforce anti-tumor immune effects. This is achieved by preventing IL-2, either exogenous or secreted by effector T cells, from binding to trimeric receptors on regulatory T cells while still allowing IL-2 to bind and expand effector T cells and NK cells. This prevents the negative feedback loop caused by other IL-2-based treatments and biases the immune system toward activation over suppression. AU-007 also prevents IL-2 from binding to CD25-containing receptors on eosinophils, as well as vasculature and pulmonary endothelium, which may significantly reduce the vascular leak syndrome and pulmonary edema associated with high-dose IL-2 therapy.

On May 23, 2024 Affimed N.V. (Nasdaq: AFMD), a clinical-stage immuno-oncology company committed to giving patients back their innate ability to fight cancer, reported that an update from the Company’s AFM24-102 study in advanced EGFR wild-type (EGFRwt) non-small cell lung cancer (NSCLC) will be presented at the annual meeting of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) to be held in Chicago on May 31 – June 4, 2024 (Press release, Affimed, MAY 23, 2024, View Source [SID1234643619]). Patients in the study are treated with the combination of AFM24, Affimed’s innate cell engager (ICE), and atezolizumab, Roche’s checkpoint inhibitor (CPI).

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As of the March 18 cut-off for the poster, 17 patients with EGFRwt NSCLC received the combination treatment and 15 patients were response evaluable. One patient showed a confirmed complete response, and three patients showed confirmed partial responses (PR). In addition, seven patients achieved stable disease, resulting in a disease control rate of 73.3% (11/15 patients). Median progression-free survival was 5.9 months.

All responders were resistant to checkpoint inhibitor treatment prior to the study, which supports the hypothesis that combining AFM24 with atezolizumab may enhance the cancer-immunity cycle and provide an alternative strategy to overcome resistance to existing therapies for EGFR-expressing tumors.

AFM24 and atezolizumab were given at their respective single agent doses. Treatment in these heavily pretreated patients was well tolerated. Side effects were consistent with the known safety profiles of these agents. The most frequent side effects observed were mild to moderate infusion related reactions and transient mild to moderate increase in liver enzymes.

"We are very encouraged to see objective and lasting responses in patients who have failed multiple lines of therapy including platinum doublets and checkpoint inhibitors," said Dr. Andreas Harstrick, Chief Medical and acting Chief Executive Officer of Affimed. "These data support our hypothesis that the combination of AFM24 and PD-1 targeting may act synergistically on the immunity cycle. It is remarkable that this can be achieved with a chemotherapy-free approach. We are committed to continuing clinical development of this therapy and are enrolling additional patients for both EGFRwt and EGFRmut NSCLC."

The EGFRwt NSCLC cohort of the study will enroll up to 40 patients and the EGFRmut NSCLC cohort will enroll up to 25 patients.

The full data set will be presented by Dr. Hye Ryun Kim, Professor at Yonsei University College of Medicine, Seoul, Korea, at ASCO (Free ASCO Whitepaper) on June 1, 2024, during the poster session on Developmental Therapeutics—Immunotherapy (9:00 a.m.—12:00 p.m. CDT).

The abstract and more details about the ASCO (Free ASCO Whitepaper) conference are available online at Attend | ASCO (Free ASCO Whitepaper) Annual Meeting. The poster will be available online at View Source the presentation.

Conference Call and Webcast Information

Affimed will host a conference call and webcast for the financial community on June 1, 2024, at 6:00 p.m. CDT / 7:00 p.m. EDT.

The conference call will be available via phone and webcast. The live audio webcast of the call will be available in the "Webcasts" section on the "Investors" page of the Affimed website at View Source To access the call by phone, please use link:

https://register.vevent.com/register/BIff607338e5d247f99b548240be2ad413, and you will be provided with dial-in details and a pin number.

About AFM24

AFM24 is a tetravalent, bispecific ICE that activates the innate immune system by binding to CD16A on innate immune cells and epidermal growth factor receptors (EGFR), a protein widely expressed on solid tumors, to kill cancer cells. Generated by Affimed’s fit-for-purpose ROCK platform, AFM24 represents a distinctive mechanism of action that uses EGFR as a docking site to engage innate immune cells for tumor cell killing through antibody-dependent cellular cytotoxicity and antibody-dependent cellular phagocytosis.

