On May 26, 2022 Elevation Oncology, Inc. (Nasdaq: ELEV), a clinical stage biopharmaceutical company focused on the development of precision medicines for patients with genomically defined cancers, reported positive initial clinical proof-of-concept data from its ongoing Phase 2 CRESTONE study evaluating the safety and efficacy of seribantumab in patients with advanced solid tumors that harbor NRG1 gene fusions (Press release, Elevation Oncology, MAY 26, 2022, View Source;utm_medium=rss&utm_campaign=elevation-oncology-to-present-initial-seribantumab-proof-of-concept-data-from-phase-2-crestone-study-in-patients-with-tumors-harboring-nrg1-fusions-at-asco-2022 [SID1234615077]). These data will be presented at the 2022 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, being held in Chicago from June 3-7, 2022.

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"The response rate observed in the Cohort 1 patient population, including complete and partial responses, together with early signs of durable responses and a well-tolerated safety profile, demonstrate the potential of seribantumab to become a best-in-class therapy with a differentiated profile for patients whose tumor harbors an NRG1 fusion," said Valerie Malyvanh Jansen, MD, PhD, Chief Medical Officer of Elevation Oncology. "These initial results further support our confidence in the tumor-agnostic clinical development strategy for seribantumab and targeting genomically defined patient populations. We look forward to continuing to advance seribantumab to address the significant unmet needs of patients with NRG1 fusions."

"NRG1 fusions have been identified in a variety of solid tumors, including lung, pancreatic, gallbladder, breast, ovarian and colorectal cancers, among others, and patients with these tumors typically have a poor prognosis and limited response to available therapies," said Daniel Carrizosa, MD, Medical Oncologist at Atrium Health Levine Cancer Institute, and an investigator for the CRESTONE study. "These initial results, including the 33% response rate and disease control rate of greater than 90%, demonstrate clear, clinical proof-of-concept for seribantumab monotherapy, and support the potential opportunity to provide patients with a meaningful new treatment option. We look forward to sharing the data with the medical and scientific community at ASCO (Free ASCO Whitepaper) in June."

The efficacy data being presented are from 12 patients evaluable for investigator-assessed response per RECIST v1.1. All patients were treated with seribantumab monotherapy dosed at 3g weekly IV, in Cohort 1 of CRESTONE, which includes patients with no prior pan-ERBB, HER2 or HER3 targeted therapy, with centrally confirmed NRG1 gene fusion status via RNA-based next generation sequencing assay.

Key Findings from CRESTONE as of the data cut-off date of April 18, 2022

Enrollment consisted of 15 patients in Cohort 1 with non-small cell lung cancer (NSCLC) (n=14) or pancreatic cancer (n=1) whose tumors harbor an NRG1 fusion
12 patients were evaluable for response per RECIST v1.1, with a median age of 61 years (range 44-76), and a median of 1 line of prior systemic therapy (range 1-5)
Across all tumor types (n=12), the investigator-assessed objective response rate (INV-ORR) was 33%, including two complete responses (CRs; 17%) and two partial responses (PRs; 17%)
Disease control rate was 92%
Durations of response range from 1.4 – 11.5 months
75% of responding patients remain on treatment
In NSCLC (n=11), the INV-ORR was 36%, including two CRs (18%) and two PRs (18%)
Seribantumab demonstrated a favorable and tolerable safety profile across the 35 patients evaluable for safety, which was comprised of patients from Cohorts 1, 2 and 3, along with patients from the safety run-in portion of the study
Majority (80%) of adverse events (AEs) were mild or moderate (Grade 1 or 2) in severity
There were two Grade 3 treatment-related AEs (TRAEs), diarrhea (n=1) and vomiting (n=1), and no Grade 4 or 5 TRAEs
No patients discontinued seribantumab due to AEs
2 patients (6%) received dose reductions for AEs
77% of patients (27 of 35) received the optimized recommended Phase 2 dose of seribantumab (3g QW)
"We are pleased to be reporting these first-ever CRESTONE data of seribantumab in patients whose tumors harbor NRG1 gene fusions, and we remain on track to complete enrollment of the first 20 patients in Cohort 1 in mid-2022," said Shawn M. Leland, PharmD, RPh, Founder and Chief Executive Officer of Elevation Oncology. "We believe these initial data support the continued evaluation of seribantumab, and its potential ability to address the underlying drivers of tumor growth for this difficult-to-treat genomic alteration. We look forward to reporting additional data from CRESTONE in the first half of 2023."

