On June 4, 2018 Adaptimmune Therapeutics plc (Nasdaq:ADAP), a leader in T-cell therapy to treat cancer, reported a safety update from its two ongoing pilot studies with SPEAR T-cells targeting MAGE-A10 in non-small cell lung cancer (NSCLC) and the triple tumor study in bladder, melanoma, and head & neck cancers at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) annual meeting (Press release, Adaptimmune, JUN 4, 2018, View Source;p=RssLanding&cat=news&id=2352954 [SID1234527130]).

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!

"Based on these safety data, we are enrolling patients and dosing at the target dose of one billion transduced cells in both MAGE-A10 studies, and we anticipate response data later this year," said Rafael Amado, Adaptimmune’s Chief Medical Officer. "Given our preclinical validation and safety testing data, as well as available clinical results, we anticipate that MAGE-A10 SPEAR T-cells will continue to have an acceptable safety profile as we dose patients in higher cell dose cohorts."

Safety Update
A safety update from the two ongoing MAGE-A10 pilot studies was presented during a poster session (data cut-off 04 May 2018):

Eight patients in the 100 million cell safety cohorts received MAGE-A10 SPEAR T-cells in the two ongoing pilot studies: 3 in Cohort 1 of the triple tumor study, and 5 in Cohort 1a of the NSCLC study
Out of the eight patients treated in the safety cohorts, seven received 100 million transduced SPEAR T-cells, and one patient in the triple tumor study received 90 million cells
There were no deaths attributable to SPEAR T-cell therapy
To date, there has been no evidence of off-target toxicity
There were two events of cytokine release syndrome (CRS), both in the NSCLC study: one Grade 4 and one Grade 1; both events resolved
The Grade 4 event of CRS was considered a dose limiting toxicity (DLT), at the time, and cohort 1a of the NSCLC study was expanded from 3 to 6 patients
Overall, most adverse events were consistent with those typically experienced by cancer patients undergoing cytotoxic chemotherapy or other cancer immunotherapies
While no anti-tumor effects were observed at the 100 million cell dose level, transduced SPEAR T‑cells cells were detectable in peripheral blood
Although cells were readily detectable, observed SPEAR T-cell peak expansion was approximately tenfold lower than what was seen at doses of at least one billion cells in other studies, such as those with NY-ESO SPEAR T-cells
After review of these initial safety data by the safety review committee (SRC), the decision was made to escalate to the next dose of one billion transduced MAGE-A10 SPEAR T-cells in the triple tumor and the NSCLC study. One billion cells was the therapeutic threshold dose observed with SPEAR T‑cells targeting NY-ESO in the synovial sarcoma pilot study.

Response data from these ongoing studies is anticipated throughout the remainder of 2018.

