On April 27, 2020 Alligator Bioscience (Nasdaq Stockholm: ATORX), reported that the company presents the status of the ongoing Phase I clinical trial with the bispecific drug candidate ATOR-1015 developed as tumor-directed therapy for metastatic cancer (Press release, Alligator Bioscience, APR 27, 2020, View Source [SID1234556607]). The presentation will take place at the AACR (Free AACR Whitepaper) (American Association for Cancer Research) Annual Meeting, which this year is being held digital for the first time.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

This far, doses of 400 mg (about 6 mg/kg) have been evaluated in the ongoing study and the current dosing is 600 mg (about 10 mg/kg). 18 patients with varying cancer forms (colon cancer, eye melanoma, pancreatic cancer, ovarian cancer, gallbladder cancer, gastric cancer and skin cancer) have been treated and evaluated in terms of safety. ATOR-1015 has so far been well tolerated.

"We are very proud and happy that our study has been selected for presentation. The promising results so far demonstrate that ATOR-1015 can be administered safely. ATOR-1015 has the potential to be at least as effective as today’s available treatment for these patients, but with significantly fewer side effects," said Per Norlén, CEO of Alligator Bioscience.

The adverse events in the study were generally mild and transient, all of grade 1 or 2 (on a scale of 1-5). The most common adverse events were infusion-related reactions (five patients). No serious immune-related or dose-limiting adverse events have been reported.

The presentation with the title "A first-in-human phase 1 study in patients with advanced and/or refractory solid malignancies to evaluate the safety of ATOR-1015, a CTLA-4 x OX40 bispecific antibody" will be held by Charlotte Russell, Chief Medical Officer at Alligator Bioscience. The presentation is available through the link below between 9:00 a.m. – 6:00 p.m. EDT (3 p.m.-12 a.m. CEST) today and will also be available on the company website www.alligatorbioscience.com. View Source!/9045/presentation/10644

About the ATOR-1015 Phase I study
The Phase I study with ATOR-1015 is a dose escalation study in patients with metastatic cancer (NCT03782467). The primary endpoint of the study is to investigate the safety and tolerability of ATOR-1015 and to determine the recommended dose for subsequent Phase II studies. The first patient was dosed in March 2019 and results are expected during the second half of 2020. Following the establishment of the maximum tolerable dose or recommended dose for Phase II, further clinical development of ATOR-1015 is planned, primarily for the treatment of metastatic skin cancer.

Due to the Covid-19 pandemic, most, but not all, participating clinics have made a temporary halt in the recruitment of new patients. Alligator Bioscience is in close dialogue with all parties in order to resume patient recruitment at full speed as soon as possible. The company follows the clinics’ decisions and evaluates appropriate measures to minimize any delays. At this stage, it is too early to estimate whether the slower recruitment will affect the timeline for 2020 and for the longer term.

About ATOR-1015
ATOR-1015, wholly owned by Alligator, is a bispecific CTLA-4 antibody developed as tumor targeted immunotherapy with increased capacity for killing regulatory T cells. ATOR-1015 binds to two different immune receptors – the checkpoint receptor CTLA-4 and the co-stimulatory receptor OX40. The immune activation is increased in areas where both target molecules are expressed at high levels, notably in the tumor microenvironment, which can lead to reduced side effects.

