On June 4, 2021 Notable Labs Inc., a leader in technology-powered life science with a proprietary platform for predicting patient outcomes and accelerating precision drug development, reported top-line results from its clinical response prediction technology platform in a pediatric acute myeloid leukemia (AML) study to be presented at the 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting to be held June 4th-8th (Press release, Notable Labs, JUN 4, 2021, View Source [SID1234583542]). The data will be presented by Dr. Alexandra Stevens at Texas Children’s Cancer Center and highlights the correlation of functional drug sensitivity screening using Notable’s predictive technology platform with clinical outcomes of pediatric patients.

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In the exploratory study, blood or bone marrow samples from 22 de novo pediatric AML patients prior to receiving pre-induction chemotherapy were processed using Notable’s predictive technology platform. Chemosensitivity profiles across a broad spectrum of ex vivo conditions were analyzed and integrated into a predictive measure for individual patients. This measure of ex vivo drug sensitivity correlated with the patients’ clinical results of minimal residual disease and one year relapse-free survival.

"Our collaboration with one of the leading pediatric medical centers further demonstrates the potential of Notable’s prediction technology in identifying and fast-tracking combination therapies in a real-world situation." said Dr. Thomas Bock, CEO of Notable. Dr. Stevens added, "These results are a critical step forward towards our vision of precision medicine where treatments are focused on those patients who will clinically respond, especially for hard-to-treat patient populations."

Details of the presentation are as follows:

Poster Presentation

Title: Ex Vivo Drug Sensitivity Assay Correlates with Clinical Response in Pediatric AML
Session Name: Poster Session: Pediatric Oncology
Abstract Number: 10032
Presentation Time: Available beginning June 4th, 2021

On June 4, 2021 Surface Oncology (Nasdaq: SURF), a clinical-stage immuno-oncology company developing next-generation immunotherapies that target the tumor microenvironment, reported a clinical trial collaboration with Roche to evaluate SRF388, Surface’s investigational anti-IL-27 antibody, in combination with Roche’s atezolizumab and bevacizumab in patients with treatment-naïve hepatocellular carcinoma (HCC) (Press release, Surface Oncology, JUN 4, 2021, View Source [SID1234583559]).

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Atezolizumab plus bevacizumab has been shown to significantly improve overall survival and, as reflected in many global clinical practice guidelines, is the new standard of care for unresectable or metastatic HCC. Evolving preclinical and epidemiologic data suggest a significant role for the immunosuppressive cytokine IL-27 in HCC and in resistance to PD-1 pathway blockade. Therefore, the addition of SRF388 to the proven efficacy of the atezolizumab/bevacizumab regimen has the potential to further improve outcomes in this challenging disease.

"At Surface, we are committed to identifying and accelerating the delivery to patients of life-changing treatments, whether as a single agent or in scientifically and clinically appropriate combinations," said Alison O’Neill, M.D., chief medical officer at Surface Oncology. "This collaboration leverages Roche’s deep experience in hepatocellular carcinoma and Surface’s commitment to rationally and rapidly develop SRF388, a first-in-class antibody against IL-27, to provide meaningful benefit to patients with liver cancer."

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 and kidney 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 hepatocellular carcinoma from the FDA.

On June 4, 2021 Provectus (OTCQB: PVCT) reported that preliminary full study data from the Company’s Phase 1 clinical trial of investigational cancer immunotherapy PV-10 (rose bengal disodium) for the treatment of neuroendocrine tumors (NET) metastatic to the liver (mNET) refractory to somatostatin analogs (SSAs) and peptide receptor radionuclide therapy (PRRT) (NCT02693067) is be presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2021 Annual Meeting, held June 4-8 online (Press release, Provectus Biopharmaceuticals, JUN 4, 2021, View Source [SID1234583575]).