Overview of Study Designs

Open-label studies of MAGE-A10 SPEAR T-cells in patients with NSCLC; bladder, melanoma, or head & neck cancers (known as ‘the triple tumor study)
Patients are screened under a separate protocol (Screening Protocol: NCT02636855) to identify those who have the relevant HLA-A*02 alleles and MAGE-A10 tumor expression
Both trials are first-in-human studies utilizing a modified 3+3 design with escalating doses of 0.1, 1.0 and 1-6 x 109 transduced SPEAR T-cells to evaluate safety, including DLTs
After completing Group 3 (1-6 x 109 transduced cells), doses up to 10 billion (1.0 x 1010) transduced cells will be included
The DLT observation period was the first 30 days following SPEAR T-cell infusion for each patient in the initial safety cohorts (100 million cells) and is 7 days in subsequent (≥1 billion cells) cohorts
NSCLC Study:
Patients must be at least 18 years of age and have Stage IIIb or IV NSCLC, have failed at least one platinum‑containing regimen (may have received CPIs), have measurable disease, ECOG 0-1, adequate organ function, and be without brain metastases, history of severe autoimmune disease or current uncontrolled illness
The lymphodepletion regimen for patients receiving:
100 million transduced cells was cyclophosphamide alone (1800 mg/m2/day) for 2 days
One billion (1.0 x 109) transduced cells is cyclophosphamide 600mg/m2/day and fludarabine 30 mg/m2/day on Days -7, -6 and -5
One to six billion (1-6 x 109) or up to ten billion (1.0 x 1010) transduced cells is cyclophosphamide 600mg/m2/day on Days -7, -6, -5 and fludarabine 30 mg/m2/day on Days -7, -6, -5, and -4
Efficacy is assessed by response rate, duration of response, progression-free survival, and overall survival at weeks 4, 8, and 12, month 6, and then every 3 months (for 2 years) and then every 6 months until confirmation of disease progression
Triple Tumor Study:
Patients must be at least 18 years of age and have inoperable or metastatic (advanced) urothelial "bladder" cancer, melanoma, or squamous cell head and neck tumors; and, have received standard of care therapies and have progressive disease
The lymphodepletion regimen for patients receiving:
100 million transduced cells was cyclophosphamide 600mg/m2/day and fludarabine 30 mg/m2/day on Days -7, -6 and -5
One billion (1.0 x 109) transduced cells is cyclophosphamide 600mg/m2/day and fludarabine 30 mg/m2/day on Days -7, -6 and -5
One to six billion (1-6 x 109) or up to ten billion (1.0 x 1010) transduced cells is cyclophosphamide 600mg/m2/day on Days -7, -6, -5 and fludarabine 30 mg/m2/day on Days -7, -6, -5, and -4
Efficacy is assessed by overall response rate, best overall response, time to response, duration of response, duration of stable disease, progression-free survival, and overall survival at weeks 6, 12, 18, and 24 weeks, and then every 3 months until confirmation of disease progression
Conference Call Information
The Company will host a live teleconference to answer questions about the updated safety data today, June 4, 2018, at 8:00 a.m. EDT (1:00 p.m. BST). The live webcast of the conference call will be available via the events page of Adaptimmune’s corporate website at https://bit.ly/2shwniM. An archive will be available after the call at the same address. To participate in the live conference call, if preferred, please dial please dial +1-(833) 652-5917 (U.S.) or +1-(430) 775-1624 (International). After placing the call, please ask to be joined into the Adaptimmune conference call and provide the confirmation code (9199456).

On June 4, 2018 MEI Pharma, Inc. (Nasdaq: MEIP), a pharmaceutical company focused on leveraging its extensive development and oncology expertise to identify and advance new therapies for cancer, reported that data presented at ASCO (Free ASCO Whitepaper) 2018 from an investigator-initiated study of ME-344 in patients with HER2 negative breast cancer demonstrate evidence of inhibition of tumor proliferation as measured by Ki-67 reductions (Press release, MEI Pharma, JUN 4, 2018, View Source [SID1234527129]). These interim data are consistent with preclinical results indicating ME-344’s potential to reverse resistance to anti-angiogenic therapy, thereby warranting the continuation of the ongoing study.

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!

"The goal of this study is to gain a better understanding of the escape pathways that may be utilized by tumors against antiangiogenic therapeutics. The interim results from this study suggest that there may be an important therapeutic role for mitochondrial inhibitors like ME-344, providing a potential novel mechanism to improve patient outcomes in combination with antiangiogenic therapeutics," stated the study principal investigator, Miguel Quintela-Fandino, M.D., Ph.D., Director of the Clinical Research Program, Centro Nacional De Investigaciones Oncologicas, Madrid, Spain.

"We are looking forward to continuing our work with Dr. Quintela-Fandino as we further elucidate the opportunity to advance ME-344 as part of a novel approach for the treatment of cancer," said Daniel P. Gold, Ph.D., president and chief executive officer of MEI Pharma.

The ME-401 ASCO (Free ASCO Whitepaper) 2018 poster can be accessed on the MEI Pharma website.