Seribantumab was recently granted Fast Track designation by the U.S. Food and Drug Administration for the tumor-agnostic treatment of advanced solid tumors that harbor NRG1 gene fusions.

The full presentation can be accessed on the Elevation Oncology website at elevationoncology.com/resources/publications/ following completion of the live presentation at ASCO (Free ASCO Whitepaper).

Expected Upcoming Milestones

Complete enrollment of the first 20 patients in Cohort 1 of the CRESTONE study in mid-2022
Additional interim data from the CRESTONE Phase 2 study are expected in the first half of 2023
Topline data from the CRESTONE Phase 2 study results are expected in 2024
Ongoing target evaluation and continued execution of Elevation Oncology’s strategy for future pipeline expansion
Conference Call and Webcast Information

The Company will host an investor conference call and webcast today, Thursday, May 26, 2022, at 6:00pm ET to discuss the Phase 2 CRESTONE data. Elevation Oncology’s management team will be joined by Daniel R. Carrizosa, MD, a recognized thought leader in oncology and NRG1 fusions, and a principal investigator of the CRESTONE study. To access the live call, please dial 1-877-870-4263 (local) or 1-412-317-0790 (international) at least 10 minutes prior to the start time of the call and ask to be joined into the Elevation Oncology call. The live, listen-only webcast of the conference call can be accessed by visiting the "Events" page within the "Investors" section of the Company’s website at www.elevationoncology.com. An archived replay of the webcast will be available on the Company’s website approximately two hours after the event.

Details for the ASCO (Free ASCO Whitepaper) 2022 oral presentation are as follows:

Title: CRESTONE: Initial efficacy and safety of seribantumab in solid tumors harboring NRG1 fusions
First Author: Daniel R. Carrizosa, Atrium Health Levine Cancer Institute
Abstract Number: 3006
Session: Developmental Therapeutics – Molecularly Targeted Agents and Tumor Biology
Date and Time: Tuesday, June 7, 2022, 11:45AM-11:57AM CT

About the Phase 2 CRESTONE Study

CRESTONE (Clinical Study of Response to Seribantumab in Tumors with Neuregulin-1 (NRG1) Fusions; NCT04383210) is a Phase 2 tumor-agnostic, three-cohort study evaluating seribantumab in patients with solid tumors that harbor an NRG1 fusion and have progressed after at least one prior line of standard therapy. The primary objective of the study is to describe the anti-tumor activity and safety of seribantumab as a monotherapy specifically in patients whose solid tumor is uniquely driven by an NRG1 gene fusion. CRESTONE offers a clinical trial opportunity for patients with advanced solid tumors who have not responded or are no longer responding to treatment. Patients are encouraged to talk to their doctor about genomic testing of their tumor. CRESTONE is open and enrolling today in the United States, Australia, and Canada. For more information visit www.NRG1fusion.com.

About Seribantumab and NRG1 Gene Fusions

Seribantumab is a fully human IgG2 monoclonal antibody that binds to human epidermal growth factor receptor 3 (HER3). HER3 is traditionally activated through binding of its primary ligand, neuregulin-1 (NRG1). The NRG1 gene fusion is a rare genomic alteration that combines NRG1 with another partner protein to create chimeric NRG1 "fusion proteins". The NRG1 fusion protein is often also able to activate the HER3 pathway, leading to unregulated cell growth and proliferation. Importantly, NRG1 gene fusions are predominantly mutually exclusive with other known genomic driver mutations and are considered a unique oncogenic driver event associated with tumor-cell survival.

