On September 10, 2022 Eisai reported that results from a post-hoc analysis of three randomized, pivotal, Phase 3 studies (EMBRACE trial/Study 305, Study 301, and Study 304) evaluating the efficacy of eribulin mesylate (marketed as HALAVEN) versus other chemotherapies (Treatment of Physician’s Choice [TPC], capecitabine, and vinorelbine, respectively) in patients living with metastatic breast cancer (mBC) whose tumors have low or no HER2 expression. These data were presented as a poster (Presentation: #259P) at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Annual Meeting (#ESMO22), held virtually and in-person in Paris, France from September 9-13, 2022 (Press release, Eisai, SEP 10, 2022, View Source [SID1234619385]).

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The HER2-low breast cancer subtype is a newly defined subset consisting of tumors that would have previously been considered HER2-negative based on an immunohistochemistry (IHC) assay and an in situ hybridization (ISH) assay. HER2-low tumors express low amounts of the HER2 protein, but not enough to be considered HER2-positive. HER2-low is defined as an IHC of 1+ or 2 with a negative ISH. Of the approximate 288,000 new cases of female breast cancer expected to be diagnosed in the U.S. in 2022, it is estimated that approximately 80-85% of patients would previously have been considered to have the HER2-negative subtype. Of those patients, about 60% would now be considered to have the HER2-low subtype.

"In this post-hoc analysis, the outcomes seen in mBC patients whose tumors are considered HER2-low are consistent with the results of the three pivotal Phase 3 clinical trials," said Dr. Takashi Owa, Chief Scientific Officer, Senior Vice President, Eisai Co., Ltd. "As the oncology community’s understanding of mBC continues to evolve, it’s important that we continue to evaluate the role of existing therapies in new contexts to contribute to the body of knowledge that is available to health care professionals."

Data from the Post-Hoc Analysis
The post-hoc analysis included data from three trials— eribulin vs. TPC (NCT00388726, EMBRACE trial/Study 305), eribulin vs. capecitabine (NCT00337103, Study 301), and eribulin vs. vinorelbine (NCT02225470, Study 304) in patients with locally recurrent or mBC who had prior lines of chemotherapy treatments (≤2 for Study 301; 2-5 for Study 304 and EMBRACE Trial/Study 305) including an anthracycline and a taxane. A total of 1,589 eligible patients were enrolled in the EMBRACE trial/Study 305, Study 301, and Study 304, and baseline characteristics were generally balanced between treatment arms in all studies.

Median overall survival (OS), median progression free survival (PFS) and objective response rate (ORR) were analyzed. PFS and ORR were measured per Response Evaluation Criteria in Solid Tumors Version (RECIST) (v1.0 for EMBRACE trial/Study 305 and Study 301; v1.1 for Study 304) by independent imaging review. ORR was measured in evaluable patients (EMBRACE trial/Study 305) and in the intent-to-treat population (Study 301 and Study 304).

In the post-hoc analysis, OS, PFS, and ORR among patients with HER2-low or HER2-negative status were generally similar to those of the eribulin treatment arms overall in each of the EMBRACE trial/Study 305, Study 301 and Study 304. Efficacy results for patients with HER2-low and HER2-negative status across all three studies are summarized in the table below:

*CI: Confidence Interval, HR: Hazard Ratio, NE: Not Evaluable

About Metastatic Breast Cancer
Metastatic breast cancer (mBC) is an advanced stage of the disease that occurs when cancer spreads beyond the breast to other parts of the body. It is estimated there were more than 2,261,000 new cases of breast cancer and more than 684,000 deaths from the disease globally in 2020. In 2022, it is estimated that approximately 288,000 women will be diagnosed with breast cancer in the United States and over 43,000 women will die from the disease. It is estimated that 30% of people with early-stage breast cancers will go on to develop metastatic disease, and approximately 6% of women with breast cancer will have metastatic disease at the time of diagnosis. Metastatic breast cancer has a poor prognosis compared to non-metastatic breast cancer. The estimated 5-year relative survival rate for women with mBC is 28%.

About HALAVEN (eribulin mesylate) Injection
HALAVEN (eribulin mesylate) Injection is indicated for the treatment of patients with metastatic breast cancer (mBC) who have previously received at least 2 chemotherapeutic regimens for the treatment of metastatic disease. Prior therapy should have included an anthracycline and a taxane in either the adjuvant or metastatic setting.

