On June 5, 2017 MorphoSys AG (FSE: MOR; Prime Standard Segment, TecDAX; OTC: MPSYY) reported safety and efficacy data from an ongoing phase 2 clinical trial ("L-MIND" study) evaluating MOR208 in combination with lenalidomide in patients with relapsed or refractory (R/R) diffuse large B cell lymphoma (DLBCL) (Press release, MorphoSys, JUN 5, 2017, View Source [SID1234519402]). DLBCL is the most common form of non-Hodgkin’s lymphoma. Data were reported during a poster presentation at the 2017 Annual Meeting of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) in Chicago/USA. MOR208 is an Fc-enhanced investigational antibody directed against CD19.

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"We are very excited having seen the preliminary data from the first 44 patients of our ongoing phase 2 L-MIND trial. We are particularly optimistic about the level of response rates that we have seen so far, especially complete responses. For DLBCL patients who relapse after their first-line treatment, current treatment options are very limited. We are therefore exploring potential new treatment regimens with MOR208 for this difficult-to-treat patient group", commented Dr. Malte Peters, Chief Development Officer of MorphoSys AG.

44 patients were enrolled in the study at data cut-off, 34 of whom were evaluable for efficacy assessment. Preliminary data show an objective response in 19 out of 34 patients (ORR: 56%). Complete remission was seen in 11 out of 34 patients (CR: 32%). 16 out of 19 patients in whom responses were recorded, were still on study at time of data-cut off.

No infusion-related reactions were reported for MOR208. The most frequent adverse events observed of grade 3 or higher were hematological, comprising neutropenia, thrombocytopenia, and leukopenia, seen in 32%, 9%, and 9% of patients, respectively. To date, 27% of patients required a reduction of the lenalidomide dose due to side effects. No unexpected safety-related effects were observed.

The L-MIND trial (Lenalidomide plus MOR208 in DLBCL) is a single-arm, open-label, multicenter study of MOR208 in combination with lenalidomide. The trial will enroll approximately 80 patients with relapsed or refractory DLBCL after up to three prior lines of therapy, with at least one prior therapy including an anti-CD20 targeting therapy (e.g. rituximab). Patients in the trial could not be candidates for high-dose chemotherapy or autologous stem cell transplantation. Patients enrolled in the trial had a median age of 73 years.

In addition to the preliminary data from the phase 2 L-MIND study with MOR208 and lenalidomide in R/R DLBCL, two "trial-in-progress" posters about MOR208 were presented at ASCO (Free ASCO Whitepaper) 2017 illustrating the study designs of two other ongoing clinical combination trials of MOR208: the phase 2/3 randomized, "B-MIND" study comparing MOR208 plus bendamustine vs. rituximab plus bendamustine in patients with R/R DLBCL; and the phase 2 "COSMOS" study in R/R chronic lymphocytic leukemia (CLL) patients, who had previously discontinued treatment with a Bruton tyrosine kinase (BTK) inhibitor. The COSMOS trial is currently investigating MOR208 in combination with idelalisib.

Details of the MOR208 presentations at ASCO (Free ASCO Whitepaper) 2017

Abstract #7514, poster board #276

L-MIND: MOR208 combined with lenalidomide (LEN) in patients with relapsed or refractory diffuse large B-cell lymphoma (R-R DLBCL) – A single-arm phase 2 study

The poster will be presented during the session, "Hematologic Malignancies – Lymphoma and Chronic Lymphocytic Leukemia," held on June 5, 2017 (8:00 AM-11:30 AM CDT, poster hall). The results will also be highlighted during a poster discussion session about CD19 targeting therapies on June 5, 2017 (1:15 PM-2:30 PM CDT, room E354b).

Abstract #TPS7571, poster board #330b

B-MIND: MOR208 plus bendamustine (BEN) versus rituximab (RTX) plus BEN in patients with relapsed or refractory (R-R) diffuse large B-cell lymphoma (DLBCL): An open-label, randomized phase 2/3 trial

The poster will be presented in the "Hematologic Malignancies – Lymphoma and Chronic Lymphocytic Leukemia" session on June 5, 2017 (8:00 AM-11:30 AM CDT, poster hall).