NRG1 fusions have been identified in a variety of solid tumors, including lung, pancreatic, gallbladder, breast, ovarian, colorectal, neuroendocrine, cholangiocarcinomas, and sarcomas. In preclinical experiments, seribantumab prevented the activation of HER3 signaling in cells that harbor an NRG1 gene fusion and destabilized the entire ERBB family signaling pathway including the activation of HER2, EGFR, and HER4. In addition to extensive nonclinical characterization and testing, seribantumab has been administered to more than 800 patients across twelve Phase 1 and 2 studies, both as a monotherapy and in combination with various anti-cancer therapies. Seribantumab was granted Fast Track designation by the FDA for the tumor-agnostic treatment of patients whose solid tumors harbor NRG1 fusions and is currently being evaluated in the Phase 2 CRESTONE study for patients with solid tumors of any origin that harbor an NRG1 fusion.

On May 26, 2022 Mirati Therapeutics, Inc. (NASDAQ: MRTX), a clinical-stage targeted oncology company, reported positive results from the registration-enabling Phase 2 cohort of the KRYSTAL-1 study evaluating adagrasib 600 mg BID in patients with non-small cell lung cancer (NSCLC) harboring the KRASG12C mutation who have received at least one prior systemic therapy (Press release, Mirati, MAY 26, 2022, View Source [SID1234615094]). Findings will be presented on June 3 at the 2022 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, as an oral presentation during the "Lung Cancer – Non-Small Cell Metastatic" session from 2:24 to 2:36 PM ET/ 1:24 to 1:36 PM CT (Abstract #9002).

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Summary of Clinical Results from Phase 2 Registration-Enabling Study
As of October 15, 2021, 116 patients were enrolled and treated in the study. Of the patients enrolled, 98% had prior treatment with a PD-1/L1 inhibitor following or in combination with chemotherapy. Median follow up was 12.9 months.
Of the patients evaluable for response (n=112), initial results showed that the objective response rate (ORR) by Blinded Independent Central Review (BICR) was 43%, the disease control rate (DCR) was 80%, the median duration of response (DOR) was 8.5 months (95% confidence interval [CI]: 6.2 – 13.8), and the median progression-free survival (PFS) was 6.5 months (95% CI: 4.7 – 8.4).
With a January 15, 2022 data cutoff, the median overall survival (OS) was 12.6 months (95% CI: 9.2 – 19.2).
The safety profile of adagrasib in this study was consistent with prior reports and no new safety signals were observed. The most frequent treatment related adverse events (TRAEs) included gastrointestinal events and fatigue. The majority of TRAEs were Grade 1–2 (53%) with Grade 3–4 TRAEs observed in 43% of patients. Two Grade 5 TRAEs were observed. TRAEs led to discontinuation of therapy in only 7% of patients.
"The positive and encouraging data from this trial further support the scientific rationale for targeting the KRASG12C mutation with adagrasib, which fully and continually inhibits mutant KRASG12C throughout the entire dosing period," says Alexander I. Spira, M.D., Ph.D., FACP, Co-Director, Virginia Cancer Specialists Research Institute. "This important dataset demonstrates positive clinical activity with adagrasib across molecular and clinical subgroups, including patients with treated and stable CNS metastases."

The Company also presented results from an exploratory, retrospective subgroup analysis from the Phase 2 NSCLC cohort of the KRYSTAL-1 study evaluating adagrasib in patients with KRASG12C-mutated NSCLC and stable, previously treated central nervous system (CNS) metastases (n=33). These results showed CNS-specific activity, including a 33% intracranial (IC) ORR by response assessment in neuro-oncology-brain metastases (modified RANO-BM). The IC DCR was 85% (95% CI: 68 – 95).