On April 27, 2020 Sutro Biopharma, Inc. (NASDAQ: STRO), a clinical-stage drug discovery, development and manufacturing company focused on the application of precise protein engineering and rational design to create next-generation oncology therapeutics, reported updated interim data regarding safety and anti-tumor activity results in heavily pre-treated patients with ovarian cancer from its on-going Phase 1 clinical trial (dose escalation phase) evaluating its folate receptor alpha (FolRα) antibody drug-conjugate (ADC) STRO-002 (Press release, Sutro Biopharma, APR 27, 2020, View Source [SID1234556606]). Sutro will host a conference call and live audio webcast on Monday, April 27, at 8 a.m. EDT to discuss the STRO-002 data.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"We designed STRO-002 to have a wider therapeutic window, with the potential for improved tumor control and better patient tolerability, than other FolRα targeted therapies," said Bill Newell, CEO of Sutro Biopharma. "The data we present today from this all-comers trial suggest that our optimally designed ADC can achieve these objectives. In 75% (15 of 20) of ovarian cancer patients at STRO-002 dose levels of 2.9 milligrams per kilogram (mpk) or higher, we saw in the initial post-baseline scans one partial response and 14 stable disease. This level of tumor control is typically very difficult to achieve in these patients who have been heavily pre-treated, with a median of five prior lines of other therapies, and who have such advanced disease. Equally encouraging are the data showing that 13 patients had a ≥50% reduction or normalization of CA-125, including six confirmed responses, six unconfirmed responses and one prolonged CA-125 normalization. Of these 13 patients, one patient is not yet evaluable under RECIST criteria. All of the other 12 patients (100%) have also achieved stable disease (confirmed or unconfirmed) or a confirmed partial response. With 89% of adverse events (AEs) reported to be grade 1 or 2, we believe the emerging safety profile reflects our optimized design approach."

The interim clinical data for STRO-002 in patients treated at dose levels of 2.9 mpk or higher include: one patient with an ongoing confirmed partial response (36 weeks); five patients with confirmed stable disease (three up to 18 weeks, two up to 27 weeks); and seven ongoing patients who have unconfirmed stable disease at the six-week assessment point.

STRO-002 was generally well-tolerated and was mostly associated with mild AEs. Eighty-nine percent (89%) of AEs were grade 1 or grade 2 and prophylactic corticosteroid eye drops have not been necessary. Grade 3 treatment emergent AEs included fatigue, neutropenia, arthralgia, diarrhea, peripheral neuropathy and myalgia, with the only grade 4 treatment emergent AE being neutropenia; all neutropenias were reversible within one week.

"The preliminary evidence of anti-tumor activity we observed is encouraging, particularly in this heavily pre-treated patient population," said Wendel Naumann, MD, gynecologic oncologist at Levine Cancer Institute and a principal investigator on the STRO-002 study. "With limited therapeutic options for these patients, we are excited to continue to advance this clinical program to further investigate its therapeutic potential."

"These data support Sutro’s continued development of targeted therapies for cancer patients and joins two other Sutro-developed and manufactured ADCs in clinical trials, including our BCMA-targeted ADC which is in a Phase 1 trial being conducted by our collaborator Bristol Myers Squibb," said Arturo Molina, MD, Sutro’s Chief Medical Officer. "It is extremely encouraging that we see this preliminary evidence of anti-tumor activity at this stage of development. As we advance STRO-002 in the clinic, we plan to share additional data on the efficacy and safety of STRO-002 by the end of 2020 and we look forward to the potential to bring a new treatment option to ovarian cancer patients."

Through April 20, 2020, the Phase 1 trial of STRO-002 has enrolled 30 patients with recurrent platinum resistant or refractory ovarian cancer, without regard to FolRα expression levels. A dose expansion phase of this trial is planned to commence in the second half of 2020. Although maximum tolerated dose (MTD) has not been reached, Sutro is continuing to actively explore the 5.2 mpk to 6.0 mpk dose levels as it seeks to determine the recommended Phase 2 dose.

The ongoing Phase 1, open-label, multicenter, dose escalation trial with dose expansion of STRO-002 is designed to identify the MTD, the recommended Phase 2 clinical dose and to evaluate the safety, tolerability, and preliminary anti-tumor activity of STRO-002 in adults with advanced epithelial ovarian cancer, including fallopian or primary peritoneal cancer, and endometrial cancer. This trial is registered with clinicaltrials.gov identifier NCT03748186. Sutro discovered, developed and manufactures STRO-002 using its proprietary XpressCF+ cell-free protein synthesis technology.

Conference Call Information:

To access the conference call and live audio webcast on Monday, April 27, at 8 a.m. EDT, please dial (833) 729-4781 (domestic) or (830) 213-7705 (international) and refer to conference ID 2699785.