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Highlights from the mNET Presentation at ASCO (Free ASCO Whitepaper) 2021:

Baseline and disease characteristics
12 patients; 50% male; median age of 66 years (range 47-79)
Primary tumor sites: 7 small bowel (58%), 2 pancreas (17%), 1 caecal (8%), and 2 unknown (17%)
NET grades: 5 Grade 1 (42%) and 7 Grade 2 (58%)
Refractory to SSA and PRRT; symptomatic progressive disease
PV-10 treatment summary
Median of 1 hepatic NET lesion injected (range 1-4); median of 1 injection cycle (range 1-4); 8 patients (75%) received 1 PV-10 treatment
Safety
Mild-to-moderate post-procedure pain reported by most patients
Grade 3 photosensitivity reaction in 1 patient, Grade 3 elevation of hepatic enzymes in 1 patient, and carcinoid flare in 2 patients
Injected lesion efficacy (RECIST 1.1)
42% partial response (PR) and 42% objective response rate (ORR)
Patient-level efficacy (RECIST 1.1)
83%a disease control rate (DCR)
Progression-free survival (PFS): median 9.2 months (range 1.0-41.8)
Overall survival (OS): median 22.5 months (range 5.5-41.8); 6 patients (50%) undergoing response follow-up at the data cut-off of April 30, 2021
Immune response
Upregulation of NK cells and activated CD4+ T cells was observed in peripheral blood collected 7 and 28 days post-PV-10 injection
Biomarkers and quality of life (QOL)
Chromogranin A levels remained stable in 10 patients (83%)
QOL assessments showed stable or improved carcinoid symptoms and global health status in most patients
a Typographical error on the poster

A copy of the poster is available on Provectus’ website at View Source

This clinical trial, a single-center study at The Queen Elizabeth Hospital (TQEH) in Adelaide, Australia that completed enrollment in 2020, is led by Tim Price, MBBS, DHlthSc (Medicine), FRACP, Head of Clinical Oncology Research and Chair of the combined Hematology and Medical Oncology Unit at TQEH and Clinical Professor in the Faculty of Medicine at the University of Adelaide. The primary endpoint of the trial is safety. Secondary endpoints include ORR of injected target and measurable bystander lesions, target lesion somatostatin receptor expression, and biochemical response. Disease response assessments are conducted by independent review using Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Six patients in the first cohort each received one percutaneously-administered injection of PV-10 to one target lesion per treatment cycle. Patients in the six-person second cohort can receive PV-10 injections of multiple lesions per cycle.

Dominic Rodrigues, Vice Chair of the Company’s Board of Directors, said, "The vast majority of patients with neuroendocrine cancer present with liver metastases, and their prognosis is poor. PV-10 treatment of these hepatic tumors in heavily pre-treated patients resulted in durable systemic clinical benefit and evidence of immunotherapeutic activity in an otherwise immunologically cold tumor type."

Mr. Rodrigues added, "Provectus’ PV-10 development program for visceral hepatic tumors, led by more recent clinical study of neuroendocrine cancer and uveal melanoma, has not elicited any safety concerns and provided encouraging evidence of local and systemic response and disease control in refractory patient populations. Numerous liver metastases of defined tumor types have been treated in this program, including hepatoma, colorectal, lung, pancreatic, ovarian, cutaneous melanoma, breast, neuroendocrine, and uveal melanoma."

About PV-10

Intralesional (IL) administration of PV-10 for the treatment of solid tumor cancers can yield immunogenic cell death within hours of tumor injection, and induce tumor-specific reactivity in circulating T cells within days.1,2,3 This IL PV-10-induced functional T cell response may be enhanced and boosted in combination with immune checkpoint blockade (CB).4 In CB-refractory advanced cutaneous melanoma, IL PV-10 may restore disease-specific T cell function, which may also be prognostic of clinical response. IL PV-10 has been administered to over 450 patients with cancers of the skin and of the liver. It is administered under visual, tactile or ultrasound guidance to superficial malignancies, and under CT or ultrasound guidance to tumors of the liver. Systemic administration of PV-10 is also undergoing preclinical study as prophylactic and therapeutic treatments for refractory and high-risk adult solid tumor cancers, and as a treatment for relapsed and refractory blood cancers.

About Rose Bengal Disodium

RBD is 4,5,6,7-tetrachloro-2′,4′,5′,7′-tetraiodofluorescein disodium, a halogenated xanthene and Provectus’ proprietary lead molecule. Provectus’ current Good Manufacturing Practices (cGMP) RBD is a proprietary pharmaceutical-grade drug substance produced by the Company’s quality-by-design (QbD) manufacturing process to exacting regulatory standards that avoids the formation of uncontrolled impurities currently present in commercial-grade rose bengal. Provectus’ RBD and cGMP RBD manufacturing process are protected by composition of matter and manufacturing patents as well as trade secrets.

An IL formulation (i.e., by direct injection) of cGMP RBD drug substance, cGMP PV-10, is being developed as an autolytic immunotherapy drug product for solid tumor cancers.