"The exploratory, retrospective subgroup analysis of adagrasib in patients with stable and previously treated CNS metastases showed intracranial tumor regression," added Dr. Spira. "These data are encouraging and contribute to the rapidly advancing science seeking to better understand how KRASG12C inhibitors like adagrasib can help improve patient outcomes."

Updated Findings from Pooled Analysis of KRYSTAL-1 NSCLC Cohorts
In addition to these results, the Company reported updated findings from a pooled analysis in a total of 132 patients from the KRYSTAL-1 study, including the registrational Phase 2 and Phase 1/1b NSCLC cohorts evaluating adagrasib at a dose of 600mg BID.

As of October 15, 2021, results from this pooled analysis showed an ORR of 44% and a disease control rate of 81% based on central independent review. The median DOR was 12.5 months and the median PFS was 6.9 months. With a January 15, 2022 data cutoff, (median duration of follow-up of 15.9 months) the median OS was 14.1 months. The safety and tolerability profile was consistent with the above reported findings for adagrasib in patients with advanced NSCLC. The Company plans to present full results from this pooled analysis at a future medical congress.

"The data from the registrational lung cancer cohort of KRYSTAL-1, including the clinical activity shown in patients with stable, previously treated CNS metastases, further support adagrasib’s unique profile," says Charles M. Baum, M.D., Ph.D., president, founder and head of research and development, Mirati Therapeutics, Inc. "Mirati is at the forefront of KRAS research, and we are pleased with the meaningfully positive clinical outcomes patients are experiencing with adagrasib, both in previously treated lung cancer and in other tumor settings."

On June 6, 2022, during an oral presentation at the 2022 ASCO (Free ASCO Whitepaper) Annual Meeting, the Company will present new, late-breaking results from the Phase 1b cohort of the KRYSTAL-1 study evaluating adagrasib in active, untreated CNS metastases (Abstract #LBA9009).

The adagrasib New Drug Application is currently being reviewed by the U.S. Food and Drug Administration (FDA) for Accelerated Approval (Subpart H) as a treatment for patients with NSCLC harboring the KRASG12C mutation who have received at least one prior systemic therapy. Adagrasib has also received Breakthrough Therapy Designation status from the FDA for the same indication. The Company has an ongoing confirmatory Phase 3 trial, KRYSTAL-12, evaluating adagrasib versus docetaxel who have been previously treated for metastatic NSCLC with a KRASG12C mutation.

Virtual Investor Event
Mirati Therapeutics will host an Investor Event on Monday, June 6, 2022, at 8:00 PM ET/7:00 PM CT.

Company executives will provide an overview of the adagrasib clinical data presented at the 2022 ASCO (Free ASCO Whitepaper) Annual Meeting and the Company’s broader lung cancer strategy, including in earlier lines of therapy.

Investors and the general public are invited to register and listen to a live webcast of the event through the "Investors and Media" section on Mirati.com. A replay of the event will be available shortly after the conclusion of the event.

Central Nervous System (CNS) Metastases in KRAS-Mutated Lung Cancer
The brain, along with the bone, adrenals, and liver are common sites of extra-thoracic metastases in NSCLC.[1]−3 CNS metastases occur in 27−42% of patients with KRASG12C-mutated NSCLC at diagnosis.1,4−6 Additionally, patients with CNS metastases and KRAS-mutated NSCLC may have poor outcomes, with median overall survival (OS) of approximately five months.7-9

About Adagrasib (MRTX849)
Adagrasib is an investigational, highly selective, and potent oral small-molecule inhibitor of KRASG12C that is optimized to sustain target inhibition, an attribute that could be important to treat KRASG12C-mutated cancers, as the KRASG12C protein regenerates every 24–48 hours. Adagrasib is being evaluated as monotherapy and in combination with other anti-cancer therapies in patients with advanced KRASG12C-mutated solid tumors, including NSCLC, colorectal cancer and pancreatic cancer. For more information visit Mirati.com/science.