The conference call will be webcast via the Investors page on the company’s website at ir.sutrobio.com. Approximately two hours following the live event, a webcast replay of the conference call will be available through the Company Presentation page of the Investor section of the company’s website at www.sutrobio.com for approximately 30 days.

Poster Presentation Details:

STRO-002-GM1, a First in Human, Phase 1 Study of STRO-002, an anti-Folate Receptor-alpha (FRα) Antibody Drug Conjugate (ADC), in Patients with Advanced Platinum-Resistant/Refractory Epithelial Ovarian Cancer (OC), including Fallopian Tube or Primary Peritoneal Cancers

Date & Time:

Monday, April 27, 2020, 9 a.m. to 6 p.m. EDT

Location:

The AACR (Free AACR Whitepaper) Virtual Meeting at aacr.org

Poster Number:

CT125

The poster will be accessible through the Clinical/Scientific Presentation and Publication Highlights page of the News section of the company’s website at www.sutrobio.com.

On April 27, 2020 I-SPY 2 TRIAL reported that results on April 27 at the clinical trial plenary session of the American Association for Cancer Research (AACR) (Free AACR Whitepaper) 2020 annual meeting, which showed that adding the immune checkpoint inhibitor durvalumab and the PARP inhibitor olaparib to standard of care pre-operative (neoadjuvant) chemotherapy improved outcomes for women with stage II/III, high-risk, HER2-Negative Breast Cancer (Press release, I-SPY 2 TRIAL, APR 27, 2020, View Source [SID1234556605]). Patients who received durvalumab + olaparib + paclitaxel (DOP) followed by doxorubicin/cyclophosphamide (AC), achieved complete eradication of their cancer from the breast and axillary lymph nodes at the time of surgery (i.e pathologic complete response) at a greater rate than patients treated with chemotherapy alone (37% versus 20%). This degree of response met the threshold for graduation, meaning that there is a greater than 85% predicted probability of success if this combination was tested against standard chemotherapy in a phase 3 trial of 300 neoadjuvant patients.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

I-SPY2 is a multicenter, phase 2 trial using response-adaptive randomization within molecular subtypes defined by receptor status and MammaPrint risk to evaluate novel agents as neoadjuvant therapy for breast cancer. I-SPY 2 evaluates drugs (or combination of drugs) in parallel with the goal of determining which drugs work best in various types of breast cancer. I-SPY 2 patients are given chemotherapy before surgery so that response to treatment can be assessed. The primary endpoint of the study is pathologic complete response (pCR). Patients who participated in this study had tumors ≥ 2.5 cm, were HER2-negative, and if the cancer was hormone receptor positive (HR+) had to be classified as MammaPrint high risk status. Lead investigator of the study arm, Dr. Lajos Pusztai, Professor of Medicine and Director of Breast Cancer Translational Research at Yale Cancer Center, presented the efficacy and biomarker results which showed the predicted probability of pCR for the overall HER2-negative group, (22% vs 37%) and by subtypes, in HER2-negative/ER-positive (14% vs 28%) and triple negative (TNBC) (27% vs 47%) breast cancer subtypes.

The investigators also evaluated proposed potential markers that could identify the subgroup of patients who selectively benefited from the inclusion of immune enhancing agents such as durvalumab and DNA damage response targeting agents such as olaparib. Among the HR+/HER2- cohort, the MammaPrint ultra-high group was the primary beneficiary of the combined therapy (pCR rates 64% with the combination versus 22% with chemotherapy alone). Specific gene expression signatures thought to be associated with response were prospectively identified and the following were found to be associated with higher pCR in the experimental arm among TNBC: low CD3/CD8 ratio; high Macrophage/T cell-MHC class II ratio, and high proliferation. The safety signals were not unexpected. Adverse events were consistent with known side effects of these drugs. Overall 11% of patients in durvalumab + olaparib arm experienced immune-related grade 3 adverse events vs 1.3% in the control arm. According to Dr. Pusztai, chaperone for this arm in the I-SPY 2 TRIAL, "These results provide further evidence for the clinical value of immunotherapy in early stage breast cancer and suggest new avenues for how to exploit these drugs in HR+ breast cancers."