IL PV-10 is also undergoing preclinical study for relapsed and refractory pediatric solid tumor cancers, such as neuroblastoma, Ewing sarcoma, rhabdomyosarcoma, and osteosarcoma.5,6

A topical formulation of cGMP RBD drug substance, PH-10, is being developed as a clinical-stage immuno-dermatology drug product for inflammatory dermatoses, such as atopic dermatitis and psoriasis. RBD can modulate multiple interleukin and interferon pathways and key cytokine disease drivers.7

Oral formulations of cGMP RBD are undergoing preclinical study for relapsed and refractory pediatric blood cancers, such as acute lymphocytic leukemia and acute myelomonocytic leukemia.8,9

Oral formulations of cGMP RBD are also undergoing preclinical study as prophylactic and therapeutic treatments for high-risk adult solid tumor cancers, such as head and neck, breast, pancreatic, liver, and colorectal cancers.

Different formulations of cGMP RBD are also undergoing preclinical study as potential treatments for multi-drug resistant (MDR) bacteria, such as Gram-negative bacteria.

Topical formulations of cGMP RBD are also undergoing preclinical study as potential treatments for diseases of the eye, such as infectious keratitis

Tumor Cell Lysosomes as the Seminal Cancer Drug Target

Lysosomes are the central organelles for intracellular degradation of biological materials, and nearly all types of eukaryotic cells have them. Discovered by Christian de Duve, MD in 1955, lysosomes are linked to several biological processes, including cell death and immune response. In 1959, de Duve described them as ‘suicide bags’ because their rupture causes cell death and tissue autolysis. He was awarded the Nobel Prize in 1974 for discovering and characterizing lysosomes, which are also linked to each of the three primary cell death pathways: apoptosis, autophagy, and necrosis.

Building on the Discovery, Exploration, and Characterization of Lysosomes

Cancer cells, particularly advanced cancer cells, are very dependent on effective lysosomal functioning.10 Cancer progression and metastasis are associated with lysosomal compartment changes11,12, which are closely correlated (among other things) with invasive growth, angiogenesis, and drug resistance13.

RBD selectively accumulates in the lysosomes of cancer cells upon contact, disrupting the lysosomes and causing the cells to die. Provectus2,14, external collaborators5, and other researchers15,16,17 have independently shown that RBD triggers each of the three primary cell death pathways: apoptosis, autophagy, and necrosis.

Cancer Cell Autolytic Death via RBD: RBD-induced autolytic cell death, or death by self-digestion, in Hepa1-6 murine hepatocellular carcinoma (HCC) cells can be viewed in this Provectus video of the process (ethidium homodimer 1 [ED-1] stains DNA, but is excluded from intact nuclei; lysosensor green [LSG] stains intact lysosomes; the video is provided in 30-second frames, with a duration of approximately one hour). Exposure to RBD triggers the disruption of lysosomes, followed by nucleus failure and autolytic cell death. Identical responses have been shown by the Company in HTB-133 human breast carcinoma (which can be viewed in this Provectus video of the process, with a duration of approximately two hours) and H69Ar human multidrug-resistant small cell lung carcinoma. Cancer cell autolytic cell death was reproduced by research collaborators in neuroblastoma cells to show that lysosomes are disrupted upon exposure to RBD.5

Tumor Autolytic Death via RBD: RBD causes acute autolytic destruction of injected tumors (via autolytic cell death), mediating the release of danger-associated molecular pattern molecules (DAMPs) and tumor antigens; release of these signaling factors may initiate an immunologic cascade where local response by the innate immune system may facilitate systemic anti-tumor immunity by the adaptive immune system. The DAMP release-mediated adaptive immune response activates lymphocytes, including CD8+ T cells, CD4+ T cells, and NKT cells, based on clinical and preclinical experience in multiple tumor types. Mediated immune signaling pathways may include an effect on STING, which plays an important role in innate immunity.9

Orphan Drug Designations (ODDs)

ODD status has been granted to RBD by the U.S. Food and Drug Administration for metastatic melanoma in 2006, hepatocellular carcinoma in 2011, neuroblastoma in 2018, and ocular melanoma (including uveal melanoma) in 2019.