On May 23, 2024 Theratechnologies Inc. ("Theratechnologies" or the "Company") (TSX: TH) (NASDAQ: THTX), a biopharmaceutical company focused on the development and commercialization of innovative therapies, reported Phase 1 data demonstrating signs of long-term efficacy and a manageable safety profile of its lead investigational peptide drug conjugate (PDC) candidate, sudocetaxel zendusortide (TH1902), in patients with solid tumors (Press release, Theratechnologies, MAY 23, 2024, View Source [SID1234643618]). The data will be presented in a poster session on June 1, 9:00 AM-12:00 PM CDT (abstract #3081, poster board #226) at the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) annual meeting, which is taking place May 31-June 4, 2024, in Chicago, IL.

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In an updated analysis from Parts 1 and 2 of an ongoing Phase 1 clinical trial, sudocetaxel zendusortide induced durable disease stabilization (up to 45 weeks) lasting beyond treatment completion. The results suggest a unique, multimodal mechanism of action distinct from other cancer therapeutics, including induction of immune cell infiltration even in "cold" tumor models, inhibition of vasculogenic mimicry, targeting of chemotherapy-resistant cancer stem cells, and activation of the cGAS/STING immune pathway, among other actions. Additionally, investigators observed an early efficacy signal primarily in female cancers (ovarian cancer, endometrial cancer, triple-negative breast cancer [TNBC]), with seven of 16 participants (44%) achieving a clinical benefit rate (complete response + partial response + stable disease), as confirmed via Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. The poster presentation, which constitutes the first report of long-term efficacy, safety, and pharmacokinetic (PK) data from the Phase 1 study, also suggests that sudocetaxel zendusortide has a manageable safety profile when dosed at 300mg/m2, with few Grade 3 adverse events (AEs).

"The initial long-term Phase 1 data further validate and expand upon the preliminary evidence of antitumor activity with sudocetaxel zendusortide in individuals with solid tumors," said Ira Winer, M.D., Ph.D., FACOG, a member of the Gynecologic Oncology and Phase 1 Clinical Trials Multidisciplinary Teams at Karmanos Cancer Center and Associate Professor of Oncology at Wayne State University. "It is highly unusual to see such long-lasting disease stabilization even after treatment cessation in patients with advanced disease. These updated data provide an informative baseline as we seek to optimize the dose of this novel peptide-drug conjugate in patients with platinum-resistant ovarian cancer in the next stage of the Phase 1 trial."

Study details

Dr. Winer and colleagues conducted an analysis of the long-term efficacy, safety, and PK of sudocetaxel zendusortide from Parts 1 and 2 of the Phase 1 trial, which seeks primarily to characterize the agent’s safety and tolerability. Part 1 (modified intrapatient dose escalation, n=18) included patients with recurrent/refractory advanced tumors (all comers) with no limit on the number of previous therapies, including taxanes. Part 2 (dose expansion, n=18) included patients with cancers with known high expression of the sortilin (SORT1) receptor, including ovarian cancer, endometrial cancer, TNBC, and melanoma. Part 3 (dose optimization) of the Phase 1 trial, in patients with advanced ovarian cancer that is no longer platinum-sensitive, is ongoing.

In a sub-analysis of efficacy in 16 patients with TNBC, ovarian, and endometrial cancers, seven patients exhibited RECIST 1.1-confirmed clinical benefit, with six patients achieving long-term stabilization of disease (up to a maximum of 45 weeks in duration) even after drug discontinuation in some patients. One patient with ovarian cancer had an overall partial response (PR), with a RECIST 1.1-confirmed complete response (CR) in target lesions, and stabilization of disease (SD) in non- target lesions, lasting up to 24 weeks from initiation of treatment. In addition, one patient with endometrial cancer, whose dose was escalated from 60 mg/m2 to 360 mg/m2 in Part 1, completed a total of 11 treatment cycles; this patient’s disease remained stable throughout eight months of treatment, up to the time of consent withdrawal. All 16 patients had prior exposure to taxane-containing regimens (range: 1-6). The investigators characterized the prolonged stabilization of disease as clinically significant in this heavily pretreated patient population, which typically experiences recurrence during or shortly after treatment discontinuation.

Sudocetaxel zendusortide has a manageable safety profile, with most treatment-related AEs rated as mild to moderate in severity and managed with standard supportive care or dose reductions. Investigators noted that the low number of Grade 3 AEs compares favorably to the published literature for unconjugated docetaxel.