Eribulin is a microtubule dynamics inhibitor in the halichondrin class with a novel mechanism of action, developed in-house by Eisai. Structurally, eribulin is a simplified and synthetically produced version of halichondrin B, a natural product isolated from the marine sponge Halichondria okadai. Eribulin is believed to work by inhibiting the growth phase of microtubule dynamics which prevents cell division. In addition, non-clinical studies showed eribulin’s unique actions in the tumor microenvironment such as an increase in vascular perfusion and permeability in tumor cores, promotion of the epithelial state, decrease in capacity of breast cancer cells to migrate, etc.

Important Safety Information
Warnings and Precautions
Neutropenia: Severe neutropenia (ANC <500/mm3) lasting >1 week occurred in 12% of patients with mBC. Febrile neutropenia occurred in 5% of patients with mBC and 2 patients (0.4%) died from complications. Patients with mBC with elevated liver enzymes >3 × ULN and bilirubin >1.5 × ULN experienced a higher incidence of Grade 4 neutropenia and febrile neutropenia than patients with normal levels. Monitor complete blood cell counts prior to each dose, and increase the frequency of monitoring in patients who develop Grade 3 or 4 cytopenias. Delay administration and reduce subsequent doses in patients who experience febrile neutropenia or Grade 4 neutropenia lasting >7 days.

Peripheral Neuropathy: Grade 3 peripheral neuropathy occurred in 8% of patients with mBC (Grade 4=0.4%) and 22% developed a new or worsening neuropathy that had not recovered within a median follow-up duration of 269 days (range 25-662 days). Neuropathy lasting >1 year occurred in 5% of patients with mBC. Patients should be monitored for signs of peripheral motor and sensory neuropathy. Withhold HALAVEN in patients who experience Grade 3 or 4 peripheral neuropathy until resolution to Grade 2 or less.

Embryo-Fetal Toxicity: HALAVEN can cause fetal harm when administered to a pregnant woman. Advise females of reproductive potential to use effective contraception during treatment with HALAVEN and for at least 2 weeks following the final dose. Advise males with female partners of reproductive potential to use effective contraception during treatment with HALAVEN and for 3.5 months following the final dose.

QT Prolongation: Monitor for prolonged QT intervals in patients with congestive heart failure, bradyarrhythmias, drugs known to prolong the QT interval, and electrolyte abnormalities. Correct hypokalemia or hypomagnesemia prior to initiating HALAVEN and monitor these electrolytes periodically during therapy. Avoid in patients with congenital long QT syndrome.

Adverse Reactions
In patients with mBC receiving HALAVEN, the most common adverse reactions (≥25%) were neutropenia (82%), anemia (58%), asthenia/fatigue (54%), alopecia (45%), peripheral neuropathy (35%), nausea (35%), and constipation (25%). Febrile neutropenia (4%) and neutropenia (2%) were the most common serious adverse reactions. The most common adverse reaction resulting in discontinuation was peripheral neuropathy (5%).

Use in Specific Populations
Lactation: Because of the potential for serious adverse reactions in breastfed infants from eribulin mesylate, advise women not to breastfeed during treatment with HALAVEN and for 2 weeks after the final dose.

Hepatic and Renal Impairment: A reduction in starting dose is recommended for patients with mild or moderate hepatic impairment and/or moderate or severe renal impairment.

For more information about HALAVEN, click here for the full Prescribing Information.
HALAVEN is a registered trademark used by Eisai Inc. under license from Eisai R&D Management Co., Ltd.

On September 10, 2022 CatalYm, reported that data from its first-in-human GDFather-1 trial (GDF-15-neutralizing antibody-mediated human effector cell relocation) at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2022 held in Paris, France (Press release, Catalym, SEP 10, 2022, View Source [SID1234619379]). The clinical trial evaluated the GDF-15 neutralizing antibody visugromab (previously known as CTL-002), in combination with anti-PD-1 therapy nivolumab in advanced-stage solid tumor patients who had exhausted all previous lines of treatment and had relapsed on or were refractory to prior anti-PD-1/PD-L1 treatment. The data presented during today’s oral "Investigational Immunotherapy" session showed an excellent safety and tolerability profile as well as significant tumor regression at therapeutic doses and lasting response levels in a patient population with an otherwise poor prognosis.