ME-344 Clinical Data
The ongoing study is a multicenter, investigator-initiated, randomized, open-label, clinical trial evaluating ME-344 in a total of up to 40 patients with HER2-negative breast cancer in combination with the vascular endothelial growth factor inhibitor bevacizumab (marketed as Avastin). Patients are randomized one-to-one to either ME-344 plus Avastin or saline plus Avastin. The interim data review was predefined to take place after 20 patients were randomized.

The primary efficacy endpoint is inhibition of cell proliferation as measured by Ki-67 reductions. Mean absolute (relative) Ki67 decreases were 5.13 (29%) and 1.2 (9%) in the active versus control arms (P=0.06). Patients with standardized uptake values via PET scan ≥ 10% experienced an absolute average Ki67 decrease of 16.6 vs. 2.3 in the active versus control arms (P=0.19). Treatment was generally well tolerated; two Grade 3 adverse events (high blood pressure) were reported, 1 in each arm, and deemed related to bevacizumab.

About ME-344
ME-344 is a novel, tumor selective, isoflavone-derived mitochondrial inhibitor drug candidate. It directly targets the OXPHOS complex 1, a pathway involved in the production of adenosine triphosphate, or ATP, in the mitochondria. Treatment of tumor cells with ME-344 results in a rapid loss of ATP and cancer cell death. ME-344 demonstrated evidence of single-agent activity against refractory solid tumors in a Phase I study, and in preclinical studies, tumor cells treated with ME-344 resulted in a rapid loss of ATP and cancer cell death.

In addition to single-agent activity, ME-344 may also have potential in combination with antiangiogenic therapeutics. While antiangiogenics reduce the rate of glycolysis in tumors as a mechanism to block growth, tumor metabolism often shifts to mitochondrial metabolism to continue energy production to support continued tumor proliferation. In such cases of tumor plasticity in the presence of treatment with antiangiogenics, targeting the alternative metabolic source with ME-344 may open an important therapeutic opportunity.

On June 4, 2018 MEI Pharma, Inc. (NASDAQ: MEIP) a pharmaceutical company focused on leveraging its extensive development and oncology expertise to identify and advance new therapies for cancer, reported that data presented at ASCO (Free ASCO Whitepaper) 2018 from a Phase 1b study of ME-401 demonstrate a 90% objective response rate in patients with relapsed or refractory follicular lymphoma (FL), chronic lymphocytic lymphoma (CLL) and small lymphocytic lymphoma (SLL) (Press release, MEI Pharma, JUN 4, 2018, View Source [SID1234527128]). Based on the data in this program, MEI anticipates progressing into a single-agent registration study later in 2018 for the treatment of adults with relapsed or refractory follicular lymphoma. ME-401 is a next-generation selective oral inhibitor of PI3K delta.

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!

"The clinical evidence we are accumulating from the Phase 1b study of ME-401 is very promising; the data demonstrate a 90% response rate across all patients with relapsed or refractory FL, CLL and SL, and an 86% rate in patients with relapsed or refractory follicular lymphoma," said Daniel P. Gold, Ph.D., president and chief executive officer of MEI Pharma. "There continues to be a need for effective treatment options among patients with relapsed or refractory follicular lymphoma. We therefore anticipate moving into a single-agent registration study by the end of the year"

The ME-401 ASCO (Free ASCO Whitepaper) 2018 poster can be accessed on the MEI Pharma website.

ME-401 Phase 1b Data
ME-401 is being evaluated in a Phase 1b dose escalation study in patients with relapsed or refractory FL, CLL and SLL. As of May 14, 2018, 46 patients were enrolled: 31 patients received monotherapy and 30 were evaluable for efficacy (12 patients at 60 mg, 12 patients at 120 mg and six patients at 180 mg). Based on the data, the Company determined that no further dose escalation was required. An expansion cohort of up to 30 patients with FL, CLL and SLL was added to further evaluate the safety and efficacy of ME-401 as a single agent at the 60 mg dose. An additional 15 patients are enrolled in the study arm evaluating ME-401 (60 mg) in combination with rituximab (marketed as Rituxan) in patients with various B cell malignancies.