Intellectual Property

Provectus’ IP includes a family of US and international (a number of countries in Asia, Europe, and North America) patents that protect the process by which cGMP RBD and related halogenated xanthenes are produced, avoiding the formation of previously unknown impurities that exist in commercial-grade rose bengal in uncontrolled amounts. The requirement to control these impurities is in accordance with International Council on Harmonisation (ICH) guidelines for the manufacturing of an injectable pharmaceutical. US patent numbers are 8,530,675, 9,273,022, and 9,422,260, with expirations ranging from 2030 to 2031.

The Company’s IP also includes a family of US and international (a number of countries in Asia, Europe, and North America) patents that protect the combination of RBD and CB (e.g., anti-CTLA-4, anti-PD-1, and anti-PD-L1 agents) for the treatment of a range of solid tumor cancers. US patent numbers are 9,107,887, 9,808,524, 9,839,688, and 10,471,144, with expirations ranging from 2032 to 2035; US patent application numbers include 20200138942 (i.e., 16/678,133), which has been allowed.

On June 4, 2021 Puma Biotechnology, Inc. (NASDAQ: PBYI), a biopharmaceutical company, presented results from the Phase III ExteNET trial assessing the impact of neratinib treatment duration on overall survival (OS) in patients with early stage HER2-positive breast cancer at the virtual 2021 ASCO (Free ASCO Whitepaper) Annual Meeting (Press release, Puma Biotechnology, JUN 4, 2021, View Source [SID1234583591]). The presentation, entitled "Association between treatment duration and overall survival in early-stage HER2+ breast cancer patients receiving extended adjuvant therapy with neratinib in the ExteNET trial," is included in the Breast Cancer—Local/Regional/Adjuvant Poster Session (#540).

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ExteNET was a multicenter, randomized, double-blind, Phase III trial of 2,840 HER2-positive early stage breast cancer patients who received neratinib after neoadjuvant and/or adjuvant therapy with chemotherapy and trastuzumab-based treatment. Patients were randomly assigned to one year of treatment with either oral neratinib 240 mg/day or placebo.

The poster presented by Professor Beverly Moy summarizes descriptive analyses evaluating the impact of duration of neratinib on clinical outcomes including invasive disease-free survival (iDFS) and distant disease-free survival (DDFS) at 5 years, and overall survival (OS). The analyses were performed in the intention-to-treat (ITT) population and subgroups of clinical interest including the HR+/≤1 year population (patients with hormone receptor-positive (HR+) disease who initiated neratinib within 1 year after prior trastuzumab) and within that subgroup, in the no pathologic complete response (pCR) group (patients from the HR+/≤1-year population with residual disease post-neoadjuvant therapy). Efficacy outcomes in patients who completed neratinib therapy were compared with placebo (all randomized patients). Completion of therapy was defined as patients who were on treatment for ≥ 11 months. Patients who ended neratinib therapy because of disease recurrence before 11 months were also considered with those who ‘completed therapy’ to reduce guarantee-time bias.

Among patients who completed ≥ 11 months of neratinib therapy, OS (median follow-up of 8.0 years) was improved versus placebo in each of the 3 groups. In the intention-to-treat (ITT) population, 872 of 1420 patients (61.4%) in the neratinib arm completed ≥ 11 months of treatment; OS rates were 92.2% vs 90.2% in the neratinib vs placebo arms, respectively, corresponding to a 2.0% improvement (HR 0.78; 95% confidence interval (CI) 0.58-1.04). In the HR+/≤1 year patient population, 402 of 670 patients (60%) in the neratinib arm completed ≥ 11 months of treatment; OS rates were 95.2% vs 89.4% in the neratinib vs placebo arms, respectively, corresponding to a 5.8% improvement (HR 0.49; 95% CI 0.29‒0.78). In the HR+/ <1 year, no pCR group, 92 of 131 patients (70.2%) in the neratinib group completed ≥ 11 months of treatment; OS rates were 95.4% vs 82.2% in the neratinib vs placebo arm, respectively, corresponding to a 13.2% improvement (HR 0.29; 95% CI 0.10–0.68).

Neratinib also numerically improved 5-year iDFS and DDFS outcomes versus placebo in all groups: 3.3% and 2.0%, respectively, in the ITT group of patients who completed therapy; 7.4% and 5.9%, respectively, in the HR+/≤1 year subgroup who completed therapy; and 11.9% and 10.9%, respectively, in the HR+/≤1 year no pCR subgroup who completed therapy.