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The presentation at ESMO (Free ESMO Whitepaper) by International Coordinating Investigator Prof. Dr. Ignacio Melero Bermejo, MD, Co-Director of Immunology and Immunotherapy (CIMA) at the Universidad de Navarra, Pamplona/Spain builds on the interim analyses announced in October and November of 2021. The current analysis reconfirms the excellent safety and tolerability profile with no dose-limiting toxicity observed and no grade 4 or 5 treatment emergent adverse events (TEAE). Pharmacokinetics and pharmacodynamic data indicated complete neutralization of GDF-15 with no signs for formation of anti-drug antibodies that could affect efficacy or safety. Furthermore, triple tumor biopsy analyses revealed a tumor-selective increase in CD8+ and CD4+ T cell infiltration following visugromab monotherapy treatment in the majority of patients investigated which continued under the addition of nivolumab. In addition, the majority of patients analyzed showed an increase in T cell proliferation and Granzyme B expression in the tumor microenvironment with both monotherapy and combination, reflective of the induction of an adaptive immune response.

"These mature Phase 1 trial data clearly demonstrate the significant clinical potential of visugromab in a highly refractory solid tumor patient population. Neutralizing GDF-15 in last-line tumor patients that also have failed prior anti-PD-1/PD-L1 therapy may offer a new and promising treatment regimen for patients that have exhausted all other options," said Prof. Dr. Eugen Leo, Chief Medical Officer at CatalYm. "The outcome of the pharmacodynamic and biomarker analyses is very promising as it not only provides a robust proof-of-mechanism for visugromab at this early stage of development, but also identified valuable biomarkers of interest that can support future responder-patient selection strategies."

Dr. Phil L’Huillier, Chief Executive Officer at CatalYm added: "Today’s results demonstrate the progress we have made in executing on our goal of providing novel treatment options by targeting GDF-15 to overcome the immunosuppression challenges seen in GDF-15 expressing tumors. I am grateful to the patients and clinicians participating in the trial and my colleagues at CatalYm, who enabled the delivery of our clinical phase 1 development program in solid tumor indications ahead of time. Following these excellent results that demonstrated active drug properties, we launched a broad multi-arm Phase 2 development program (GDFATHER-2) in early 2022 and anticipate sharing additional updates in the near future."

At data cut-off, 6 out of 18 patients on dose levels three to five (DL3-5) in combination with nivolumab experienced significant clinical benefit with overall tumor regression rates of 22% (for DL3-5) and 25% (for DL4-5) and several partial remission and long-term stable disease. Three out of the six patients (one with cancer of unknown primary origin, one with mesothelioma, one with hepatocellular cancer) achieved a confirmed partial response (PR): one continuing currently up to and beyond 12 months of treatment, together with a long-term stable disease patient. These data demonstrate an encouraging clinical benefit at higher dose levels in this highly refractory, last-line patient population. The PRs occurred in patients that were in fourth, fifth and seventh line of treatment.

In addition, potential predictive biomarkers were identified that may allow selection of optimal target population for visugromab treatment. When applying these biomarkers retrospectively (present in roughly 1/3 of all last-line patients investigated), a PR rate of up to 50% and a Clinical Benefit Rate > 65% would have been achieved. A confirmatory clinical exploration of these findings is in preparation.

Based on the promising results the company has already initiated the Phase 2 GDFATHER-2 study earlier this year. The on-going study includes different cohorts, representing several main tumor types of interest to further evaluate clinical efficacy as well as safety, pharmacokinetics, and pharmacodynamics including broad biomarker evaluations. The phase 2 program will enroll up to 162 patients at clinical trial sites in Spain, Switzerland and Germany. Early data readouts are expected to become available mid next year.

On September 10, 2022 Exai Bio, a next-generation liquid biopsy company, and researchers at UCSF reported that data from a new study in a poster entitled "Serum-based colorectal cancer detection using orphan noncoding RNAs" at the 2022 European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) meeting (Press release, Exai Bio, SEP 10, 2022, View Source [SID1234619378]). This case-control study of 191 subjects demonstrated that Exai’s novel, RNA-based platform accurately predicted colorectal cancer (CRC) cases versus non-cancer controls, both overall and across the full ranges of cancer stages and categories of tumor size/extent.