ME-401 administered as a single-agent achieved a high response rate of 90% in all evaluable patients as well as a high rate of 86% in the group of patients with FL:

On June 4, 2018 Idera Pharmaceuticals, Inc. (NASDAQ:IDRA), a clinical-stage biopharmaceutical company developing toll-like receptor and RNA therapeutics for patients with rare cancers and rare diseases, reported results from the ongoing ILLUMINATE-204 trial investigating tilsotolimod, Idera’s intratumorally-delivered Toll-like Receptor (TLR) 9 agonist, in combination with ipilimumab (Yervoy*) (Press release, Idera Pharmaceuticals, JUN 4, 2018, View Source [SID1234527126]). Current data show an overall response rate (ORR) of 38 percent following treatment with the combination of tilsotolimod and ipilimumab. This includes 2 complete responses (1 ongoing for 23 months) and an ongoing PR for 12 months. These results will be presented at the 2018 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in Chicago, IL during the poster display session from 1:15-4:45 PM CT and as the subject of a poster discussion session from 4:45-6:00 PM CT.

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 have clinical evidence that tilsotolimod activates both the innate and adaptive immune responses, and when used in combination with a checkpoint inhibitor like ipilimumab, triggers immune responses in previously resistant tumors," stated Adi Diab, M.D., Lead Trial Investigator, Assistant Professor, Department of Melanoma Medical Oncology, Division of Cancer Medicine, University of Texas, MD Anderson Cancer Center. "In patients with metastatic melanoma receiving pembrolizumab who switched to single agent ipilimumab at the time of disease progression the reported ORR was 13%. The ORR of 38% observed in the ILLUMINATE-204 study and the duration of response, which is ongoing in most of the responders, is particularly encouraging and suggests that the combination of tilsotolimod and ipilimumab is a very promising strategy for treating patients with metastatic melanoma whose cancer does not respond to PD-1 therapy alone."

The data available for presentation includes 26 patients whose disease had progressed on anti PD-1 therapy. 21 were evaluable for efficacy [reached first disease assessment as of 09 May 2018], all of whom received tilsotolimod in combination with ipilimumab. The median age of patients at this time is 68.5; 23 of the 26 patients (~88%) had Stage IV melanoma and 11 (42.3%) M1c. 11 of the 26 patients presented with BRAF mutations. The ILLUMINATE-204 trial is planned to enroll up to 60 patients at the 8 mg dose of tilsotolimod, with enrollment completion expected by the end of 2018. Additionally, Idera initiated a global Phase 3 trial of tilsotolimod in combination with ipilimumab (ILLUMINATE-301) compared with ipilimumab alone in anti-PD-1 refractory melanoma in the first quarter of 2018.

ILLUMINATE-204 Key Findings:

21 patients treated with the 8 mg dose of tilsotolimod in combination with ipilimumab have had disease evaluations;
Confirmed RECIST v1.1 responses (including 2 Complete Response [CR]) were observed in 8 of these 21 subjects (38.1%);
Six of 8 responses are ongoing (1 CR ongoing for nearly 2 years); median duration of response for these 8 has not yet been reached;
Overall 15 patients out of 21 evaluable for efficacy (71.4%) experienced disease control (CR, PR, or SD);
The combination regimen is generally well tolerated. 6/26 subjects (23%) had immune-related toxicities indicating that IMO-2125 + ipilimumab does not appear to add toxicity versus ipilimumab alone.
Injection-related toxicities were grade 1-2 transient fever and flu-like symptoms lasting <48 hours; and,
15/26 patients (57.7%) with lesions accessible only by image-guided injection (5 deep visceral lesions and 10 lymph nodes) were included.
Additionally:

A RECIST v1.1 PR of > 2 year duration is ongoing in a patient treated with tilsotolimod 4 mg in combination with ipilimumab; and
A RECIST v1.1 CR is ongoing in a patient treated with tilsotolimod 16 mg in combination with pembrolizumab.
"Patients with melanoma and metastatic disease progressing on anti-PD-1 therapy have limited treatment options and need rapid intervention," stated Joanna Horobin, M.B., Ch.B., Idera’s Chief Medical Officer. "We have previously reported that tilsotolimod produces maturation of pDCs to activate the immune system within 24 hours of dosing to provide a synergistic anti-tumor effect when combined with ipilimumab. The combination is generally well tolerated; specifically less than a quarter of patients experienced immune-related toxicities. Moreover, the ability to safely deliver tilsotolimod into deep visceral lesions and lymph nodes significantly broadens the opportunity to provide this new therapeutic approach to patients. This becomes particularly important as we expand the clinical program of tilsotolimod beyond melanoma to other metastatic tumor types which rarely have superficial lesions available for injection."

A copy of the poster presentation is currently available on Idera’s corporate website at View Source

Two additional abstracts were accepted for publication by the review committee:

Title: Preliminary safety of deep/visceral (D/V) image guided (IG) intratumoral
injection (ITI) of IMO-2125.
Abstract Number
For Publication: e15150
Author: Hani Babiker, MD, University of Arizona Cancer Center

Title: Right tumor, right time: Systematic methodology for fiducial marker
placement to achieve reliable and reproducible image guided (IG)
delivery of intratumoral immunotherapy into deep/visceral (D/V) lesions
and target-lesion imaging follow-up
Abstract Number
For Publication: e24137
Author: Gregory John Woodhead, MD, PhD, University of Arizona Cancer Center
Investor Event and Webcast
The company plans to hold an investor/analyst event at the ASCO (Free ASCO Whitepaper) Annual Meeting on Monday, June 4, 2018, beginning at 6:30 PM CT, which will feature a presentation by ILLUMINATE-204 lead investigator Adi Diab, MD as well as Q&A with attendees and Idera management. As a convenience to those unable to attend in person, the event will be webcast.

The webcast can be accessed live or in archived form in the "Investors" section of the company’s website at www.iderapharma.com. The company plans to post a slide presentation on Monday, June 4, 2018 to the Idera corporate website in the "Investors" section which will be referenced during the conference call.

About Tilsotolimod (IMO-2125)
Tilsotolimod is a TLR 9 agonist that received Fast Track Designation from the US Food and Drug Administration (FDA) in 2017 for the treatment of anti-PD-1 refractory melanoma, in combination with ipilimumab as well as orphan drug designation from the FDA for the treatment of melanoma Stages IIb to IV. It signals the immune system to create and activate cancer-fighting cells (T-cells) to target solid tumors. Currently approved immuno-oncology treatments, specifically check-point inhibitors, work for some but not all, as many patients’ immune response is missing or weak and thus they do not benefit from the checkpoint therapy. Intratumoral injections with tilsotolimod are designed to selectively enable the T-cells to recognize and attack cancers that remained elusive and unrecognized by the immune system exposed to checkpoint inhibitors alone, while limiting toxicity or impact on healthy cells in the body.

About ILLUMINATE-204
The ILLUMINATE-204 study (2125-204) is for patients who have metastatic melanoma for whom treatment with an anti-PD-1 drug like Keytruda** (pembrolizumab) or Opdivo* (nivolumab) has failed. Melanoma is the most dangerous type of skin cancer. When it is metastatic, it means that the melanoma has spread to different parts of the body. ILLUMINATE-204 is a multi-center, two-arm Phase 1/2 study that tests the safety and effectiveness of tilsotolimod in combination with either ipilimumab (Yervoy) or pembrolizumab (Keytruda) for the treatment of patients with anti-PD-1 refractory metastatic melanoma.