As noted by I-SPY 2 principal investigator, Dr. Laura Esserman of the University of California San Francisco, "There is a consistent signal of improved response from immuno-oncology and DNA damage response targeted agents in the adaptive I-SPY 2 platform trial as well as other trials, which gives us confidence that these types of agents will have a place in improving outcomes for women with highest risk early breast cancer. "

AACR has selected these findings as newsworthy and will be highlight during an AACR (Free AACR Whitepaper) webcast with the meeting program chair Dr. Antoni Ribas and AACR (Free AACR Whitepaper) President Dr. Elaine Mardis.

On April 27, 2020 GRAIL, Inc., a healthcare company whose mission is to detect cancer early, reported that new data for its investigational multi-cancer early detection blood test will be presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Virtual Annual Meeting I (Press release, Grail, APR 27, 2020, View Source [SID1234556604]). These new data evaluate the performance of GRAIL’s test in symptomatic participants with suspicion of cancer.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Today, the majority of deadly cancers do not have guideline-recommended screening tests available, and as a result, most cancers are detected too late, after they have progressed to late stages when chances of survival are much lower. There is also a high unmet need for early detection in the diagnostic assessment of symptomatic patients who are being evaluated for cancer. GRAIL’s multi-cancer early detection technology can detect more than 50 cancers, with a very low false positive rate of less than one percent, through a single blood draw. When a cancer signal is detected, the test can also identify where the cancer is located in the body (the tissue of origin) with high accuracy. This technology could be particularly useful in directing a more efficient diagnostic workup in symptomatic patients who are being evaluated for cancer.

"We continue to make significant progress in the validation of our multi-cancer early detection blood test, and wanted to assess its potential to drive efficiencies in the diagnostic workup of patients who are showing symptoms," said Alex Aravanis, MD, PhD, Chief Scientific Officer and Head of R&D, and a co-founder of GRAIL. "These findings show that when our multi-cancer test detected a cancer signal, it also identified where in the body that cancer was located with high accuracy. This is critical information for healthcare providers, and demonstrates the feasibility of our test to potentially accelerate diagnosis in individuals with high suspicion of cancer by helping direct the diagnostic workup."

These new data represent a pre-specified sub-group from GRAIL’s foundational Circulating Cell-free Genome Atlas (CCGA) study, which included more than 15,000 participants with or without a diagnosis of cancer. In the sub-group analysis reported at AACR (Free AACR Whitepaper), participants being evaluated for suspicion of cancer were classified as clinically confirmed cancer (n=164 in training, n=75 in validation) or clinically confirmed non-cancer (n=49 in training, n=15 in validation). In the confirmed non-cancer group, all training and validation samples were correctly predicted as non-cancer, or 100% specificity.

In the validation set, detection across all stages in the confirmed cancer group was 46.7% (n=35/75; 95% confidence interval [CI]: 35.1-58.6%) at 100% specificity. When renal cancers — which were overrepresented and subject to poor detection at early stages due to low tumor cfDNA fraction — were not included, detection across stages was 59.3% (n=35/59; 95% CI: 45.7-71.9%). In stages II and above, detection was 78.9% (n=30/38; 95% CI: 62.7-90.4%), all at 100% specificity. Performance was consistent across training and validation sets.

For cancers where a signal was detected, the tissue of origin (TOO) was predicted in 93.9% (n=62/66) of samples in training, and 100% (n=35/35) in validation. Of those with a TOO result, accuracy was 85.5% (n=53/62; 95% CI: 74.2-93.1%) and 97.1% (n=34/35; 95% CI: 85.1-99.9%), respectively.

The data are being presented online by David D. Thiel, MD, Chair, Mayo Clinic Florida Department of Urology. The presentation slides will be available at View Source after the presentation.