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Exai Bio’s technology is based on using cell-free RNA sequencing to identify a novel class of cancer-associated small non-coding RNAs, termed orphan non-coding RNAs (oncRNAs). Exai has created a proprietary library of >250,000 oncRNAs found in several types of cancer. Because oncRNAs can be actively secreted by cancer cells, they are readily detectable in the blood of cancer patients and are largely absent in healthy individuals, making them potentially robust biomarkers with high sensitivity and specificity. These features give the Exai Bio RNA-based platform — which uses artificial intelligence (AI) to identify cancer-specific patterns among thousands of oncRNAs — several scientific and practical advantages over tests that use circulating tumor-derived DNA in mutational, epigenomic, or fragmentomic analyses.

In the present poster, the Exai oncRNA-based model, which used machine learning, predicted CRC with a high overall sensitivity of 90.6% at 90% specificity. Predictions were also accurate for stage I cancer (92% sensitivity) and for the lowest categories of tumor size/extent, T1/T2 (92.3% sensitivity), indicating that even the earliest stage cancers and smallest tumors were detectable. Exai Bio is thus positioned to improve patient care by developing a variety of liquid biopsy blood tests for CRC, including for early detection and monitoring of residual disease or recurrence.

Patrick Arensdorf, Chief Executive Officer of Exai Bio, commented, "We are truly excited about these findings. Exai Bio is working to fulfill unmet needs that exist despite recent advances in liquid biopsy testing. This work demonstrates that Exai Bio can measure novel biomarkers in blood-derived samples to accurately predict colorectal cancer, including the earliest-stage and smallest tumors. By achieving greater than 90% sensitivity at 90% specificity, we exceeded the sensitivity hurdle in the published CMS National Coverage Determination for blood-based biomarker tests in CRC screening1. Moreover, the oncRNA-based liquid biopsy technology will be compatible with standard sample requirements enabling easy integration into conventional clinical workflows. These results build on our earlier study in breast cancer and validate the applicability of cell-free RNA methods in yet another tumor type."

NCD for Colorectal Cancer Screening Test (210.3). Medicare Coverage Decision database: Screening for Colorectal Cancer biomarker-based test: CAG-00454N decision memo 01/19/2021; cms.gov.
Details of the ESMO (Free ESMO Whitepaper) 2022 eposter presentation:
Title: Serum-based colorectal cancer detection using orphan noncoding RNAs
Abstract category: Biomarkers (agnostic)
Abstract number: 4635
Authors: Hani Goodarzi, Jeffrey Wang, Oluwadamilare I. Afolabi, Lisa Fish, Helen Li, Kimberly H. Chau, Patrick Arensdorf, Fereydoun Hormozdiari, Babak Alipanahi

Posters will be available on-demand on the EMSO website for attendees (www.emso.org) beginning at 12:00 PM CEST on Friday, September 9, 2022 until Tuesday, September 13, 2022 Upon release at ESMO (Free ESMO Whitepaper), the poster will be accessible on the publications page of the Exai Bio website.

On September 10, 2022 ImCheck Therapeutics reported that promising updated safety and patient response data from the completed dose escalation combination cohort of its ongoing EVICTION clinical trial during an oral session at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress currently being held in Paris, France (Press release, ImCheck Therapeutics, SEP 10, 2022, View Source [SID1234619373]). EVICTION is an open-label Phase I/IIa study evaluating ImCheck’s lead antibody ICT01 as a monotherapy in both solid tumor and hematological cancers, and in combination with pembrolizumab in solid tumors.

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Results from the Phase I dose-escalation, combination cohorts (n=40 across 6 dose levels) demonstrated that treatment with ICT01 plus pembrolizumab induced disease control in 42% of melanoma (5/12), 22% of non-small-cell lung carcinoma (4/18), 22% of bladder cancer (2/9) patients and in 1 head and neck squamous cell carcinoma (HNSCC) patient, (1/1) as determined by RECIST1.1 criteria. All patients treated had previously failed at least one checkpoint inhibitor (CPI) regimen, which underscores the potential of ICT01 combination therapy as a novel option for relapsed/refractory patients post-CPI treatment, which remains a significant unmet medical need. Two partial responses were achieved in melanoma patients who reached follow-up beyond 6 and 16 months, with the latter patient also achieving a durable complete regression of a brain metastasis from 6 months onward. The broad antitumor response data suggest that higher baseline circulating γ9δ2 T cell levels correlate with better treatment outcomes. This supports the planned patient enrichment strategy utilizing lower baseline γ9δ2 T cell counts, as compared to ICT01 monotherapy, for eligibility in the upcoming Phase IIa combination groups of patients with CPI-refractory melanoma, chemotherapy-resistant bladder cancer, or CPI-refractory HNSCC.