Importantly, completion ≥ 11 months of therapy was associated with more pronounced improvements in all endpoints evaluated. In the ITT population, the HR for OS was reduced from 0.95 to 0.78 upon completion of therapy. In the HR+/≤1-year population, the HR for OS was reduced from 0.79 to 0.49 upon completion of therapy. In the HR+/≤1-year no pCR group, the HR for OS was reduced from 0.47 to 0.29 upon completion of therapy. Consistent improvements upon completion of therapy were also seen for iDFS and DDFS.

"These descriptive findings suggest that overall survival in patients with early stage HER2-positive breast cancer patients is improved upon completion of neratinib extended adjuvant therapy. This improvement trend was observed across all groups and reflected in the iDFS measurements as well, thereby showing that a complete course of neratinib in patients with early stage HER2-positive breast cancer who are at a high risk of relapse can be beneficial," said Beverly Moy, MD, MPH, Clinical Director of the Breast Oncology Program at Massachusetts General Hospital.

Alan H. Auerbach, Chief Executive Officer and President of Puma, added, "These data show that adherence to neratinib in the extended adjuvant setting lowers the risk of recurrence and improves overall survival. These findings are consistent with previously presented data and add to the growing body of evidence supporting the use of neratinib in HER2-positive early stage breast cancer."

About HER2-Positive Breast Cancer

Up to 20% of patients with breast cancer tumors over-express the HER2 protein (HER2-positive disease) and in the ExteNET study, 57% of patients were found to have tumors that were hormone-receptor positive. HER2-positive breast cancer is often more aggressive than other types of breast cancer, increasing the risk of disease progression and death. Although research has shown that trastuzumab can reduce the risk of early stage HER2-positive breast cancer recurring, up to 25% of patients treated with trastuzumab experience recurrence within 10 years, the majority of which are metastatic recurrences.

On June 4, 2021 SQZ Biotechnologies Company (NYSE: SQZ), focused on unlocking the full potential of cell therapies for multiple therapeutic areas, reported initial results from its ongoing Phase 1 clinical trial of SQZ-PBMC-HPV demonstrating that the investigational cell therapy is safe and well-tolerated and can stimulate immune responses in certain patients with advanced or metastatic Human Papillomavirus positive (HPV16+) tumors (Press release, SQZ Biotech, JUN 4, 2021, View Source [SID1234583627]). The trial also showed that the company’s clinical stage manufacturing process of its autologous cell therapy is fast and reliable. The monotherapy stage trial data of the company’s first Antigen Presenting Cell (APC) platform candidate was presented at the 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) annual meeting; poster presentation 2536.

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"Our vision is to make cell therapies that are safe and available with rapid turnaround times, allowing access to patients who need them," said Oliver Rosen, M.D., chief medical officer at SQZ Biotechnologies. "The company’s first-in-human data of a cell-based therapeutic vaccine are encouraging and an important first step towards validation of our directed immunity approach. Within this small trial of patients with very advanced disease, four patients who had progressed after multiple prior therapies achieved stable disease. These early outcomes, combined with encouraging safety data and fast clinical-scale manufacturing times, support our plans to initiate the trial’s safety combination phase with immune checkpoint inhibitors."

Safety & Tolerability

A primary outcome measure in the monotherapy dose escalation phase of the trial is safety and tolerability. Findings from the trial show that SQZ-PBMC-HPV was safe and well-tolerated at all tested dose levels with patients receiving 2 to 10 doses. No dose-limiting toxicities were observed.

"Overall, SQZ-PBMC-HPV has been safe and well tolerated by patients, even advanced patients as we have seen in this study," said study author Antonio Jimeno, M.D., Ph.D., Professor of Medicine, Oncology and Otolaryngology, University of Colorado School of Medicine, and Co-Leader, Development Therapeutics Program, University of Colorado Cancer Center. "I look forward to completing the single agent portion of the trial and advancing into the combinations of SQZ-PBMC-HPV with immunotherapies."

There were no grade 3 or higher treatment related serious adverse events (SAEs). In one patient, a grade 2 cytokine release syndrome and immune-related reaction was observed. A related grade 3 adverse event (AE, anemia) was observed in another patient.

Manufacturability

Manufacturing feasibility is a secondary outcome measure in the monotherapy phase of the trial. All patient batches were produced under current good manufacturing practice regulations, met specifications, and yielded multiple cryopreserved doses in less than 24 hours.