AACR Presentation Details

Abstract CT291
Lincoln Nadauld, et al. The PATHFINDER Study: Assessment of the implementation of an investigational multi-cancer early detection test into clinical practice
Session VPO.CT07.03 – Phase III Trials in Progress: April 27, 2020: 9:00AM-6:00PM EDT

Abstract CT021
David D. Thiel, et al. Prediction of cancer and tissue of origin in individuals with suspicion of cancer using a cell-free DNA multi-cancer early detection test
Session VCTPL02 – Early Detection and ctDNA: April 28, 2020: 1:40PM-1:50PM EDT

About CCGA

The Circulating Cell-free Genome Atlas (CCGA) study is a prospectively designed, observational, longitudinal, case-control study that has completed enrollment of approximately 15,000 participants with and without cancer across 142 sites in the United States and Canada. CCGA is designed to characterize the landscape of genomic cancer signals in the blood, and to discover, train, and validate GRAIL’s multi-cancer early detection blood test through three pre-planned sub-studies. To learn more about CCGA, please visit www.grail.com.

About GRAIL’s Multi-Cancer Early Detection Test

GRAIL’s multi-cancer early detection test is designed to detect cancers in early stages, when the chance of survival is higher than if cancer is detected after symptoms appear. Clinical data have shown the ability of this technology to detect more than 50 cancer types with a very low false positive rate of less than one percent. GRAIL’s test was designed to minimize false positives in order to limit associated harms, including patient anxiety and unnecessary diagnostic workups. When a cancer signal is detected, the test has been able to identify where in the body the cancer is located with high accuracy, an important step to guiding diagnostic next steps and care.

GRAIL’s methylation-based technology preferentially targets the most informative regions of the genome and is designed to use its proprietary database and machine-learning algorithms to both detect the presence of cancer and identify the tumor’s tissue of origin. GRAIL believes its sequencing database of cancer and non-cancer methylation signatures is the largest of its kind.

On April 27, 2020 Verastem, Inc. (Nasdaq:VSTM) (also known as Verastem Oncology), a biopharmaceutical company committed to developing and commercializing new medicines for patients battling cancer, reported results from the ongoing investigator-initiated Phase 1 clinical study investigating VS-6766, its RAF/MEK inhibitor, in combination with defactinib, its FAK inhibitor, in patients with KRAS mutant advanced solid tumors (Press release, Verastem, APR 27, 2020, View Source [SID1234556603]). The data will be presented as a virtual poster today at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) 2020 Virtual Annual Meeting I.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

This ongoing study is an open label, dose escalation and expansion study. The expansion cohorts are currently ongoing in patients with advanced solid tumors, including low-grade serous ovarian cancer (LGSOC), KRAS mutant non-small cell lung cancer (NSCLC) and KRAS mutant colorectal cancer (CRC). In the LGSOC cohort, among the patients with KRAS mutant tumors (n=6), 4 patients responded, for an overall response rate (ORR) of 67%. Median time on treatment was 20.5 months. In the KRAS mutant NSCLC cohort (n=10), 1 patient achieved a partial response and 8 patients achieved disease control. In this cohort, 70% of patients continued on treatment at least 12 weeks and 30% of patients continued on treatment at least 24 weeks.

Based on an observation of higher response rates seen in patients with KRASG12V mutations in the investigator-initiated Phase 1 combination study, we conducted a combined analysis with data from the combination study and the prior single-agent study that utilized a twice-weekly dosing schedule of VS-67661 to get a more complete picture of activity in KRASG12V mutations. The subsequent, combined analysis (VS-6766 monotherapy and defactinib combination) showed a 57% ORR (4/7 patients); as a single agent (2/5 patients) and in combination with defactinib (2/2 patients) in KRASG12V mutant NSCLC. Similarly, the combined analysis showed a 60% ORR (3/5 patients); as a single agent (1/2 patients) and in combination with defactinib (2/3 patients) in KRASG12V mutant gynecologic cancers. These additional analyses were conducted by Verastem Oncology to understand the impact that various KRAS variants may have had on response to identify potential signals to pursue in future prospective studies. This additional analysis was not part of the AACR (Free AACR Whitepaper) 2020 poster presentation.