Abstract #TPS7567, poster board#328b

COSMOS: MOR208 plus idelalisib or venetoclax in patients with relapsed or refractory (R/R) chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) previously treated with a Bruton’s tyrosine kinase inhibitor (BTKi) – A two-cohort phase 2 study

The poster will be presented in the "Hematologic Malignancies – Lymphoma and Chronic Lymphocytic Leukemia" session on June 5, 2017 (8:00 AM-11:30 AM CDT, poster hall).

MorphoSys will hold an Investor & Analyst Event at the 2017 ASCO (Free ASCO Whitepaper) Annual Meeting on June 5, 2017, at 6:30pm CDT (June 6, 2017: 1:30am CEST). Clinical data for MorphoSys’s investigational agents MOR208 and MOR202 will be presented by clinical investigators and company representatives.

A replay and the presentation will be made available at View Source

About CD19 and MOR208
CD19 is broadly and homogeneously expressed across different B cell malignancies including DLBCL and CLL. CD19 has been reported to enhance B cell receptor (BCR) signaling, which is assumed important for B cell survival, making CD19 a potential target in B cell malignancies.
MOR208 (previously Xmab(R)5574) is an Fc-enhanced monoclonal antibody directed against CD19. Fc-modification of MOR208 is intended to lead to a significant potentiation of antibody-dependent cell-mediated cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP), thus aiming to improve a key mechanism of tumor cell killing. Furthermore, MOR208 has been observed in preclinical models to induce direct apoptosis by binding to CD19, which is assumed to be a crucial component for B cell receptor (BCR) signaling.
MorphoSys AG is clinically investigating MOR208 as a therapeutic option in B cell malignancies in a number of ongoing combination trials. A phase 2 combination trial (L-MIND study) was started in March 2016 and is designed to investigate the safety and efficacy of MOR208 in combination with lenalidomide in approximately 80 patients with relapsed/refractory DLBCL. The phase 2/3 B-MIND study was started in August 2016 and transitioned into its phase 3 pivotal part in June 2017 following a recommendation of the IDMC based on the available data from the phase 2 initial safety evaluation. The B-MIND study is designed to investigate MOR208 in combination with the chemotherapeutic agent bendamustine in relapsed/refractory DLBCL patients who are not eligible for high-dose chemotherapy (HDC) and autologous stem cell transplantation (ASCT) in comparison to the combination of the anti-CD20 antibody rituximab plus bendamustine. Furthermore, in December 2016, a third phase 2 combination trial was started with MOR208 evaluating the antibody in patients with relapsed/refractory CLL after discontinuation of a prior Bruton tyrosine kinase (BTK) inhibitor therapy (e.g. ibrutinib). Currently MOR208 is being studied in combination with idelalisib; a second study arm of MOR208 plus venetoclax is currently in preparation.

On June 5, 2017 Helsinn, a Swiss pharmaceutical group focused on building quality cancer care products, and MEI Pharma, Inc. (Nasdaq: MEIP), an oncology company focused on the clinical development of novel therapies for cancer, reported findings from a genetic mutation analysis of patients in a Phase II clinical study of the investigational drug pracinostat and azacitidine in acute myeloid leukemia (AML), including a significant correlation between genetic mutations in the DNA methylation pathway and clinical response (Press release, MEI Pharma, JUN 5, 2017, View Source [SID1234519401]). These data are being presented today at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in Chicago.

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Available samples from 41 of the 50 patients enrolled in the Phase II study were sequenced to characterize the genetic mutation profile of these patients. The overall mutation profile of the patients in this study appear to be generally typical of an older population with AML1 and are also common in myelodysplastic syndrome (MDS)2. The most frequent mutations, occurring in 37% of samples studied (15 41), were found in the DNA methylation pathway, including DNMT3A, IDH1, IDH2 and TET2. Patients with these mutations had a complete response (CR) rate of 60%, a significant improvement (p=0.027) over patients with the wild-type genes (22%).

