On May 26, 2022 Oncternal Therapeutics, Inc. (Nasdaq: ONCT), a clinical-stage biopharmaceutical company focused on the development of novel oncology therapies, reported updated interim clinical data from the ongoing Phase 1/2 CIRLL (Cirmtuzumab and Ibrutinib targeting ROR1 for Leukemia and Lymphoma) clinical trial, that will be presented in a poster presentation at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2022 Annual Meeting (Press release, Oncternal Therapeutics, MAY 26, 2022, View Source [SID1234615160]). In the CIRLL study, zilovertamab, an investigational anti-ROR1 monoclonal antibody, is being evaluated in combination with ibrutinib in patients with mantle cell lymphoma (MCL) and chronic lymphocytic leukemia (CLL). The clinical trial is being conducted in collaboration with the University of California San Diego (UC San Diego) and has been partially funded by the California Institute for Regenerative Medicine (CIRM).

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The updated interim data will be presented as a poster discussion session at the Hematologic Malignancies—Lymphoma and Chronic Lymphocytic Leukemia session on Saturday, June 4, 2022 as part of the ASCO (Free ASCO Whitepaper) 2022 Annual Meeting:

Poster Title: Phase 1/2 study of zilovertamab and ibrutinib in mantle cell lymphoma (MCL) or chronic lymphocytic leukemia (CLL)
Abstract Number: 7520
Session Name: Hematologic Malignancies—Lymphoma and Chronic Lymphocytic Leukemia
Session Date and Time: June 4, 2022 from 8:00-11:30 am (Central Time)
"The interim data update presented today further strengthens our confidence in the significant clinical value the combination of zilovertamab and ibrutinib can deliver to MCL and CLL patients. Solid objective response rate (ORR) of 85% and median progression-free survival (PFS) of 36 months in heavily pre-treated MCL patients in our CIRLL study support our Phase 3 registrational study ZILO-301, which we plan to initiate in the third quarter," said James Breitmeyer, M.D., Ph.D., Oncternal’s President and CEO. "We continue to be especially intrigued by the encouraging and robust response rate across multiple populations of high-risk MCL and CLL patients, most notably the prolonged PFS seen for those that express the p53 mutation, a particularly challenging population for BTK inhibitors. This is further proof that the combination is very active, and we believe it may address important unmet medical needs in difficult-to-treat patients with aggressive forms of hematological malignancies."

The results that will be presented in poster form and reviewed in a poster discussion at the ASCO (Free ASCO Whitepaper) 2022 Annual Meeting include 33 patients with relapsed/refractory MCL enrolled in the dose-finding and dose-expansion cohorts of the CIRLL clinical trial (Part 1 + Part 2), of whom 27 were evaluable for efficacy as of the April 8, 2022 data cut-off date.

Patients had high-risk factors and were heavily pre-treated at study entry, with 52% having a high Ki-67 proliferative index (≥30%), and 46% having an intermediate or high sMIPI prognostic score.
The ORR of 85% (23 of 27 evaluable patients) includes recently enrolled patients with relatively short follow-up time.
The complete response (CR) rate was 41% (11 of 27 evaluable patients). CRs have remained durable for up to 35 months.
The partial response (PR) rate was 44% (12 of 27 evaluable patients), and the stable disease (SD) rate was 7% (2 of 27 evaluable patients), for a total clinical benefit rate (CR, PR and SD) of 93%.
The ORR and median duration of response (DOR) were also favorable in patients with other high-risk features associated with disease difficult-to-treat with BTK inhibitors:
P53 mutation: ORR of 83%; median DOR of 13.8 months (95% CI: 11.9, NE), median PFS of 17.3 months (95% CI: 2.9, NE) and a landmark PFS over 80% at 15 months
Ki-67 ≥30%: ORR of 86%; median DOR not reached (95% CI: 13.7, NE)
>1 prior systemic therapy: ORR of 83%; median DOR not reached for patients receiving two prior lines of systemic therapy and 34 months (95% CI: 13.8, 34.1) for patients with ≥ 3 prior lines of systemic therapy
Prior treatment with ibrutinib: ORR of 80% (4/5), with two CRs, two PRs and one SD
Median PFS was 35.9 months for all patients with MCL after a median follow-up of 14.4 months (95% CI: 11.4, 19.3), regardless of number of prior systemic therapies. Further, median PFS had not been reached for patients achieving a CR.
Historical data published for single agent ibrutinib for 370 patients with relapsed/refractory MCL from three clinical trials showed an ORR of 66%, CR rate of 20% and median PFS of 12.8 months (Rule et al. 2017, British Journal of Haematology). Historical data in 20 patients with p53 mutation showed an ORR of 55% and median PFS of 4.0 months (Rule, 2019).
Thirty-four patients with CLL enrolled in the dose-finding and dose-confirming cohorts of this clinical trial (Part 1 & Part 2) as of the April 8, 2022 data cut-off date, were all evaluable for efficacy. Patients had high-risk factors, and most were heavily pre-treated at study entry, with 71% having RAI staging ≥2 and a median of two systemic prior therapies (range 1-9).