For additional details about ILLUMINATE-204, please go to clinicaltrials.gov and search for study identifier NCT02644967.

About ILLUMINATE-301
The ILLUMINATE-301 study (2125-MEL-301) is for patients who have metastatic melanoma for whom treatment with an anti-PD-1 drug like Keytruda (pembrolizumab) or Opdivo (nivolumab) has failed. ILLUMINATE-301 is a global, multi-center, randomized Phase 3 study that compares the effectiveness and safety between two treatment groups: IMO-2125 combined with ipilimumab (Yervoy) versus ipilimumab given alone.

For additional details about ILLUMINATE-301, please go to clinicaltrials.gov and search for study identifier NCT03445533.

About Metastatic Melanoma
Melanoma is a type of skin cancer that begins in a type of skin cell called melanocytes. As is the case in many forms of cancer, melanoma becomes more difficult to treat once the disease has spread beyond the skin to other parts of the body such as the lymphatic system, liver or other visceral organs (metastatic disease). Because melanoma occurs in younger individuals, the years of life lost to melanoma are also disproportionately high when compared with other cancers. Although melanoma is a rare form of skin cancer, it comprises over 75% of skin cancer deaths. The American Cancer Society estimates that there were approximately 76,000 new invasive melanoma cases and 10,000 deaths from the disease in the USA in 2016. Additionally, according to the World Health Organization, about 132,000 new cases of melanoma are diagnosed around the world every year.

On June 4, 2018 Hutchison China MediTech Limited ("Chi-Med") (AIM/Nasdaq: HCM) reported that further data from the FRESCO Phase III study in 416 patients with locally advanced or metastatic colorectal cancer ("CRC") were presented at the 2018 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) ("ASCO") Annual Meeting, held in Chicago, Illinois from June 1 to 5, 2018 (Press release, Hutchison China MediTech, JUN 4, 2018, https://www.chi-med.com/fresco-data-at-asco-2018/ [SID1234527125]).

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!

Fruquintinib is a highly selective and potent oral inhibitor of vascular endothelial growth factor ("VEGF") receptors 1, 2 and 3. The FRESCO dataset is a part of the New Drug Application ("NDA") filed and accepted by the China National Drug Administration (the "CNDA"). Additional clinical trials are ongoing in China for lung cancer (the third-line FALUCA Phase III study and the first-line Iressa combination Phase II study) and gastric cancer (the second-line FRUTIGA Phase III study), as well as in the United States (Phase I bridging study).

The two presentations were as follows:

Subgroup analysis by prior anti-VEGF or anti-EGFR target therapy in FRESCO, a randomized, double-blind, Phase III trial comparing fruquintinib versus placebo plus best supportive care in Chinese patients with metastatic colorectal cancer

Presenter: Ruihua Xu
Other Authors: Jin Li, Yu-Xian Bai, Yanhong Deng, Lei Yang, Haijun Zhong, Zhendong Chen, Hongming Pan, Weijian Guo, Yongqian Shu, Ying Yuan, Jianming Xu, Lin Shen, Ning Wang, Xin Wang, Haidong Chi, Jack Peng, Ye Hua, Weiguo Su, Shukui Qin
Time & Location: Sunday, June 3, 08:00 – 11:30 CDT; Hall A, Poster Board: #30
Session: Gastrointestinal (Colorectal) Cancer
Abstract No. & Link: #3537; abstracts.asco.org/214/AbstView_214_215579.html
Poster Link:[ ]: 16ealJfSDOCUUwuY6Icm22

In FRESCO, fruquintinib demonstrated a statistically significant and clinically meaningful benefit in third-line metastatic CRC patients in China. This analysis explored possible effects of prior target therapy on the efficacy and safety of fruquintinib by analyzing the subgroups of patients with prior target therapy ("PTT") and those without prior target therapy ("non-PTT"). The results of this analysis showed that fruquintinib had clinically meaningful benefits in third-line metastatic CRC patients regardless of PTT without observed accumulative toxicity.