Notably, the phase II analysis also showed that median overall survival was roughly equivalent in patients with mutations typically associated with de novo AML (18.1 months) and secondary AML (17.7 months). In a recent study, the standard-of-care regimen of cytarabine and daunorubicin (7+3) in patients with secondary AML showed a median overall survival of 5.95 months3.

"This mutational analysis enabled us to identify frequently occurring genetic abnormalities that may predict outcomes in older AML patients treated with the combination of pracinostat and azacitidine," said Dr. Guillermo Garcia-Manero, MD Anderson Cancer Center, principal investigator of the study. "In addition, we confirmed that the mutation profile in the Phase II AML study was representative not only of the larger population of older AML patients, but common in MDS patients as well. Finally, longitudinal sequencing analyses showed that continued treatment with pracinostat and azacitidine increases the rate of minimal residual disease clearance. These findings combine to support the upcoming Phase III study of pracinostat plus azacitidine in AML as well as the Phase II dose-optimization study of pracinostat and azacitidine in high and very high MDS."

A copy of the poster, entitled "Correlation Between Mutation Clearance and Clinical Response in Elderly Patients with Acute Myeloid Leukemia (AML) Treated with Azacitidine and Pracinostat," is now available at www.meipharma.com. These data will also be presented at the European Hematology Association (EHA) (Free EHA Whitepaper) Annual Congress in Madrid on Friday, June 23, 2017.

Results from the Phase II study of pracinostat and azacitidine in elderly patients with AML showed a median overall survival of 19.1 (95%CI: 10.0-26.5) months, one-year survival of 62% and a CR rate of 42%. CR rate and overall survival were consistent across patient subsets. Responses were durable (median CR+CRi 17.2 months), blast clearance was rapid (median 8 weeks) and maximum clinical benefit required prolonged therapy (> 6 months) in some patients. The combination of pracinostat and azacitidine had no unexpected toxicities. The most common grade 3 4 treatment-emergent adverse events reported in >10% of all patients included thrombocytopenia, febrile neutropenia, neutropenia, fatigue and anemia. These results were presented at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in December 2016.

About Pracinostat
Pracinostat is an oral histone deacetylase (HDAC) inhibitor that is in late stage clinical development. The U.S. Food and Drug Administration has granted Breakthrough Therapy Designation for pracinostat in combination with azacitidine for the treatment of patients with newly diagnosed AML who are ≥75 years of age or unfit for intensive chemotherapy. In August 2016, Helsinn and MEI Pharma entered into an exclusive license, development and commercialization agreement for pracinostat in AML and other potential indications. Site recruitment is ongoing for a global Phase III study of pracinostat and azacitidine in newly diagnosed AML patients who are ≥75 years of age or unfit for intensive induction chemotherapy. A Phase II dose-optimization study of pracinostat and azacitidine in patients with high and very high risk MDS is expected to initiate this month. Pracinostat is an investigational agent and is not approved for commercial use in the U.S.

On June 5, 2017 Juno Therapeutics, Inc. (NASDAQ: JUNO), a biopharmaceutical company developing innovative cellular immunotherapies for the treatment of cancer, reported updated data from the TRANSCEND trial of JCAR017 in relapsed and refractory (r/r) aggressive B cell non-Hodgkin lymphoma (NHL) in a presentation at the 2017 Annual Meeting of the American Society for Clinical Oncology (ASCO) (Free ASCO Whitepaper) (Press release, Juno, JUN 5, 2017, View Source [SID1234519400]).

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JCAR017 is Juno’s investigative chimeric antigen receptor (CAR) T cell product candidate that targets CD19, a protein expressed on the surface of almost all B cell malignancies, and uses a defined composition of CD4 to CD8 T cells and a 4-1BB costimulatory domain, which differentiates it from other current CD19-directed CAR T product candidates.
"Today’s update of data from the TRANSCEND trial shows continued compelling results in patients with a wide range of aggressive NHL," said Sunil Agarwal, M.D., Juno’s President of Research and Development. "We are encouraged by the high rates of durable responses and the early survival data in these patients. We are also encouraged by the early safety data—a majority of patients treated experienced no cytokine release syndrome or neurotoxicity of any grade, which suggests the potential for outpatient administration."