The ORR was 91% (31 of 34 evaluable patients).
The CR rate was 9% (3 of 34 evaluable patients).
The clinical benefit rate was 100%, with 28 of 34 (82%) evaluable patients achieving a PR, and three patients (9%) had SD.
The median PFS had not been reached for all patients with CLL, whether treatment-naïve or those with relapsed refractory disease.
Landmark PFS was 100% at 36 months for CLL patients with 1 or 2 prior lines of therapy, which compares favorably to historical ibrutinib monotherapy of ~ 73% (Byrd. 2019).
For patients with CLL who had received > 2 prior lines of therapy, the landmark PFS was over 85% at 24 months and 70% at 36 months, which compares favorably to the historical ibrutinib monotherapy landmark PFS at 24 and 36 months of ~ 65% and ~ 50%, respectively (Byrd. 2019).
Thirty-one patients with CLL have also been enrolled in the randomized efficacy cohort of this clinical trial (Part 3), of which 23 were evaluable for efficacy. Data on this cohort are maturing. The median PFS had not been reached for either group as of the April 8, 2022 cut-off date after 24 months of follow up.

The combination of zilovertamab plus ibrutinib has been well tolerated, with treatment emergent adverse events consistent with those reported for ibrutinib alone. There have been no dose-limiting toxicities and no serious adverse events attributed to zilovertamab alone. In patients with MCL, Grade 3-4 neutrophil decrease was documented in 9.1% of patients with zilovertamab plus ibrutinib, compared to 29% for ibrutinib alone from its registration study.

About the CIRLL Clinical Trial
The CIRLL clinical trial (CIRM-0001) is a Phase 1/2 trial evaluating zilovertamab in combination with ibrutinib in separate groups of patients with CLL or MCL. Enrollment of the dose-finding cohorts in CLL and MCL, dose-expansion cohort in CLL and MCL and randomized Phase 2 cohort in CLL has been completed. An additional dose-expansion cohort of up to 10 patients with marginal zone lymphoma (MZL) has recently been added. Enrollment is expected to begin in Q2 2022. Additional information about the CIRM-0001 clinical trial and other clinical trials of zilovertamab may be accessed at ClinicalTrials.gov.

About Zilovertamab
Zilovertamab (formerly designated cirmtuzumab) is an investigational, humanized, potentially first-in-class monoclonal antibody targeting Receptor tyrosine kinase-like Orphan Receptor 1 (ROR1). Zilovertamab is currently being evaluated in a Phase 1/2 clinical trial in combination with ibrutinib for the treatment of patients with MCL, chronic lymphocytic leukemia (CLL) or MZL, in a collaboration with the University of California San Diego (UC San Diego) School of Medicine and the California Institute for Regenerative Medicine (CIRM). In addition, Oncternal is supporting two investigator-sponsored studies being conducted at the UC San Diego School of Medicine, a Phase 1b clinical trial for patients with metastatic castration-resistant prostate cancer (mCRPC), and a Phase 2 clinical trial of zilovertamab in combination with venetoclax, a Bcl-2 inhibitor, for patients with relapsed/refractory CLL. Both are open for enrollment.

ROR1 is a potentially attractive target for cancer therapy because it is an onco-embryonic antigen, not usually expressed on adult cells, but its expression confers a survival and fitness advantage when reactivated and expressed by tumor cells. Researchers at the UC San Diego School of Medicine discovered that targeting a critical epitope on ROR1 was key to specifically inhibiting ROR1-expressing tumors. This led to the development of zilovertamab which binds this critical epitope of ROR1, highly expressed on many different cancers but not on normal tissues. Preclinical data showed that when zilovertamab bound to ROR1, it blocked Wnt5a signaling, inhibited tumor cell proliferation, migration and survival, and induced differentiation of the tumor cells. The FDA has granted Orphan Drug Designations to zilovertamab for the treatment of patients with MCL and CLL/small lymphocytic lymphoma. Zilovertamab is in clinical development and has not been approved by the FDA for any indication.