Results previously presented at the 20th Annual Meeting of the Chinese Society of Clinical Oncology showed that the benefits of fruquintinib were generally consistent across all subgroups. Among a total of 278 fruquintinib-treated patients, 111 received PTT. In the PTT subgroup, fruquintinib significantly prolonged overall survival ("OS") (Median OS: 7.69 months vs 5.98 months; HR = 0.63; p = 0.023) and progression-free survival ("PFS") (Median PFS: 3.65 months vs 1.84 months; HR = 0.24; p < 0.001) compared to placebo. Patients who received prior anti-VEGF treatment (N = 84) also benefited from fruquintinib in OS (Median 7.20 months vs 5.91 months; HR = 0.68; p=0.066) and PFS (Median 3.48 months vs 1.84 months; HR = 0.24; p < 0.001). In the non-PTT subgroup, the median OS was 10.35 months for fruquintinib vs 6.93 months for placebo (HR = 0.63; p = 0.01), and the median PFS for fruquintinib was 3.81 months vs 1.84 months for placebo (HR = 0.28; p < 0.001).

Additional data presented at this year’s ASCO (Free ASCO Whitepaper) showed that there were no observed accumulative Grade ≥3 treatment-emergent adverse events in the PTT subgroup. The Grade ≥3 treatment-emergent adverse events rates of fruquintinib were similar in PTT and non-PTT subgroup (61.3% and 61.1%). This subgroup analysis result is consistent with the previously reported FRESCO intent-to-treatment population result.

Quality-adjusted time without symptoms or toxicity (Q-TWiST) of patients with metastatic colorectal cancer treated with fruquintinib in the randomized Phase III FRESCO trial

Presenter: Yu-Xian Bai
Other Authors: Hongyan Li, Ning Wang, Xiaojun Guo, Wei Wang, Songhua Fan, Jian-Ming Xu, Lin Shen
Time & Location: Sunday, June 3, 08:00 – 11:30 CDT; Hall A, Poster Board: #37
Session: Gastrointestinal (Colorectal) Cancer
Abstract No. & Link: #3544; abstracts.asco.org/214/AbstView_214_224293.html
Poster Link[ ]: 4l9OppVsv6UKE20CM4uQYy

This ad-hoc analysis aimed to compare the quality-adjusted survival between the two arms of the FRESCO study using quality-adjusted time without symptoms or toxicity ("Q-TWiST") methodology and to investigate the Q-TWiST benefit of fruquintinib treatment among subgroups. Q-TWiST is a tool to evaluate relative clinical benefit-risk from patient’s perspective and has been widely used in oncology treatment assessment. The survival time for each patient was divided into 3 portions: TOX (time with ≥ Grade 3 toxicity before progression), TWiST (time without symptoms or ≥ Grade 3 toxicity), and REL (time from progression or relapse until death or end of follow-up).

Patients treated with fruquintinib had longer Q-TWiST periods compared to patients treated with placebo. Q-TWiST benefits were observed regardless of prior lines of chemotherapy and target treatment with anti-VEGF or anti-EGFR. The relative improvement of Q-TWiST with fruquintinib represents a clinically important quality-of-life benefit for metastatic CRC patients.

Further information about the ASCO (Free ASCO Whitepaper) annual meeting is available at am.asco.org.

About Fruquintinib
Fruquintinib (HMPL-013) is a highly selective small molecule drug candidate that has been shown to inhibit VEGF receptors 24 hours a day via an oral dose, with lower off-target toxicities compared to other targeted therapies. Its tolerability, along with its clean drug-drug interaction profile demonstrated to date, may enable rational combination with other cancer therapies such as in our ongoing clinical trials of fruquintinib in combination with chemotherapy and targeted therapy. VEGF receptors play a pivotal role in tumor-related angiogenesis, and inhibition of VEGFR represents an important therapeutic strategy in blocking the development of new blood vessels essential for tumors to grow and invade.