PK measures showed that exposure to free docetaxel was much lower than that for sudocetaxel zendusortide, a finding that may explain the lower incidence and severity of AEs seen with sudocetaxel zendusortide versus docetaxel alone. The maximum concentration (Cmax) of sudocetaxel zendusortide was 30.4 micromolar (μM), compared to 0.58 μM for free docetaxel. The 24-hour area under the curve (AUC24) for sudocetaxel zendusortide was 74.8 nanomoles per hour per liter (h.nmol/mL), versus 3.1 h.nmol/mL for free docetaxel. The free docetaxel/sudocetaxel zendusortide AUC ratio was less than 1% up to 300 mg/m2, suggesting that most docetaxel remains associated with the peptide over the period of analysis.

"One year after our presentation of preliminary evidence of antitumor activity at the 2023 ASCO (Free ASCO Whitepaper) annual meeting, the Phase 1 sudocetaxel zendusortide trial continues to yield important information about long-term efficacy, safety, and pharmacokinetics of this promising peptide-drug conjugate," commented Christian Marsolais, Ph.D., Senior Vice President and Chief Medical Officer at Theratechnologies. "These latest data leave us well positioned for Part 3 of the study, in which we aim to optimize the dose to see further signs of efficacy while limiting toxicity. We look forward to sharing more data from this ongoing trial in the future."

About Sudocetaxel Zendusortide (TH1902) and SORT1+ Technology

Sudocetaxel zendusortide is a first-of-its-kind sortilin receptor (SORT1)-targeting PDC, and the first compound to emerge from the Company’s broader licensed oncology platform. A new chemical entity, sudocetaxel zendusortide employs a cleavable linker to conjugate (attach) a proprietary peptide to docetaxel, a well-established cytotoxic chemotherapeutic agent used to treat many cancers. The FDA granted Fast Track designation to sudocetaxel zendusortide as a single agent for the treatment of all sortilin-positive recurrent advanced solid tumors that are refractory to standard therapy. Sudocetaxel zendusortide is currently being evaluated in a Phase 1 clinical trial.

Theratechnologies has established the SORT1+ Technology platform as an engine for the development of PDCs that target SORT1, which is expressed in multiple tumor types. SORT1 is a "scavenger" receptor that plays a significant role in protein internalization, sorting, and trafficking. Expression of SORT1 is associated with aggressive disease, poor prognosis, and decreased survival. It is estimated that SORT1 is expressed in 40% to 90% of endometrial, ovarian, colorectal, triple-negative breast (TNBC), and pancreatic cancers, making this receptor an attractive target for anticancer drug development.

On May 23, 2024 Sensei Biotherapeutics, Inc. (Nasdaq: SNSE), a clinical stage immuno-oncology company focused on the discovery and development of next-generation therapeutics for cancer patients, reported encouraging clinical data from the dose escalation portion of its Phase 1/2 trial of SNS-101, a conditionally active, human monoclonal antibody targeting the immune checkpoint VISTA (V-domain Ig suppressor of T cell activation) (Press release, Sensei Biotherapeutics, MAY 23, 2024, View Source [SID1234643617]).

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"I am pleased that SNS-101 has been well-tolerated in the study, reaching its highest planned dose level with no dose limiting toxicities and demonstrating its potential to successfully overcome the prior challenges of VISTA-targeted programs," said Dr. Shiraj Sen, Medical Oncologist and Director of Clinical Research at NEXT Oncology, Dallas, and a principal investigator for the SNS-101 study. "The data show encouraging signs of clinical activity in a heterogeneous population of patients with advanced solid tumors, where you typically wouldn’t expect to see clinical responses, especially in microsatellite stable colorectal and endometrial tumors. There is a continued unmet need for patient populations that have become resistant or don’t respond to current immunotherapy treatment options. I look forward to continuing to evaluate its progress."

Dose escalation portion of the Phase 1/2 clinical trial

The dose escalation portion of the Phase 1/2 clinical trial is designed to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and efficacy of SNS-101. This study assesses SNS-101 both as monotherapy and in combination with Regeneron’s PD-1 inhibitor Libtayo (cemiplimab, 350 mg), in patients with advanced solid tumors with primary (unfavorable candidates for immunotherapy) or acquired PD-1 therapy resistance (progressed on prior anti-PD-1 therapy).