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.

On May 26, 2022 Invitae (NYSE: NVTA), a leading medical genetics company, reported eight studies to be presented at the 2022 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting held in Chicago from June 3-7, 2022 (Press release, Invitae, MAY 26, 2022, View Source [SID1234615158]). While the research covers a variety of cancer types, stages and patient demographics, all of the data underscore the importance of universal genetic testing to improve health outcomes for all cancer patients.

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Invitae’s (NVTA) mission is to bring comprehensive genetic information into mainstream medical practice to improve the quality of healthcare for billions of people. www.invitae.com (PRNewsFoto/Invitae Corporation)

Inherited genes impact risk for developing melanoma

Melanoma—the most frequent cause of skin cancer-related deaths—is often perceived as a cancer caused by environmental factors. While sun exposure plays a role in most melanoma tumors, a new, first-of-its-kind study by Cleveland Clinic and Invitae found that genetics also play a critical role in the likelihood of developing melanoma. In fact, the study found that 15% of individuals with melanoma have inherited variants in a variety of genes associated with cancer predisposition syndromes, demonstrating multiple potential etiologies. What’s more, genes previously associated with inherited melanoma comprised less than half of pathogenic variants (48%); and the majority of germline variants were in cancer predisposition genes that are not traditionally associated with melanoma. This study shows that all patients with melanoma should undergo genetic testing, whether or not they have a family history of cancer, or a personal history of sun exposure.

"Previously, it was thought that few melanoma patients would demonstrate a pathogenic germline variant in cancer susceptibility genes indicating an inherited component to their melanoma risk," said Joshua Arbesman, M.D., dermatologist at Cleveland Clinic and senior author of the study. "Our results, however, suggest that about 1 in 6 melanoma patients would have an inherited variant in cancer genes. This means that these particular patients would benefit from cancer specific screening (separate from skin screening) that could catch other cancers earlier. We found similar results using multiple datasets with variable inclusion criteria, suggesting this may be potentially applicable to many melanoma patients."

Research shows prostate cancer testing guidelines out of date

A separate study of prostate cancer patients confirmed similar findings that limiting genetic testing to those patients who meet NCCN guidelines deprives individuals and clinicians of actionable information. In data from the ongoing PROCLAIM study, conducted primarily in community urology clinics, 50% of pathogenic variants in patients with prostate cancer would be missed if genetic testing were done based on NCCN guidelines. The study also showed current guidelines are poorly suited to detect pathogenic variants in traditionally underrepresented populations, suggesting a transition to universal testing may be the most expeditious strategy to mitigate this potential healthcare disparity. Appropriately, patients with cancer-linked pathogenic variants in the study were more likely to have recommendations made by their clinicians regarding changes to treatment, follow up and cascade testing than those with negative or uncertain results. Clinicians made genetics-based recommendations across the spectrum of patients tested, including those not meeting NCCN criteria, and those with low-grade and non-metastatic disease.

"Guidelines from national and international oncologic societies are regularly updated but not always as quickly as our understanding of gene-disease relationships in the rapidly evolving field of genomic sequencing, and thus there are real world implications affecting patient-physician decision making as well as patient access to affordable and geographically accessible genetic testing," said Dr. Neal Shore, lead author of the study. "This study shows that germline genetic testing has a significant impact on prostate cancer patient care, and that urologists, oncologists, their patients and patients’ family members would benefit from making germline genetic testing a routine practice for all prostate cancer patients."

Genetic changes impact colorectal cancer care

In a third study of more than 34,000 colorectal cancer patients—the largest study of its kind to date—researchers found that 13% of patients had inherited pathogenic variants that could potentially impact patient eligibility for precision therapy, access to clinical trials and/or inform screening for future cancers. This study, in collaboration with investigators at the University of Pennsylvania Perelman School of Medicine, showed rates > 7.8% of clinically actionable pathogenic gene variants independent of age group, racial/ethnic group and panel size. The study saw a lower rate of pathogenic variants in known cancer genes in Hispanic patients and a higher rate of variants of uncertain significance (VUS) in Black, Asian and Hispanic patients. This underscores the historical underrepresentation of these patients in genetics studies, and the ongoing need to mitigate the associated healthcare disparities.