The findings show that doses of SQZ-PBMC-HPV were released and available for administration approximately one week from the time a patient’s cells were drawn. Antigen presentation was confirmed in all patient batches independent of individual patient medical history or prognostic score.

Patient Characteristics & Immune Response Biomarkers

The clinical trial enrolled patients with HPV16+ cancers progressing after unlimited prior lines of therapy. The 12 enrolled patients had very advanced disease:

Median number of prior cancer treatments was four with one patient having received seven prior treatments

Eleven patients previously treated with an immune checkpoint inhibitor (ICI)

Six of the 12 patients had a Royal Marsden Hospital (RMH) score of 2. (RMH scores range from 0-to-3, with scores of 2 and higher predicting poor prognosis and short life expectancy)

Despite the treatment refractory status of the enrolled patients, 4 out of 6 patients with RMH scores less than 2, reflecting less advanced disease, achieved stable disease as best overall response. Two of these patients showed an increase in CD8 tumor infiltrating lymphocytes (TILs), an important biomarker in immune-oncology therapy development.

The study authors highlighted two patients – Patients 2 and 7 detailed below – which suggested that less advanced patients with lower tumor burden, such as patient two, might have a higher likelihood of clinical benefit.

Patient 2: Enrolled 3-and-half years after diagnosis and had a best overall response of progressive disease with ICI therapy. The patient had an RMH score of 1 and low tumor burden. She achieved stable disease while on the SQZ-PBMC-HPV-101 trial and remained on study for over 10 months. Image analysis of the central tumor 28 days after the first dose showed a 2-fold increase in CD8 TILs on treatment compared to baseline

Patient 7: Enrolled 1 year after diagnosis and had a partial response with chemotherapy in combination with ICI therapy but then progressed. He achieved stable disease after treatment on the SQZ-PBMC-HPV-101 trial and remained on study for three months. Image analysis of the central tumor showed a 6-fold increase in CD8 TILs on treatment compared to baseline

The company is now actively enrolling patients in the last monotherapy highest-dose cohort of the Phase 1 trial. These results will inform the dosage approach for the combination therapy phase of the clinical trial with immune checkpoint inhibitors.

Poster Presentation Details

Title: Initial Results of a first-in-human, dose escalation study of a cell-based vaccine in HLA-A* 02+ patients with recurrent, locally advanced or metastatic HPV16+ solid tumors

First Author: Antonio Jimeno, M.D., Ph.D., University of Colorado Cancer Center

Abstract Number: 2536

Poster Session: Developmental Therapeutics — Immunotherapy

Date and Time: A copy of the poster is available on-demand via the ASCO (Free ASCO Whitepaper) virtual meeting website.

SQZ-PBMC-HPV-101 Trial Design

SQZ-PBMC-HPV is being evaluated in a Phase 1 clinical trial for the treatment of HPV16+ advanced or metastatic solid tumors. Patients must be positive for the human leukocyte antigen serotype HLA-A*02. The investigational candidate, which targets E6 and E7 oncoproteins, is being studied as a monotherapy and in combination with immuno-oncology agents. The study’s primary outcome measures in the monotherapy and combination phases of the trial include safety and tolerability. Antitumor activity is a secondary outcome measure in both the monotherapy and combination stages of the trial, and manufacturing feasibility is a secondary outcome measure in the monotherapy phase of the trial. The monotherapy phase of the study includes escalating dose cohorts with a DLT window of 28 days and the definition of a recommended phase 2 dose. The planned safety combination phase of the study will include SQZ-PBMC-HPV and checkpoint inhibitors that have previously received regulatory approval. DLT will be measured over 42 days in the safety combination phase.

About Human Papillomavirus Positive Cancers

Human papillomavirus (HPV) is one of the most common viruses worldwide and certain strains persist for many years leading to cancer. According to the Centers for Disease Control (CDC), in the United States HPV+ tumors represent 3% of all cancers in women and 2% of all cancers in men, resulting in over 39,000 new cases of HPV+ tumors every year. HPV infection is larger outside of the U.S., and according to the International Journal of Cancer HPV+ tumors account for 4.5% of all cancers worldwide, resulting in approximately 630,000 new cases every year. According to the CDC, HPV infection plays a significant role in the formation of more than 90% of anal and cervical cancers, and most cases of vaginal (75%), oropharyngeal (70%), vulval (70%) and penile (60%) cancers.