Mirati has an Expanded Access Program (EAP) for investigational adagrasib for the treatment of eligible patients with KRASG12C-mutated cancers, regardless of tumor type, including patients with treated or untreated CNS metastases, in the U.S. Learn more about the EAP at Mirati.com/expanded-access-policy.

On May 26, 2022 Adicet Bio, Inc. (Nasdaq: ACET), a clinical stage biotechnology company discovering and developing first-in-class allogeneic gamma delta chimeric antigen receptor (CAR) T cell therapies for cancer, reported that an abstract detailing updated safety and efficacy data from the Company’s Phase 1 study of ADI-001 for the potential treatment of relapsed or refractory B-cell Non-Hodgkin’s Lymphoma (NHL) was made available as part of the 2022 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, to be held June 3-7, 2022 (Press release, Adicet Bio, MAY 26, 2022, View Source [SID1234615126]). The abstract provides a summary of clinical data as of a February 14, 2022, data-cut date.

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"We are very pleased to see the continued positive data resulting from our ongoing Phase 1 clinical trial evaluating ADI-001 in relapsed/refractory NHL. We believe that our allogeneic gamma delta CAR T cell therapy approach may improve complete response rate and durability by the complementary innate, adaptive and CAR-mediated anti-tumor response," said Chen Schor, President and Chief Executive Officer of Adicet. "We look forward to presenting updated data on safety, efficacy, pharmacokinetics and longer follow up, including available data from patients enrolled in dose level 3, at the upcoming 2022 ASCO (Free ASCO Whitepaper) Annual Meeting with a coinciding press release as well as a company webcast later that afternoon."

Data highlights as of the February 14, 2022 data-cut date included in the ASCO (Free ASCO Whitepaper) abstract were as follows:

Six evaluable patients were enrolled in dose level 1 (DL1; 30 million CAR+ cells) and dose level 2 (DL2; 100 million CAR+ cells), 33% (2/6) were female and the median age was 62 years (range 45-75). There were five patients with large B-cell lymphoma and one with mantle cell lymphoma. Indolent lymphomas, such as follicular lymphoma, are currently not enrolled in the study.
Overall, the patients were heavily pretreated with a median number of prior therapies of 3.5 (range 2-5) and had a poor prognostic outlook as indicated by the median International Prognostic Index (IPI) score of 3.5 (range 2-4). One patient previously progressed following two prior treatments with autologous anti-CD19 CAR T cell therapy (lisocabtagene maraleucel) prior to receiving ADI-001.
At Day 28, the overall response rate (ORR) and the complete response (CR) rate based upon independent central reading by PET/CT were 67% (4/6 patients).
As of the February 14, 2022 data-cut date, of the four patients who achieved CR after treatment with ADI-001:
Two patients remained in CR with ≥ three months post-treatment follow-up, including a triple-hit large B-cell lymphoma patient who had previously progressed following two administrations of autologous anti-CD19 CAR-T and a total of five lines of prior therapy.
As previously disclosed, one patient, a 66-year-old female who had responded to ADI-001, developed COVID-19 related pneumonia approximately two and a half months after ADI-001 administration and later died of complications from it, unrelated to ADI-001. This patient was previously reported as a partial response (PR) by local radiological assessment and has been assessed as a CR by independent central reading.
One patient with a CR had not reached the three-month assessment date as of the data-cut date for the ASCO (Free ASCO Whitepaper) abstract submission.
Safety data from the trial at the February 14, 2022 data-cut date were consistent with the previously reported well tolerated profile, with no occurrence of Grade ≥ 3 Cytokine Release Syndrome (CRS), Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) or Graft vs Host Disease. No dose-limiting toxicities were documented.
All response data have been determined per protocol by independent central reading of PET/CT per Lugano (2014) criteria.
The full abstract is available online on the ASCO (Free ASCO Whitepaper) website.