"In the United States, colorectal cancer is the third leading cause of cancer-related deaths in men and in women, and the second most common cause of cancer deaths when men and women are combined," said Ed Esplin, M.D., Ph.D., FACMG, FACP, clinical geneticist at Invitae. "The genetic variants we inherit play a crucial role in providing patients access to approved precision therapies and clinical trials for colorectal cancer treatment, and to quantify and mitigate the risk of colorectal cancer in their at-risk family members. This study shows the importance of broadening genetic testing criteria to include all patients with colorectal cancer, regardless of age, race/ethnicity or family history."

Additional clinical research from Invitae at ASCO (Free ASCO Whitepaper)

Invitae is presenting additional research at ASCO (Free ASCO Whitepaper) in collaboration with academic institutions and research partners that showcase the importance of genetic testing to guide cancer diagnosis and precision medicine treatment. This effort is consistent with the primary objectives of the Cancer Moonshot to reduce the death rate from cancer by 50 percent and improve the experience of people and their families living with cancer. All of the presentations highlight Invitae’s commitment to improving the adoption of germline genetic testing among physicians and people living with cancer, highlighting the impact of cancer genetics on cancer patients from underserved populations, and effectively illustrating its clinical utility in improving patient care.

2022 ASCO (Free ASCO Whitepaper) presentations:

Poster 60/Abstract 4569: Titled: Germline variants across self-reported racial populations with urothelial carcinoma (UC). Presenter: Amin Nassar, M.D. — Saturday, June 4, 2022 at 1:15 p.m. CDT.
Abstract 10500: Titled: Democratizing germline genetic testing and its impact on prostate cancer clinical decision-making. Presenter: Neal D. Shore, M.D. — Monday, June 6, 2022 at 8:00 a.m. CDT.
Abstract 10504: Titled: Clinical implications of germline genetic testing stratified by ethnicity in a large colorectal cancer cohort. Presenter: Sarah Coughlin, M.D. — Monday, June 6, 2022 at 8:00 a.m. CDT.
Poster 464/Abstract 10589: Titled: Integrated germline and somatic cancer testing provides opportunity to identify cancer risk and resolve variant origins. Presenter: King Das, M.D. — Monday, June 6, 2022 at 1:15 p.m. CDT.
Poster 455/Abstract 10580: Titled: Implementation of universal, pan-cancer germline genetic testing in cancer patients in Jordan. Presenter: Hikmat Abdel-Razeq, M.D. — Monday, June 6, 2022 at 1:15 p.m. CDT.
Poster 463/Abstract 10588: Titled: Universal genetic testing versus guideline-directed testing for hereditary cancer syndromes among traditionally underrepresented patients in a community oncology program. Presenter: Jeremy Clifton Jones, M.D. — Monday, June 6, 2022 at 1:15 p.m. CDT.
Poster 401/Abstract 10523: Titled: Germline predisposition in oncologic and dermatologic melanoma cohorts. Presenter: Pauline Funchain, M.D. — Monday, June 6, 2022 at 4:30 p.m. CDT.
Online Publication: Titled: Patterns and prevalence of pathogenic germline mutations using multi-gene panel testing in patients with ovarian cancer. The Jordanian Exploratory Cancer Genetics (Jo-ECAG) ovarian study. Lead Author Hikmat Abdel-Razeq, M.D.

On May 26, 2022 Surface Oncology (Nasdaq: SURF), a clinical-stage immuno-oncology company developing next-generation immunotherapies that target the tumor microenvironment, reported the presentation of new clinical data on SRF388, a potential first-in-class IL-27 antibody (Press release, Surface Oncology, MAY 26, 2022, View Source [SID1234615157]). Data from the Phase 1/1b clinical trial of SRF388 as a monotherapy and in combination with pembrolizumab, Merck’s anti-PD-1 therapy, will be presented in an oral abstract session at the 2022 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting.

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"In the ongoing SRF388 Phase 1 trial, we observed three confirmed partial responses across three different indications with multiple other patients experiencing durable clinical benefit in the form of disease stabilization," said Alison O’Neill, M.D., chief medical officer at Surface Oncology. "While still early, these findings are compelling and support our view that SRF388 holds exciting potential in the treatment of a variety of tumor types, particularly in combination with other immuno-oncology therapies."