A total of 34 patients received SNS-101 once every 3 weeks, with 16 patients in the monotherapy arm and 18 patients in the combination arm. The majority of patients (85%) had a tumor type that is typically unresponsive to PD-1 monotherapy ("cold" tumors).

As of the April 30, 2024 data cutoff, SNS-101 demonstrated preliminary evidence of promising clinical activity in multiple tumor types, including:

One microsatellite stable (MSS) endometrial cancer patient that received SNS-101 plus cemiplimab had a confirmed partial response (59% decrease) and remains on study at 30+ weeks. MSS endometrial cancer has been previously shown to have a low response rate to monotherapy immunotherapy treatments.
One MSS colorectal cancer (CRC) patient that received SNS-101 plus cemiplimab remained on study for 18 weeks and had tumor regression of 27%. MSS CRC has been previously shown to be unresponsive to PD-1 treatments.
One pembrolizumab-resistant renal cell carcinoma patient that received SNS-101 plus cemiplimab remained on study for 12 weeks and had tumor regression of 18%.
One pembrolizumab-resistant human papillomavirus (HPV)+ head and neck cancer patient that received SNS-101 as monotherapy remained on study for 12 weeks and had tumor regression of 17%.
These clinical data are consistent with preclinical studies suggesting therapeutically relevant clinical doses of SNS-101 at 3mg/kg or higher. Additionally, preliminary flow-based pharmacodynamic analysis showed dose-dependent changes in specific T-cell populations suggesting SNS-101 may be having a pharmacological effect on T-cell subsets.

SNS-101 demonstrated a potentially best-in-class pharmacokinetic (PK) profile with linear elimination kinetics and dose-proportional increases in exposure, supporting once every three week dosing. The data are consistent with lack of target-mediated drug disposition (TMDD), which has been observed in non-conditionally active anti-VISTA antibodies.

SNS-101 was well tolerated alone and in combination with cemiplimab, with no dose-limiting toxicities observed. The majority of AEs were Grade 1 or 2 in severity. Two patients experienced Grade 1 cytokine release syndrome (CRS), one in monotherapy and one in combination, both at the highest dose of SNS-101. Both cases were mild and manageable, demonstrating that SNS-101 has the potential to overcome a key hurdle that hindered first-generation VISTA-targeting approaches. Four patients in the combination cohort experienced immune-mediated events. There were also no significant changes to key inflammatory cytokine levels, including interferon gamma, interleukin-6, interleukin-10, interleukin-8, TNF-alpha, and CCL5-RANTES, across cohorts.

"The dose escalation portion of the Phase 1/2 trial of SNS-101 answers the critical question of whether a pH-selective approach can overcome the previous hurdles associated with targeting VISTA, which included severe safety and PK issues. We believe the topline data presented today marks an important milestone and validates the mechanism of action by demonstrating the potentially best-in-class PK and a well-tolerated safety profile of SNS-101 at therapeutically relevant dose levels," said Ron Weitzman, Chief Medical Officer of Sensei Bio. "We saw promising clinical activity primarily in tumor types that don’t typically respond to PD-1 monotherapy and look forward to progressing through the expansion phase of the study."

Ongoing dose expansion portion of the Phase 1/2 clinical trial

Patient enrollment is advancing in the dose expansion portion of the Phase 1/2 study. The Company expects to report initial data from the dose expansion cohorts and to hold an end-of-Phase 1 meeting with the FDA by the end of 2024.

ASCO presentation

The data will be presented in a poster presentation entitled "Initial results from a first-in-human phase 1 study of SNS-101 (pH-selective anti-VISTA antibody) alone or in combination with cemiplimab in patients with advanced solid tumors," on June 1, 2024, at the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting being held in Chicago, IL. The poster will be available on the Sensei website at the start of the poster presentation.

Investor webcast

Sensei will host a webcast on Monday, June 3, 2024, at 8:00 a.m. ET (7:00 a.m. CT) to discuss the data. Participating alongside Company management will be Dr. Shiraj Sen, M.D., Ph.D., Medical Oncologist and Director of Clinical Research at NEXT Oncology-Dallas. Dr. Sen is an investigator on the ongoing Phase 1/2 clinical trial for SNS-101, and lead author of the SNS-101 poster. The live event can be accessed here: View Source and can be accessed on the Investor page of Sensei’s website at View Source A replay of the webcast will be available after the completion of the event.