Updated data from a May 31, 2022 data-cut date will be presented during an oral presentation by Sattva Neelapu, M.D. Professor in the Department of Lymphoma/Myeloma at The University of Texas MD Anderson Cancer Center, at the ASCO (Free ASCO Whitepaper) Annual Meeting on June 6, 2022. Adicet will summarize the data from the May 31, 2022 data-cut date in a press release and provide additional information in a company webcast on June 6, 2022.

Details of the oral presentation are as follows:

Abstract Number: 7509
Abstract Title: A Phase 1 Study of ADI-001: Anti-CD20 CAR-engineered Allogeneic Gamma Delta (γδ) T cells in Adults with B-cell malignancies
Presenting Author: Sattva Neelapu, M.D., The University of Texas MD Anderson Cancer Center
Session Type/Title: Clinical Science Symposium/ Beating Bad Blood: The Power of Immunotherapy in Hematologic Malignancies
Date: Monday, June 6, 2022
Time: 8:00 AM-9:30 AM CDT

Adicet Investor Webcast/ Conference Call Information

The Company will host a conference call and webcast on June 6, 2022, at 4:30 p.m. ET to discuss the results. The live webcast of the presentation can be accessed under "Presentations & Events" in the investors section of the Company’s website at www.adicetbio.com or by dialing (877) 800-3802 (domestic) or +1 (615) 622-8057 (international) and reference the conference ID 5466375. The archived webcast will be available on the Company’s website beginning approximately two hours after the event.

About ADI-001

ADI-001 is an investigational allogeneic gamma delta CAR T cell therapy being developed as a potential treatment for relapsed or refractory B-cell NHL. ADI-001 targets malignant B-cells via an anti-CD20 CAR and via the gamma delta innate and T cell endogenous cytotoxicity receptors. Gamma delta T cells engineered with an anti-CD20 CAR have demonstrated potent antitumor activity in preclinical models, leading to long-term control of tumor growth. In April 2022, ADI-001 was granted Fast Track Designation by the U.S. Food and Drug Administration (FDA) for the potential treatment of relapsed or refractory B-cell NHL.

About the GLEAN Study

This Phase 1 study is an open-label, multi-center study of ADI-001 enrolling adults diagnosed with B-cell malignancies who have either relapsed, or are refractory to at least two prior regimens. The primary objectives of the study are to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of ADI-001, and to determine optimal dosing as a monotherapy. The study is expected to enroll approximately 75 patients. For more information about the clinical study design, please visit www.clinicaltrials.gov (NCT04735471).

On May 26, 2022 Caris Life Sciences(Caris), the leading molecular science and technology company actively developing and delivering innovative solutions to revolutionize healthcare reported that the company and partners within its Precision Oncology Alliance (POA) will collectively present 45 studies across more than 20 various solid tumor types at the 2022 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting from June 3-7, 2022 (Booth #22081) (Press release, Caris Life Sciences, MAY 26, 2022, View Source [SID1234615142]).

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"The breadth of research being presented at ASCO (Free ASCO Whitepaper) illustrates the power of comprehensive molecular profiling and large-scale collaboration between more than 60 sites to address some of the biggest challenges in cancer care and precision oncology today," said Chadi Nabhan, M.D., MBA, FACP, Chairman of the Caris Precision Oncology Alliance. "The findings of these studies could help improve outcomes for patients with difficult-to-treat cancers and pioneer new approaches to care across diverse tumor types and patient populations."

"At Caris, our goal is to enable clinicians to make the best treatment choices, researchers to discover new targets, and the biopharmaceutical industry to develop the next breakthrough medicines," said David Spetzler, M.S., Ph.D., MBA, President and Chief Scientific Officer of Caris. "These presentations show how our scientists and partners in the POA are using Caris’ unique AI-driven platform – which combines data from DNA (Whole Exome), RNA (Whole Transcriptome), and protein profiling with real-world clinical evidence from over 378,000 lifetime cases – to unravel the complexities of cancer. Ultimately, these discoveries could advance personalized cancer care and improve outcomes for many patients."