The data presented today by principal investigator Jeremy Abramson, M.D., of Massachusetts General Hospital Cancer Center, were from the multicenter TRANSCEND trial (ASCO Abstract #7513), a Phase 1 study that has treated 71 patients with r/r aggressive B cell NHL, including those with diffuse large B cell lymphoma (DLBCL), follicular lymphoma grade 3B, or mantle cell lymphoma (MCL). This was a dose-finding study of JCAR017, following fludarabine/cyclophosphamide lymphodepletion. Patients were evaluated for pharmacokinetics, disease response, and safety outcomes, including those commonly associated with CAR T cell therapy, such as cytokine release syndrome (CRS) and neurotoxicity (NT). Patients in this study included those excluded from other trials, including those with ECOG 2 performance status, central nervous system (CNS) involvement of their lymphoma, and those relapsed after allogeneic bone marrow transplant.

Two analysis groups were presented for the DLBCL cohort, core and full. The core analysis (N=44) includes patients that represent the population that will move forward into the upcoming pivotal trial, which will begin in the second half of 2017. This includes patients with DLBCL (de novo and transformed from follicular lymphoma) that are ECOG Performance Status 0-1. The full analysis represents all r/r patients in the DLBCL cohort (N=55), including the 11 patients with poor performance status or niche subtypes of aggressive NHL. Both analysis groups are with conforming product, with at least one month follow up, and with a data cutoff date of May 4, 2017, for this presentation.

Key data and findings:
Core Group
Combining data across dose levels:
Overall response rate (ORR) is 86% (38/44) and the complete response (CR) is 59% (26/44).
Three-month ORR is 66% (21/32) and CR is 50% (16/32). Of three-month responders followed up at least six months, 90% (9/10) remain in response.

Early data suggest a dose response relationship at three months:
Dose level 1 (50 million cells) ORR is 58% (11/19) and CR is 42% (8/19).
Dose level 2 (100 million cells) ORR is 78% (7/9) and CR is 56% (5/9).
97% (37/38) of responding patients are alive and in follow up as of May 4, 2017.
2% (1/44) experienced severe CRS and 18% (8/44) experienced severe NT.
66% (29/44) did not experience any CRS or NT. No deaths were reported from CRS or NT.
There was one Grade 5 adverse event of diffuse alveolar damage, which the investigator assessed as related to fludarabine, cyclophosphamide, and JCAR017 treatment, occurring on day 23 in an 82-year-old subject who refused mechanical ventilation for progressive respiratory failure while neutropenic on growth factors and broad spectrum antibiotics and antifungals.

Full Dataset
Combining data across dose levels:
Best ORR is 76% (41/54) and CR is 52% (28/54).
Three-month ORR is 51% (21/41) and CR is 39% (16/41).
2% (1/55) experienced severe CRS and 16% (9/55) experienced severe NT. 60% (33/55) did not experience any CRS or NT. No deaths reported from CRS or NT.
Early data do not suggest a dose toxicity relationship at the doses tested:
Severe CRS rate is 3% (1/30) at dose level 1 and 0% (0/19) at dose level 2.
Severe NT rate is 20% (6/30) at dose level 1 and 11% (2/19) at dose level 2.
11% (6/55) received tocilizumab and 24% (13/55) received dexamethasone.
The most frequently reported treatment-emergent adverse events were neutropenia (35%), CRS (35%), and fatigue (31%).

Manufacturing
Product was available for 98% (86/88) of patients apheresed, and product that met specification was available for 89% (78/88) of patients.
About Juno’s Chimeric Antigen Receptor (CAR) and T Cell Receptor (TCR) Technologies
Juno’s CAR and TCR technologies genetically engineer T cells to recognize and kill cancer cells. Juno’s CAR T cell technology inserts a gene for a particular CAR into the T cell, enabling it to recognize cancer cells based on the expression of a specific protein located on the cell surface. Juno’s TCR technology provides the T cells with a specific T cell receptor to recognize protein fragments derived from either the surface or inside the cell. When either type of engineered T cell engages the target protein on the cancer cell, it initiates a cell-killing response against the cancer cell. JCAR014 and JCAR017 are investigational product candidates and their safety and efficacy have not been established.