"SRF388 is a potential first-in-class cytokine antagonist with a unique mechanism of anti-tumor activity that is showing encouraging early efficacy with a favorable safety and tolerability profile even in heavily pre-treated patients," added Aung Naing, M.D., professor of Investigational Cancer Therapeutics at The University of Texas MD Anderson Cancer Center. "The biology of the pathway, strong preclinical data, and tolerability of SRF388 support the potential for IL-27 blockade to complement PD-1 inhibition and other standard-of-care therapies across a range of cancers."

SRF388 Data Highlights:

Confirmed partial responses (PR) were observed in two patients who received SRF388 monotherapy treatment: one in non-small-cell lung cancer (NSCLC) (previously reported) and one in clear cell renal cell carcinoma (RCC). In addition, a PR was observed in a patient who was treated with SRF388 in combination with pembrolizumab for hepatocellular carcinoma (HCC). The patient with HCC was refractory to two prior VEGFR TKIs, while the patients with NSCLC and RCC had both progressed on prior anti-PD-(L)1 therapy.
SRF388 was well tolerated at all doses investigated (up to 20 mg/kg), with no dose-limiting toxicity or high-grade safety signals observed.
Encouraging pharmacodynamic data demonstrated that, after SRF388 administration, circulating IFNg increased —an on-target mechanism of action indicating increased immune activation.
Based on these efficacy data, the criteria for opening Stage 2 of the RCC monotherapy cohort was met. SRF388 is also being evaluated in NSCLC as a monotherapy and in combination with pembrolizumab, as well as in triplet therapy with atezolizumab and bevacizumab in first-line HCC.
SRF388 Clinical Program Updates:

Surface will initiate a new Simon two-stage expansion study of SRF388 in combination with pembrolizumab in up to 40 patients with relapsed/refractory NSCLC.
Data from multiple SRF388 cohorts, including in NSCLC and first-line HCC, are anticipated in the first half of 2023.
ASCO Presentation Details:

Title: First-in-human study of SRF388, a first-in-class IL-27 targeting antibody, as monotherapy and in combination with pembrolizumab in patients with advanced solid tumors
Abstract: 2501
Session Type/Title: Oral abstract session / Developmental Therapeutics – Immunotherapy
Session Date and Time: Saturday, June 4, 2022, 1:15 p.m. – 4:15 p.m. CDT
Slides from the ASCO (Free ASCO Whitepaper) presentation will be posted on the Surface Oncology website following the conclusion of the session.

About SRF388
SRF388 is a fully human anti-IL-27 antibody designed to inhibit the activity of this immunosuppressive cytokine. Surface Oncology has identified particular tumor types, including liver, kidney and lung cancer, where IL-27 appears to play an important role in the immunosuppressive tumor microenvironment and may contribute to resistance to treatment with checkpoint inhibitors. SRF388 targets the rate-limiting p28 subunit of IL-27, and preclinical studies have shown that treatment with SRF388 blocks the immunosuppressive biologic effects of IL-27, resulting in immune cell activation in combination with other cancer therapies including anti-PD-1 therapy, as well as potent anti-tumor effects as a monotherapy. Furthermore, Surface Oncology has identified a potential biomarker associated with IL-27 that may be useful in helping to identify patients most likely to respond to SRF388. In November 2020, Surface announced that SRF388 was granted Orphan Drug designation and Fast Track designation for the treatment of refractory hepatocellular carcinoma from the FDA.

On May 26, 2022 Advaxis, Inc. (OTCQX: ADXS), a clinical-stage biotechnology company focused on the development and commercialization of immunotherapy products, reported the publication of updated results from the clinical trial of the lead asset from its ADXS-HOT off-the-shelf, cancer-type specific, immunotherapy program (Press release, Advaxis, MAY 26, 2022, View Source [SID1234615156]).

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These results from the clinical study ADXS-503-101 evaluating the ADXS-503 construct, which is designed to target certain cancers’ commonly occurring hotspot mutations and other tumor-associated antigens, will be presented at the ASCO (Free ASCO Whitepaper) Annual Meeting to be held on June 4-7, 2022, along with the trial design of the study of the second construct from the ADXS-HOT program, ADXS-504.