The Caris Precision Oncology Alliance includes 65 cancer centers and academic institutions in the United States and beyond. These institutions have early access to the extensive database and artificial intelligence platform within Caris to establish evidence-based standards for cancer profiling and molecular testing in oncology. By leveraging the comprehensive genomic, transcriptomic and proteomic data available through Caris molecular profiling, Caris seeks to provide this network with the ability to prioritize therapeutic options and determine which clinical trial opportunities may benefit their patients. POA members are also able to integrate with a growing portfolio of biomarker directed trials sponsored by biopharma. Additionally, as a member of the POA, institutions have access to Caris CODEai, the most comprehensive data solution in the industry with cancer treatment information and real-world clinical outcomes evidence for over 275,000 patients covering over 1 million data points per patient.

Three oral discussions focus on difficult to treat tumors and aggressive tumor types with low survival rates:

Comprehensive Genomic and Transcriptomic Characterization of Small Bowel Adenocarcinoma (Poster Number: 6)
June 4, 2022, 1:15-2:45 PM CDT

Biological and prognostic relevance of epigenetic regulatory genes in high-grade gliomas (HGGs) (Poster Number: 3570)
June 5, 2022, 11:30 AM-1:00 PM CDT

Surfaceome profiling revealed unique therapeutic vulnerabilities in transcriptional subtypes of small cell lung cancer (SCLC) (Poster Number: 142)
June 6, 2022, 11:30 AM-1:00 PM CDT
Other notable studies among the 45 accepted abstracts focus on key topics in oncology such as the tumor microenvironment, mechanisms of therapeutic resistance and rare biomarkers:

The tumor microenvironment and immune infiltration landscape of KRAS mutant pancreatic ductal adenocarcinomas (PDAC) compared to colorectal adenocarcinomas (CRC) (Poster Number: 127)
June 4, 2022, 8:00-11:00 AM CDT

Claudin 18 (CLDN18) gene expression and related molecular profile in gastric cancer (GC) (Poster Number: 36)
June 4, 2022, 8:00-11:00 AM CDT

The differential response to immune checkpoint inhibitors in colorectal and endometrial cancer patients according to different mismatch repair alterations (Poster Number: 418)
June 4, 2022, 8:00-11:00 AM CDT

Characterization of TIM3 and its ligands in colorectal cancer (Poster Number: 341)
June 4, 2022, 8:00-11:00 AM CDT

Exploring the nuances between BRCA1 and 2: a multiomic analysis (Poster Number: 456)
June 4, 2022, 1:15-4:15 PM CDT

S1314 Correlative analysis of ATM, RB1, ERCC2 and FANCC mutations and pathologic complete response (pT0) at cystectomy after neoadjuvant chemotherapy (NAC) in patients with muscle invasive bladder cancer (MIBC): implications for bladder preservation (Poster Number: 72)
June 4, 2022, 1:15-4:15 PM CDT

Reversion mutations in BRCA1 or BRCA2 genes: Resistant mechanism(s) in patients treated with platinum-based agents or poly (ADP-ribose) polymerase (PARP) inhibitors (Poster Number: 124)
June 5, 2022, 8:00-11:00 AM CDT

Characterization of MET exon 14 skipping alterations (METex14) in non–small cell lung cancer (NSCLC) using whole transcriptome sequencing (WTS) (Poster Number: 108)
June 6, 2022, 8:00-11:00 AM CDT
Poster and abstract summaries highlighting this research will be available onsite at Caris’ booth 22081. The full abstracts will be available through the official ASCO (Free ASCO Whitepaper) website on May 26.