On June 5, 2017 ImmunoCellular Therapeutics, Ltd. ("ImmunoCellular") (NYSE MKT: IMUC) reported the presentation of data from the phase 1 clinical trial of ICT-121 in patients with recurrent glioblastoma (Press release, ImmunoCellular Therapeutics, JUN 5, 2017, View Source [SID1234519399]). The data from the 20-patient, open-label, multi-center study show that 6 of 20 patients are alive (as of April 2017; survival ranging from 10 to 24 months), and these patients will continue to be followed. As noted in the data presentation, ICT-121 was generally safe and well tolerated. As also noted, although diversity in patient disease severity resulting from a protocol amendment to expand patient eligibility makes interpretation of survival data difficult, the results are encouraging and warrant further investigation. Pending immune response data will provide insight into the potential effectiveness of ICT-121 in inducing the formation of cytotoxic T cells targeting CD133, a cancer stem cell marker. ICT-121 is a dendritic cell-based immunotherapy that specifically targets CD133 which is overexpressed in a wide variety of solid tumors, including glioblastoma as well as non-small cell lung, colon, ovarian, pancreatic and breast cancers.

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The phase 1 data were presented by Jeremy D. Rudnick, MD, a neurologist in the Johnnie L. Cochran, Jr. Brain Tumor Center in the Department of Neurology at Cedars-Sinai, in a poster titled, "Immunological targeting of CD133 in recurrent glioblastoma: A multi-center Phase I translational and clinical study of autologous CD133 dendritic cell immunotherapy." The data were presented at the 53rd Annual Meeting of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper), taking place in Chicago.

"The preliminary findings from this phase 1 trial are encouraging, especially in light of the lethality of recurrent glioblastoma and lack of therapeutic options for patients with this disease," said Dr. Rudnick. "We look forward to continuing to follow the patients in this study, and believe that ICT-121 is a potentially promising cancer immunotherapeutic agent."

The phase 1 multi-center trial of ICT-121 targeting CD133 assesses safety and tolerability (primary endpoint) and monitors overall survival and progression-free survival (secondary endpoints). ICT-121 is comprised of autologous dendritic cells that are loaded with two HLA-A2 restricted epitopes of the CD133 antigen. After surgical resection, the HLA-A2-positive patients with recurrent glioblastoma were treated with ICT-121 once a week for 4 weeks during the induction phase and then once every 2 months during the maintenance phase until disease progression, death, ICT-121 depletion or discontinuation. In addition to safety and survival data, the phase 1 trial also assesses immune response by using an ELISpot assay and examining cytokine mRNA expression in response ICT-121 treatment.

"We are encouraged by the preliminary phase 1 results of ICT-121, which we believe underscore the potential of our DC-based approach to cancer immunotherapy," said Anthony J. Gringeri, PhD, ImmunoCellular President and Chief Executive Officer. "We are grateful for the time and effort of the patients, investigators, and staff who supported this clinical study."

About Recurrent Glioblastoma and CD-133

A defining characteristic of glioblastoma is the high incidence of tumor recurrence, which is thought to be triggered by cancer stem cells. These tumorigenic cells tend to be resistant to irradiation and chemotherapeutic agents. The target antigen, CD-133, is overexpressed in glioblastoma tumors and has been identified as a marker for cancer stem cells. Recent clinical trials suggest that the short survival time for these patients emphasizes the important unmet medical need in this disease requiring additional strategic approaches. Dendritic cell immunotherapies, such as ICT-121, could provide benefit to patients by educating their immune systems to induce the formation of cytotoxic T cells that attack tumor cells bearing the target antigen. In addition to immediate attack on tumor cells present at dosing, a long-term memory response effective against tumor recurrence might be induced. Immunotherapy, such as ICT-121, that targets cancer stem cells could be an important treatment for this disease.