"The data presented today demonstrate that the complementary mechanisms of action for ICT01 and pembrolizumab alter the tumor microenvironment to generate clinical responses against multiple CPI-resistant solid tumors," commented Paul Frohna, MD, PhD, Chief Medical Officer at ImCheck Therapeutics. "It is encouraging to see a continued good safety profile for ICT01 in the combination setting in addition to robust activation of γ9δ2 T cells that promote tumor infiltration of CD8 and NK cells, which can be fully unleashed to attack the cancerous cells by concomitant PD-1 blockade."

Pierre d’Epenoux, Chief Executive Officer of ImCheck Therapeutics added: "With these positive data, we further substantiate the potential of ICT01 as a novel, differentiated therapeutic approach for a broad population of cancer patients. We feel confident that we have achieved our goals for the first part of the EVICTION trial, both in monotherapy with cohort expansion already underway and in combination with pembrolizumab. We eagerly anticipate exciting clinical efficacy results from the Phase IIa next year."

The oral presentation, titled "The Combination of ICT01, a γ9δ2 T cell-activating mAb, plus Pembrolizumab Induces a Broad Antitumor Immune Response and Disease Control in Patients with CPI-Failure Melanoma, NSCLC and Bladder Cancer: EVICTION Trial", was given by Dr. Stéphane Champiat, lead study investigator of the EVICTION trial at the Gustave Roussy Cancer Center, Paris, France. The data was presented during the investigational immunotherapy session from 14:45 to 16:15 CEST on Saturday September 10, 2022.

About the EVICTION Trial
EVICTION is a first-in-human, dose escalation (Part 1) and cohort expansion (Part 2) clinical trial of ICT01 in patients with various advanced relapsed or refractory solid or hematologic cancers that have exhausted standard of care treatment options. Part 1 is a basket trial designed to characterize the preliminary safety, tolerability, and pharmacodynamic activity of ICT01 as monotherapy (Group A: solid tumors; Group B: hematologic tumors) and in combination with pembrolizumab (Group C: solid tumors). Group A includes bladder, breast, colorectal, gastric, melanoma, ovarian, prostate, and pancreatic cancer patients, Group B includes acute myeloid leukemia, acute lymphocytic leukemia, follicular lymphoma, and diffuse large B cell lymphoma patients, and Group C includes bladder, head and neck squamous cell carcinoma, melanoma, and non-small cell lung cancer patients. Basket trials are a clinical trial design that allows new drugs to be tested rapidly in a range of indications, providing initial data on multiple parameters that can contribute to an accelerated development timeline. Part 2 of the trial is a Phase II cohort expansion study in selected indications as both monotherapy and in combination. First indications selected for the Phase II monotherapy expansion cohorts are relapsed/refractory ovarian cancer and metastatic castrate-resistant prostate cancer. More information on the EVICTION trial can be found at clinicaltrials.gov (NCT04243499). A second clinical trial, EVICTION-2, evaluating the combination of ICT01 plus low dose subcutaneous IL-2 to selectively expand the number of γ9δ2 T cells in patients with solid tumors (prostate, pancreatic, ovarian, or colorectal cancer) is also ongoing (NCT05307874).

About ICT01
ICT01 is a humanized, anti-BTN3A (also known as CD277) monoclonal antibody that selectively activates γ9δ2 T cells, which are part of the innate immune system that is responsible for immunosurveillance of malignancy and infections. The 3 isoforms of BTN3A targeted by ICT01 are overexpressed on a number of solid tumors (e.g., bladder, colorectal, melanoma, ovarian, pancreatic, lung) and hematologic cancers (e.g., leukemia & lymphoma) and also expressed on the surface of innate (e.g., γδ T cells and NK cells) and adaptive immune cells (T cells and B cells). BTN3A is essential for the activation of the anti-tumor immune response of γ9δ2 T cells.

As demonstrated in EVICTION data presented at past AACR (Free AACR Whitepaper), EMSO and SITC (Free SITC Whitepaper) conferences, ICT01 selectively activates circulating γ9δ2 T cells that leads to migration of γ9δ2 T cells out of the circulation and into target tissue (e.g., tumors), while also activating the tumor-resident γ9δ2 T cells to directly kill malignant cells, which is accompanied by secretion of two key inflammatory cytokines, IFNγ and TNFα, that contribute to the expansion of the anti-tumor immune response. ICT01 has been shown to have anti-tumor activity against a range of cancers in in vitro and in vivo tumor models.