On May 26, 2022 Adagene Inc. ("Adagene") (Nasdaq: ADAG), a company transforming the discovery and development of novel antibody-based therapies, reported the publication of data showing the potential best-in-class safety profile of its anti-CTLA-4 monoclonal antibody (mAb), ADG126. Interim results from the Phase 1 dose escalation portion of an ongoing Phase 1b/2 trial of ADG126 are published in an abstract on the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) meeting website in conjunction with the 2022 Annual Meeting taking place in Chicago from June 3-7, 2022 (Press release, Adagene, MAY 26, 2022, View Source [SID1234615159]).

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Key data in the abstract, titled "Phase 1 study of ADG126, a novel masked anti-CTLA-4 SAFEbody, that combines tumor-localized activation with strong Treg depletion and soft ligand blocking in patients with advanced solid tumors," include the following:

In this dose escalation of 16 patients with advanced metastatic solid tumors, approximately one third received three or more lines of prior therapies, and approximately one third had progressed from immuno-oncology (IO) therapy. ADG126 was administered to this heavily pretreated patient population intravenously as monotherapy once every three weeks at doses up to 10 mg/kg.
No dose-limiting toxicities or treatment-related SAEs were observed and only Grade 1 treatment related adverse events (TRAEs) were reported with repeat dosing across all dose levels; fatigue (19%) and pruritis (13%) were most common.
Plasma pharmacokinetics (PK) were approximately linear and the activated ADG126 accumulated steadily during repeat dosing across different dose levels. As the first clinical data validating the SAFEbody precision masking technology, the approximately 1.7-fold increase in half-life of total ADG126 is reflective of prolonged exposures of activated ADG126 in the tumor microenvironment (TME).
In an early indication of antitumor activity, two heavily pretreated patients with cold tumors (one ovarian and one uveal melanoma) showed durable reductions in target lesions (over 20%) and increased CD8+ T cells post-dosing. After the seventh cycle of ADG126 treatment at 1 mg/kg the ovarian cancer patient also showed a 77% reduction in CA-125 levels, an established biomarker of clinical benefit for ovarian patients. This activity is likely due to the accumulation of activated ADG126 in the TME upon repeat dosing at 1 mg/kg. The uveal melanoma patient was resistant/refractory to prior IO-IO combination therapy, having progressed on the combination of nivolumab and ipilimumab.
At the data cut-off of February 15, 2022, stable disease was seen in 5/16 patients, including the ovarian cancer and uveal melanoma patients. Dose escalation in this trial continues at 20 mg/kg and dose expansion has started at 10 mg/kg.
Commenting on the findings, Dr. Gary Richardson, OAM, MBBS, FRACP, Group Director at Cabrini Health Research, Neil Beauglehall Endowed Chair, Medical Oncology Research, and Professor of Medicine at Monash University, Australia, said, "With the emerging clinical data evaluating this novel immunotherapy candidate ADG126, a masked anti-CTLA-4 SAFEbody, we have the opportunity to detangle safety from efficacy, and deeply understand the benefits of Treg depletion while we optimize anti-CTLA-4 therapy as a cornerstone of future therapy. Another exciting and surprising aspect of these interim findings is that we see early signals of efficacy in certain ‘cold’ tumors with SAFEbody ADG126, which further builds on prior clinical evidence with its parental antibody ADG116, targeting a unique epitope of CTLA-4 to enable not only a safer but potentially better therapy than the options we have available today."

ADG126 SAFEbody applies precision-masking technology to the parental anti-CTLA-4 antibody, ADG116, for conditional activation in the TME to expand the therapeutic index and further address safety concerns with existing CTLA-4 therapies. Binding to the same unique epitope as ADG116, the masked ADG126 is designed to provide enhanced safety and efficacy profiles due to the combination of the potent Treg depletion in the TME and soft ligand blocking.

"Following these monotherapy dose escalation results, we look forward to releasing further data in coming months to confirm if the strong safety profile of ADG126 is preserved in combination with anti-PD-1 therapy, consistent with our preclinical observations," said Peter Luo, Ph.D., Co-founder, Chief Executive Officer and Chairman of Adagene.