The goals of this Phase 1/2 open-label trial are to evaluate safety, tolerability, antitumor activity and immune-correlative data of ADXS-503 administered in combination with KEYTRUDA in patients with metastatic NSCLC. In Part B of this study, ADXS-503 is added-on to KEYTRUDA within 12 weeks of the first scan showing disease progression following treatment with KEYTRUDA. In Part C, both drugs are administered to previously untreated patients. The study design of the Phase 1 investigator-sponsor study of ADXS-504 for patients with biochemically recurrent prostate cancer at Columbia University, Herbert Irving Comprehensive Cancer Center NYC, will also be presented.

Key presentation highlights:

Poster Title: "A phase 2 study of an off-the-shelf, multi-neoantigen vector (ADXS-503) in patients with metastatic non-small-cell lung cancer either progressing on prior pembrolizumab or in the first-line setting"
Presenter: Gregory J. Gerstner, M.D., Illinois Cancer Care
Session Type: Poster Session – Hall A
Session Title: "Lung Cancer—Non-Small Cell Metastatic"
Date and Time: June 6, 2022, 8-11 AM (CDT)

Key study characteristics and takeaways:

Part B: 14 patients failing pembrolizumab as last therapy have been treated with ADXS-503 + pembrolizumab (Dose Level 1) with all patients evaluable for safety and efficacy
Overall response rate (ORR) was 14% (2/14) and Disease Control Rate (DCR) was 36% (5/14)
Two durable partial responses (PR) sustained for over 9 months and 21 months, respectively
Three durable cases of stable disease (SD) lasting for over 3, 5 and 14 months, respectively
Patients who seem to achieve clinical benefit in Part B of the study include those with PD-L1 expression ≥ 50% and those with prior pembrolizumab monotherapy exposure ≥ 12 months and/or with DCR > 6 months
Part C: 3 patients have received ADXS-503 + pembrolizumab in the 1st-line metastatic setting with all patients evaluable for safety and efficacy
Data continue to show a DCR of 67% (2/3) in the first three evaluable patients in Part C
Poster Title: "Immunogenicity and disease control induced by a multi-neoantigen vaccine (ADXS-503) in patients with metastatic non-small-cell lung cancer who have progressed on pembrolizumab"

Presenter: Dr. Aaron E. Lisberg, M.D., UCLA
Session Type: Poster Session – Hall A
Session Title: "Lung Cancer—Non-Small Cell Metastatic"
Date and Time: June 6, 2022, 8-11 AM (CDT)

Key takeaways: Long-term follow up of immune correlative markers suggest that ADXS-503 leads to durable clinical benefit in select patients through:

the production of cytokines with periodic pro-inflammatory and anti-tumoral effects supporting innate and adaptive immunity
the activation of Natural Killer (NK) cells in tumor control
the induction of proliferation and activation of previously exhausted CD8+ T-cells facilitating reaction to hotspot mutation antigens, tumor associated antigens (TAAs), and antigen spreading.
The activation of various subsets of memory CD8+ T cells
Poster Title: "A phase I study of ADXS-504, a cancer type specific immunotherapy, for patients with biochemically recurrent prostate cancer"

Presenter: Karie Runcie, M.D., Columbia University
Session Type: Poster Session – Hall A
Session Title: "Trials in Progress"
Abstract Number: TPS5115
Date and Time: June 6, 2022, 1:15-4:15 CDT (CDT)

"The correlation of durable clinical benefit with long-term immunological surveillance data from Part B of the ADXS-503 study is extremely encouraging," said Ken Berlin, President and CEO of Advaxis. "We not only observe a competitive ORR by adding-on ADXS-503 in patients failing pembrolizumab, but we also now better understand how ADXS-503 may reverse the exhaustion or enhance the activity of pembrolizumab in these cases," he concluded. "The immunogenicity studies tend to demonstrate that ADXS-503 does more than just activate antigen-specific T cells as part of the adaptive response in Part B patients. The clinical benefit may also be derived from the serial elevation of certain serum cytokines throughout the course of therapy as well as from the activation of NK and induction of memory T cells. These pleotropic effects of Lm vectors, which had been documented in preclinical models and now shown in the ADXS-503 trial, help to differentiate ADXS-503 from other vaccine platforms," added Andres Gutierrez, EVP and Chief Medical Officer of Advaxis. "Importantly, those effects are induced safely and without the use of adjuvant agents," he concluded.

Enrollment in Part B will continue up to a total of 18 patients to further evaluate if ADXS-503 is able to achieve ORR of ≥20% in patients progressing on pembrolizumab therapy, while Part C may enroll up to 25 patients.