About Fruquintinib in CRC in China
The CNDA, formerly the China Food and Drug Administration, acknowledged acceptance of the NDA for fruquintinib for the treatment of patients with advanced CRC in June 2017. Fruquintinib was subsequently awarded priority review status in view of its significant clinical value, according to a CNDA announcement in September 2017. The NDA is supported by data from the successful FRESCO study, which was highlighted in an oral presentation at the ASCO (Free ASCO Whitepaper) Annual Meeting held on June 5, 2017. Additional details about this study can be found at clinicaltrials.gov, using identifier NCT02314819. The FRESCO study followed an initial Phase I trial in 40 solid tumor patients, a Phase Ib study in 62 CRC patients, and a Phase II clinical trial in 71 CRC patients.

Other Fruquintinib Development Programs
Lung cancer in China: Fruquintinib is being studied in China in a Phase III registration study, known as FALUCA, in non-small cell lung cancer ("NSCLC") patients. FALUCA is a randomized, double-blind, placebo-controlled, multi-center study of fruquintinib targeted at treating patients with advanced non-squamous NSCLC who have failed two lines of systemic chemotherapy. The trial completed enrollment of 527 patients in February 2018 (clinicaltrials.gov identifier NCT02691299). It was initiated following a similar Phase II clinical trial in 91 third-line NSCLC patients. Results of the Phase II study were highlighted in an oral presentation at the 17th World Conference on Lung Cancer on December 6, 2016 (clinicaltrials.gov identifier NCT02590965).

Along with FALUCA, fruquintinib is concurrently being studied in a Phase II study in combination with Iressa (gefitinib) in the first-line setting for patients with advanced or metastatic NSCLC (clinicaltrials.gov identifier NCT02976116). Preliminary results were highlighted in an oral presentation at the 18th World Conference on Lung Cancer on October 16, 2017.

Gastric cancer in China: In October 2017, Chi-Med initiated a pivotal Phase III clinical trial of fruquintinib in combination with Taxol (paclitaxel), known as the FRUTIGA study, for the treatment of patients with advanced gastric or gastroesophageal junction ("GEJ") adenocarcinoma. The FRUTIGA study is a randomized, double-blind, placebo-controlled, multi-center trial expected to enroll over 500 gastric or GEJ adenocarcinoma patients who have progressed after first-line standard chemotherapy (clinicaltrials.gov identifier NCT03223376). The FRUTIGA study follows a Phase Ib/II clinical trial that demonstrated that combination therapy of fruquintinib and Taxol in such patients was generally well-tolerated with promising tumor response (clinicaltrials.gov identifier NCT02415023).

In China, fruquintinib is jointly developed with Eli Lilly and Company.

United States bridging trial: In December 2017, Chi-Med initiated a multi-center, open-label, Phase I clinical study to evaluate the safety, tolerability and pharmacokinetics of fruquintinib in U.S. patients with advanced solid tumors (clinicaltrials.gov identifier NCT03251378).
About Chi-Med
Chi-Med is an innovative biopharmaceutical company which researches, develops, manufactures and sells pharmaceuticals and healthcare products. Its Innovation Platform, Hutchison MediPharma Limited, focuses on discovering and developing innovative therapeutics in oncology and autoimmune diseases for the global market. Its Commercial Platform manufactures, markets, and distributes prescription drugs and consumer health products in China.

Chi-Med is majority owned by the multinational conglomerate CK Hutchison Holdings Limited (SEHK: 1). For more information, please visit: www.chi-med.com.

Iressa is a trademark of the AstraZeneca PLC group of companies. Taxol is a trademark of The Bristol-Myers Squibb Company group of companies.