On September 10, 2022 Cardiff Oncology, Inc. ( Nasdaq: CRDF), a clinical-stage biotechnology company leveraging PLK1 inhibition to develop novel therapies across a range of cancers, reported new preclinical and clinical data from its program in KRAS-mutated mCRC (Press release, Cardiff Oncology, SEP 10, 2022, View Source [SID1234619372]). The data are featured in two posters being presented at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2022, which is taking place at the Paris Expo Porte de Versailles in Paris, France, and virtually.

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Poster 397P: Early Decreases in KRAS Mutant Allele Frequency (MAF) Predict Clinical Benefit to the PLK1 Inhibitor Onvansertib in Combination with FOLFIRI/bev in 2L Treatment of Metastatic Colorectal Carcinoma (mCRC)

Poster 397P includes updated data (data cut-off date: July 25, 2022), as well as the results of correlative biomarker analyses from a Phase 1b/2 clinical trial of onvansertib plus FOLFIRI/bevacizumab in second-line KRAS-mutated mCRC. Measures of clinical response were compared between subsets of patients defined as KRAS responders or non-responders. KRAS responders were defined as patients with a ≥90% decrease in KRAS mutant allele frequency (MAF) in circulating tumor DNA (ctDNA) after one treatment cycle.

"The data from this trial show onvansertib plus FOLFIRI and bevacizumab outperforming historical controls on multiple key endpoints and are highly encouraging," said Heinz-Josef Lenz, MD, FACP, professor of medicine at USC Norris Comprehensive Cancer Center and the trial’s principal investigator. "They suggest trial participants with various KRAS mutations experience durable clinical benefits and that the onvansertib-FOLFIRI combination is avoiding the mechanisms that typically drive rapid acquired resistance to the standard-of-care (SoC). This highlights onvansertib’s potential to fill a crucial gap in mCRC’s therapeutic paradigm, as there are currently limited options available for second line patients. In addition, the significant increases between response rates and progression-free survival in KRAS responders point to changes in MAF as a potential blood-based biomarker that could aid in treatment decisions."

Key data and conclusions presented in the poster include:

Overall response rate (ORR) and median progression-free survival (mPFS) reported in Phase 1b/2 trial substantially exceed those reported in historical control trials

ORR across all evaluable patients was 35%, with 17 of 48 evaluable patients achieving an objective response and responses have been observed across multiple KRAS variants
Median duration of response (mDoR) across all evaluable patients was 11.7 months (95% confidence interval (CI): 8.9 – not reached)
mPFS across all evaluable patients was 9.3 months (95% CI: 7.6 – 13.5)
Historical control trials of different drug combinations, including the standard-of-care (SOC) of FOLFIRI with bevacizumab, in similar patient populations have shown ORR and mPFS of 5 – 13% and ~4.5 – 5.7 months, respectively1-4
KRAS responders showed significantly greater ORR and mPFS compared to non-responders

ORR in KRAS responders vs. KRAS non-responders: 63.6% (14/22) vs. 8.7% (2/23) (p = 0.00014)
mPFS in KRAS responders vs. KRAS non-responders: 12.6 months vs. 6.0 months (p=0.019)
Poster 366P: The PLK1 Inhibitor Onvansertib Overcomes Irinotecan Resistance in RAS-mutated Metastatic Colorectal Cancer (mCRC) In Vivo and in Patients

Poster 366P includes findings (as of August 5, 2022) from Cardiff Oncology’s EAP of onvansertib in KRAS-mutated mCRC, as well as data from murine studies evaluating onvansertib in combination with irinotecan in 6 PDX models of irinotecan-resistant, RAS-mutated CRC. Clinical findings reported in the Expanded Access Program (EAP) were compared between KRAS responders and non-responders. To enroll in the EAP, a patient must have been ineligible for the Phase 1b/2 clinical trial having received prior treatment with irinotecan or failed or progressed on multiple prior lines of standard-of-care therapy. EAP patients are treated with the same treatment regimen (onvansertib 15 mg/m2 plus FOLFIRI and bevacizumab) and dosing schedule as patients in the Phase 1b/2 clinical trial.