"Earlier research has demonstrated MEK inhibitors can cause upregulation of FAK in KRAS mutant tumors, which are notoriously difficult to treat and quite common across solid tumors. The combination of a RAF/MEK and FAK inhibitor can potentially overcome this challenge and opens up an exciting new pathway for treatment," stated Professor Udai Banerji, Professor of Molecular Cancer Pharmacology at The Institute of Cancer Research, London, and Honorary Consultant in Medical Oncology, MBBS, MD, DNB, PhD, FRCP at The Royal Marsden NHS Foundation Trust, London, and lead investigator of the clinical study. "We found that the combination of VS-6766 and defactinib in low-grade serous ovarian cancer (LGSOC) was well tolerated by the patients in the trial and shows promising clinical activity, including durable response that is associated with clinically meaningful benefit. The study continues to enroll additional patients into the ovarian, lung and colorectal expansion cohorts with additional responses seen in all cohorts."

"We are encouraged by these early response rates in KRAS mutant LGSOC and in KRASG12V mutant tumors as they underscore the significant potential of this novel approach in areas of high unmet medical need," said Brian Stuglik, Chief Executive Officer of Verastem Oncology. "The potential of the combination of VS-6766 and defactinib is rapidly evolving as we continue to gain more insights and analyze the data. We plan to initiate discussions with regulatory authorities as soon as possible to define a path forward, with the goal of commencing a registration-directed clinical trial during 2020."

Initial Results from the Phase 1 Study Investigating the Combination of VS-6766 and Defactinib in Patients with KRAS Mutant Cancers and Subsequent Analyses

The poster presentation describes safety and dose response data from the dose-escalation portion and expansion cohorts from an open-label, investigator-initiated Phase 1 study conducted in the United Kingdom assessing the combination of RAF/MEK and FAK inhibitor therapy in patients with LGSOC and KRAS mutant NSCLC. The study evaluated the combination of VS-6766 and defactinib. VS-6766 was administered using a twice-weekly dose escalation schedule and was administered 3 out of every 4 weeks. Defactinib was administered using a twice-daily dose escalation schedule, also 3 out of every 4 weeks. Dose levels were assessed in 3 cohorts: cohort 1 (VS-6766 3.2mg, defactinib 200mg); cohort 2a (VS-6766 4mg, defactinib 200mg); and cohort 2b (VS-6766 3.2mg, defactinib 400mg).

In the patients with LGSOC (n=8), the ORR was 50% (n=4). Among the patients with KRAS mutant LGSOC (n=6), the ORR was 67% (n=4). Of the 4 patients who have responded, 3 had a prior MEK inhibitor and as of November 2019 had been on study for a median of 20.5 months (range 7-23 months). In the patients with NSCLC (n=10), all of which had KRAS mutations, 1 patient achieved a partial response and 1 patient with a 22% tumor reduction still on treatment as of November 2019. Median time on treatment for this cohort was approximately 18 weeks.

Based on an observation of higher response rates seen in patients with KRASG12V mutations in the investigator-initiated Phase 1 combination study, we conducted a combined analysis with data from the combination study and the prior single-agent study that utilized a twice-weekly dosing schedule of VS-67661 to get a more complete picture of activity in KRASG12V mutations. The subsequent, combined analysis (VS-6766 monotherapy and defactinib combination) showed a 57% ORR (4/7 patients); as a single agent (2/5 patients) and in combination with defactinib (2/2 patients) in KRASG12V mutant NSCLC. Similarly, the combined analysis showed a 60% ORR (3/5 patients); as a single agent (1/2 patients) and in combination with defactinib (2/3 patients) in KRASG12V mutant gynecologic cancers. These additional analyses were conducted by Verastem Oncology to understand the impact that various KRAS variants may have had on response to identify potential signals to pursue in future prospective studies. This additional analysis was not part of the AACR (Free AACR Whitepaper) 2020 poster presentation.

The most common side effects seen in the Phase 1 study were rash, creatine kinase elevation, nausea, hyperbilirubinemia and diarrhea, most being NCI CTC Grade 1/2 and all were reversible. The recommended Phase 2 dose was determined to be cohort 1 (VS-6766 3.2mg, defactinib 200mg).