On June 5, 2017 Corvus Pharmaceuticals, Inc. (NASDAQ:CRVS), a clinical-stage biopharmaceutical company focused on the development and commercialization of novel immuno-oncology therapies, reported interim safety and efficacy results from the renal cell carcinoma (RCC) and non-small cell lung cancer (NSCLC) expansion cohorts in its ongoing Phase 1/1b study (Press release, Corvus Pharmaceuticals, JUN 5, 2017, View Source [SID1234519398]). The data showed that treatment with CPI-444 as a single agent and in combination with atezolizumab (Tecentriq) resulted in anti-tumor activity in patients resistant or refractory to prior treatment with anti-PD-(L)1 antibodies and patients with PD-L1 negative tumors. CPI-444 is a selective and potent inhibitor of the adenosine A2A receptor. Atezolizumab, developed by Genentech, a member of the Roche Group, is a monoclonal antibody designed to target and bind to a protein called PD-L1 (programmed death ligand-1).

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The interim data were presented today in an oral presentation at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2017 Annual Meeting in Chicago by Lawrence Fong, M.D., Professor in Cancer Biology and Leader of the Cancer Immunotherapy Program at the Helen Diller Family Comprehensive Cancer Center at the University of California, San Francisco.

"These preliminary results from the CPI-444 clinical trial show that targeting this novel immunosuppressive pathway can lead to both anti-tumor immune responses and clinical responses in patients who have progressed on anti-PD-(L)1 therapies," said Dr. Fong. "Lung and renal cell cancer patients who do not respond to treatment with PD-(L)1 therapies typically continue to progress rapidly and have very few options to manage their disease, creating a significant unmet need in cancer therapy. These data suggest that CPI-444, both as a single agent and in combination with atezolizumab, may induce tumor regression or disease control in these difficult-to-treat populations."

"The anti-tumor activity and durability of responses and disease control seen to date are encouraging, especially in patients who are resistant/refractory to prior anti-PD-(L)1 therapy and have PD-L1 negative tumors. No therapies are currently approved that can overcome resistance to anti-PD-(L)1 therapies and few, if any, immunotherapies in development have reported benefit in the PD-1 resistant/refractory setting," said Richard A. Miller, an oncologist and co-founder, president and chief executive officer of Corvus. "In addition to our previously announced cohort expansions, based on data reported here, we have met the pre-defined criteria for the second expansion to the maximum number of 48 patients in the RCC cohort receiving combination therapy. We look forward to continuing to evaluate patients with lung and renal cell cancer enrolled in the multiple expansion cohorts, as we believe that targeting the adenosine pathway could lead to new treatment options for patients in this setting."

KEY PATIENT DEMOGRAPHIC DATA

Interim safety and efficacy data on 75 patients with RCC (n=30) or NSCLC (n=45) enrolled in the Phase 1/1b study to date were presented. Of these, 73 percent of RCC patients and 82 percent of NSCLC patients were resistant or refractory to prior therapy with anti-PD-(L)1 antibodies. Of the RCC (n=19) and NSCLC (n=28) patients with archived samples available, 95 percent and 54 percent of patients, respectively, had PD-L1 negative tumors.

KEY STUDY RESULTS IN RCC PATIENTS

An infographic accompanying this announcement is available at View Source

• Best tumor response data for RCC patients are shown in a "waterfall" plot (Figure 1). There were two confirmed partial responses (PR) out of 22 evaluable patients.

One PR was in a patient treated with single agent CPI-444 who was resistant/refractory to prior anti-PD-(L)1 therapy and was PD-L1 negative.
One PR was in an anti-PD-(L)1 treatment-naïve patient treated with combination therapy. The PD-L1 status of this patient treated in combination was not available at the time of the presentation.
The duration of PRs, which are ongoing in these two patients, exceeds eight months and three months.
• 16 patients achieved stable disease, with six of these patients experiencing minor regressions (MR). Four of the patients that achieved an MR were resistant/refractory to prior anti-PD-(L)1 therapy. The remaining patients had progressive disease or progressed before their first CT scan was obtained.

Six patients have had disease control for more than six months (range: 6-12 months), with five of these six patients continuing on therapy (three single agent, two combination).
• For RCC patients with stable disease, an analysis of tumor growth kinetics demonstrated that several patients with documented tumor growth prior to study enrollment, had stabilization or regression of their tumors while receiving treatment with CPI-444, suggesting that treatment altered the behavior of tumor growth.