Scott Kopetz, MD, PhD, FACP, professor, Department of Gastrointestinal Medical Oncology, Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center commented, "Currently available third-line or later treatment options for patients are severely limited, due in large part to the high prevalence of tumors that show resistance to irinotecan. Based on the findings being presented at ESMO (Free ESMO Whitepaper), combining onvansertib with the current SOC appears to be an innovative strategy that can overcome irinotecan resistance and address a broad and pressing unmet need. This hypothesis is further supported by onvansertib’s mechanism of action, which targets DNA damage repair pathways underlying resistance to irinotecan and other chemotherapeutic agents."

Key findings and conclusions presented in the poster include:

EAP patients with prior irinotecan treatment (43 out of a total of 51 EAP patients) showed clinical benefit following treatment with onvansertib plus FOLFIRI/bevacizumab

mPFS was 4.04 months (95% CI: 2.96 – 8.38); 6-month PFS rate was 37.3% (95% CI: 24.9 – 55.8)
Of EAP patients with prior irinotecan treatment, KRAS responders had significantly longer PFS compared to non-responders.

mPFS in KRAS responders vs. KRAS non-responders: 11.18 months vs. 3.25 months (p=0.0014)
The combination of onvansertib and irinotecan showed significantly greater anti-tumor activity compared to onvansertib monotherapy in 5 of 6 tested PDX models of irinotecan-resistant, RAS-mutated CRC.

The ESMO (Free ESMO Whitepaper) posters are currently available for viewing on the congress’s virtual platform and will also be presented by Drs. Lenz and Kopetz during Poster Sessions 8 and 7, respectively, on September 11, 2022. Following the congress, the posters will be available on the "Scientific Presentations" section of the Cardiff Oncology website at View Source

Clinical and Corporate Update Conference Call and Webcast
Cardiff Oncology will host a webcast and conference call to provide a clinical and corporate update to the investment community on Monday, September 12, 2022 at 4:30 PM ET. The event will feature discussions on the planned development pathway for onvansertib in KRAS-mutated metastatic colorectal cancer and updates on other development programs. In addition, company management will provide data updates from ongoing clinical trials. To access the call, please dial 1-877-407-9208 (domestic) or 1-201-493-6784 (international) and refer to conference ID 13731618. The conference call will also be webcast live and a link to the webcast can be accessed here. A replay of the webcast will be available by visiting the "Events" section of the Cardiff Oncology website after its conclusion.

About the Phase 1b/2 Trial of Onvansertib in the Second-Line Treatment of KRAS-mutated mCRC
This is a multi-center, single-arm, Phase 1b/2 trial of onvansertib in combination with standard-of-care FOLFIRI and Avastin (bevacizumab) to evaluate the safety and preliminary efficacy of the combination regimen in the second-line treatment of patients with KRAS-mutated mCRC. The trial, A Phase 1b/2 Study of Onvansertib (PCM-075) in Combination with FOLFIRI and Bevacizumab for Second–Line Treatment of Metastatic Colorectal Cancer in Patients with a KRAS Mutation, is enrolling patients with histologically confirmed metastatic and unresectable colorectal carcinoma harboring a KRAS mutation. Patients must also have experienced disease progression or treatment intolerance to first-line treatment with fluoropyrimidine and oxaliplatin (FOLFOX or CapeOx) with or without bevacizumab to be eligible. The trial is being conducted at the following cancer centers across the U.S.: USC Norris Comprehensive Cancer Center, The Mayo Clinic (Arizona, Rochester, and Jacksonville), Kansas University Medical Center (KUMC), CARTI Cancer Center and Inova Schar Cancer Institute. For more information on the trial, please visit NCT03829410.

About the EAP for Onvansertib in KRAS-mutated mCRC
Sometimes called "compassionate use", expanded access is a potential pathway for a patient with a serious or life-threatening disease to gain access to an investigational drug for treatment outside of a clinical trial, particularly when no comparable or satisfactory alternative therapy options are available. The Cardiff Oncology EAP in KRAS-mutated mCRC is using the same combination treatment regimen (onvansertib 15 mg/m2 + FOLFIRI and bevacizumab) and dosing schedule as the ongoing Phase 1b/2 clinical trial and is intended for patients that have progressed on prior therapy and do not meet the second line eligibility criteria for enrollment in the clinical trial. The program has reached capacity and is no longer open to enrollment.