The preliminary data reported in the study suggest that a novel intermittent dosing schedule of RAF/MEK and FAK inhibitor combination therapy has promising clinical activity in patients with KRASmutant LGSOC and KRASG12V mutant NSCLC, including patients previously treated with a MEK inhibitor. Expansion cohorts remain ongoing.

Details for the AACR (Free AACR Whitepaper) 2020 Virtual Meeting I presentation are as follows:

Title: Phase 1 study of the combination of a RAF-MEK inhibitor CH5126766 (VS-6766) and FAK inhibitor defactinib in an intermittent dosing schedule with expansions in KRAS mutant cancers
Lead author: Udai Banerji, The Institute of Cancer Research and The Royal Marsden
Poster #: CT143
Session: VPO.CT01 – Phase I Clinical Trials
Date and Time: Monday, April 27, 2020; 9:00 a.m. to 6:00 p.m. ET
URL: View Source!/9045/presentation/10642

Conference Call and Webcast Information

The Verastem Oncology management team will host a conference call and webcast on Monday, April 27, 2020, at 8:00 AM ET to discuss the Phase 1 RAF/MEK/FAK combination data. The call can be accessed by dialing (877) 341-5660 (U.S. and Canada) or (315) 625-3226 (international), five minutes prior to the start of the call and providing the passcode 8390795.

The live, listen-only webcast of the conference call can be accessed by visiting the investors section of the Company’s website at www.verastem.com. A replay of the webcast will be archived on the Company’s website for 90 days following the call.

About VS-6766

VS-6766 (formerly known as CH5126766, CKI27 and RO5126766) is a unique inhibitor of the RAF/MEK signaling pathway. In contrast to other MEK inhibitors in development, VS-6766 blocks both MEK kinase activity and the ability of RAF to phosphorylate MEK. This unique mechanism allows VS-6766 to block MEK signaling without the compensatory activation of MEK that appears to limit the efficacy of other inhibitors. The combination of VS-6766 and the focal adhesion kinase (FAK) inhibitor defactinib is currently being investigated in an investigator-initiated Phase 1 dose escalation and expansion study. The expansion cohorts are currently ongoing in patients with KRAS mutant advanced solid tumors, including low grade serous ovarian cancer (LGSOC), non-small cell lung cancer (NSCLC) and colorectal cancer (CRC).2 The ongoing clinical study of the VS-6766/defactinib combination is supported by single-agent Phase 2 studies which investigated defactinib in KRAS mutant NSCLC3 and VS-6766 in KRAS mutant NSCLC and LGSOC.1

About Defactinib

Defactinib is an oral small molecule inhibitor of FAK and PYK2 that is currently being evaluated as a potential combination therapy for various solid tumors. The Company has received Orphan Drug designation for defactinib in ovarian cancer and mesothelioma in the US, EU and Australia. Preclinical research by Verastem Oncology scientists and collaborators at world-renowned research institutions has described the effect of FAK inhibition to enhance immune response by decreasing immuno-suppressive cells, increasing cytotoxic T cells, and reducing stromal density, which allows tumor-killing immune cells to enter the tumor.4,5 Additionally, in both preclinical and clinical studies, FAK activation has been shown to occur as a potential resistance mechanism in response to MEK inhibitor treatment, and synergy of a FAK inhibitor with a RAF/MEK inhibitor has been shown in several preclinical models. The combination of defactinib and VS-6766 is currently being investigated in an investigator-initiated Phase 1 dose escalation and expansion study. The expansion cohorts are currently ongoing in patients with KRAS mutant advanced solid tumors, including low grade serous ovarian cancer (LGSOC), non-small cell lung cancer (NSCLC) and colorectal cancer (CRC).2 The ongoing clinical study of the VS-6766/defactinib combination is supported by single-agent Phase 2 studies which investigated defactinib in KRAS mutant NSCLC3 and VS-6766 in KRAS mutant NSCLC and LGSOC.4 Defactinib is also in clinical testing in combination with pembrolizumab for treatment of patients with pancreatic cancer, NSCLC and mesothelioma.6