KEY STUDY RESULTS IN NSCLC PATIENTS

An infographic accompanying this announcement is available at View Source

• Best tumor response data for NSCLC patients are shown in a "waterfall" plot (Figure 2). There were two partial responses (PR) out of 34 evaluable patients.

One confirmed PR was in a patient treated with combination therapy who was resistant/refractory to prior anti-PD-(L)1 therapy and is PD-L1 negative. The PR is ongoing at six months.
One unconfirmed PR is in a patient who received the combination, was resistant/refractory to prior anti-PD-(L)1 therapy, is PD-L1 positive, and is ongoing at two months.
• 22 patients achieved stable disease. Four of the stable disease patients, all of whom were were resistant/refractory to prior anti-PD-(L)1 therapy, had MRs. The remaining patients had progressive disease or progressed before their first CT scan was obtained.

• Four patients with NSCLC, three of whom were resistant/refractory to prior anti-PD-(L)1 therapy, experienced disease control exceeding six months (two single agent, two combination). All of the patients continue on therapy.

SAFETY DATA
CPI-444 continues to be well tolerated to date, with observed adverse events similar to previous reports. For single-agent CPI-444 cohorts, the following Grade 1 and 2 adverse events occurred in 5 percent or more of patients: fatigue, nausea, pruritis, constipation, dizziness, hypertension and fever. For combination therapy cohorts, the following Grade 1 and 2 adverse events occurred in 5 percent or more of patients: fatigue, nausea, pruritis, rash and increase in liver enzymes. In the combination cohort, one patient developed reversible Grade 3 immune-related toxicities.

PHASE 1/1B TRIAL DESIGN
The Phase 1/1b trial is designed to select the dose, assess the safety and examine the activity of CPI-444 as a single agent and in combination with Genentech’s atezolizumab, an anti-PD-L1 antibody, in multiple histologies known to be sensitive to immuno-oncology agents. Patients with non-small cell lung cancer, melanoma, renal cell cancer, triple-negative breast cancer (TNBC), MSI-H colorectal cancer, head and neck cancer, bladder cancer and prostate cancer who have failed standard therapies are eligible. The efficacy endpoints of the study are response rate and disease control rate, which is defined as complete response, partial response (reduction of >30 percent tumor volume) or stable disease (change in tumor volume of between 20 percent growth of tumor and 30 percent reduction of tumor volume). Patients with minor tumor regressions are those with changes in tumor volume of 0 to ≤30 percent reduction in tumor volume. Patients are treated until disease progression or evidence of Grade 3 or 4 toxicity.

The dose-selection part of the study included four cohorts of 12 patients each (N=48) – three cohorts treated with single agent CPI-444 (100 mg twice daily for 14 days; 100 mg twice daily for 28 days; 200 mg once daily for 14 days) and one cohort treated with the combination (CPI-444 50 mg or 100 mg twice daily for 14 days combined with atezolizumab). A treatment cycle is 28 days. Based on biomarker analyses showing sustained, complete blockade of the adenosine A2A receptor in peripheral blood lymphocytes, and evidence of immune activation in circulating lymphocytes, an optimum single agent and combination dose of 100 mg twice a day for 28 days was selected for the second part of the study. As defined in the protocol, patients in the dose-selection stage of the trial receiving the dose and schedule selected for evaluation in the second part of the study are included in the disease-specific cohort efficacy analysis.

The second part of the study is evaluating CPI-444 as a single agent in five disease-specific cohorts (NSCLC, melanoma, RCC, TNBC and a category of "other" that includes MSI-H colorectal cancer, bladder cancer and prostate cancer) and CPI-444 in combination with atezolizumab in five additional matched disease-specific cohorts. Each of the 10 cohorts is initially enrolling 14 patients, but may be expanded based on efficacy. To date, RCC and NSCLC, both single agent and combination cohorts, have met the initial criteria for expansion to 26 patients. Recently, the combination cohort of patients with renal cell cancer met the second criteria for expansion to 48 patients.