Immunocore Presents New IMCgp100-102 Data that Show Durable Response and Robust Overall Survival Rate in Patients with Metastatic Uveal Melanoma

On June 4, 2018 Patients with metastatic uveal melanoma (mUM) treated with IMCgp100 continued to experience a durable tumour response with a median follow up of 19.1 months, without yet reaching median overall survival (OS), according to new Phase I research to be reported at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in Chicago.2 IMCgp100 is the wholly-owned, lead programme from Immunocore Limited, a leading T-cell receptor (TCR) company focused on delivering first-in-class biological therapies that transform lives (Press release, Immunocore, JUN 4, 2018, View Source [SID1234527140]).

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!

Although rare, uveal melanoma is the most common form of adult eye cancer.3 When it metastasises beyond the eye, less than half of patients will survive for one year.4 Of the 19 HLA-A*0201+ patients enrolled in Phase I of the Phase I/II dose escalation trial, 17 were evaluated for efficacy. Among these patients, treatment with IMCgp100 was associated with an objective response rate of 18% (90% confidence interval [4,30]) and a one-year overall survival rate of 74% (95% confidence interval [48,88]) at the time of data cut-off.2

"Survival rates in uveal melanoma have remained largely unchanged for decades, and it is difficult to treat once it advances to metastatic disease," said Dr. Takami Sato, Department of Medical Oncology, Kimmel Cancer Center, Thomas Jefferson University and lead investigator. "These data provide compelling evidence that IMCgp100 may offer hope to this underserved patient population."

Additional exploratory survival analyses also indicated prolonged OS was associated with a number of pharmacodynamic outcomes, including lymphocyte trafficking, providing encouraging evidence supporting the proposed mechanism of action of IMCgp100.2

"Immunocore is focused on transforming the lives of patients with some of the most challenging diseases, such as metastatic uveal melanoma, for which there is currently no standard of care," said Andrew Hotchkiss, Chief Executive Officer at Immunocore. "Although these are early findings, we are encouraged by the emerging clinical data and focused on advancing our pivotal trials."

The most common adverse events in the Phase I arm included pruritus (severe itching of the skin; 90%), pyrexia (fever) and fatigue (84%), and hypotension (74%).2 Dose limiting toxicities were observed in 3 patients; all were reversible abnormalities in liver function tests (Grade 3 or 4 ALT/AST changes). There were no IMCgp100-related AEs that resulted in discontinuation or death.2

About Metastatic Uveal Melanoma
Uveal melanoma is an aggressive form of melanoma which affects the eye, with a poor prognosis and no standard of care.5 Although it is the most common primary intraocular malignancy in adults,3 the diagnosis is rare, with approximately 4,000 new patients diagnosed globally each year (1,500 cases/year in US).1 Up to 50% of people with uveal melanoma will eventually develop metastatic disease.5,6 When the cancer spreads beyond the eye, only approximately 40% of patients will survive for one year.4

About the IMCgp100-102 Phase I/II Trial
In this study, IMCgp100 is administered on a weekly basis with an intra-patient escalation dosing regimen. The dose escalation portion of the study has been completed, which identified the recommended Phase II intra-patient dose. The Phase II portion of the study is ongoing evaluating both the safety and efficacy in patients with metastatic uveal melanoma. The currently enrolling cohort is assessing IMCgp100 in patients who have experienced disease progression after 1 or 2 prior lines of therapy, which may include up to 1 line of liver directed therapy. Approximately 150 patients will be enrolled in the Phase II portion and the estimated enrolment completion date is September 2019.

About the IMCgp100 Programme
IMCgp100 is a novel bi-specific biologic T cell redirection therapy that specifically targets the melanoma-associated antigen gp100, and which is now in pivotal studies for mUM. IMCgp100 was granted Orphan Drug Designation by the US Food and Drug Administration in 2016 and Promising Innovative Medicine designation under UK Early Access to Medicines Scheme in 2017. For more information about enrolling IMCgp100 clinical trials for metastatic uveal melanoma, please visit ClinicalTrials.gov (NCT02570308, NCT03070392).

About ImmTAC Molecules
Immunocore’s proprietary TCR (T Cell Receptor) technology generates a novel class of bi-specific biologics called ImmTAC (Immune mobilising monoclonal TCRs Against Cancer) molecules that enable the immune system to recognise and kill cancerous cells. ImmTAC molecules are based on synthetic, soluble TCRs engineered to recognise intracellular cancer antigens with ultra-high affinity and selectively kill cancer cells via an anti-CD3 immune-redirecting effector function. ImmTAC molecules can access up to nine-fold more target antigens than typical antibody-based approaches, including monoclonal antibodies. Based on the demonstrated mechanism of T cell infiltration into human tumours, the ImmTAC mechanism of action holds the potential to tackle solid "cold" low mutation rate tumours, the majority of tumours that do not adequately respond to currently available immunotherapies.

“Pharmacodynamics and Genomic Profiling of Patients Treated With Cabiralizumab + Nivolumab Provide Evidence of On-Target Tumor Immune Modulations and Support Future Clinical Applications”


On June 4, 2018, a poster titled "Pharmacodynamics and Genomic Profiling of Patients Treated With Cabiralizumab + Nivolumab Provide Evidence of On-Target Tumor Immune Modulations and Support Future Clinical Applications" was presented at the 2018 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting (Presentation, Five Prime Therapeutics, JUN 4, 2018, View Source [SID1234527139]).

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!

Adaptimmune Announces First Patient to Receive One Billion Target Cell Dose after Positive Safety Data from Pilot Study with MAGE-A4 SPEAR T-cells

On June 4, 2018 Adaptimmune Therapeutics plc (Nasdaq:ADAP), a leader in T-cell therapy to treat cancer, reported that the independent safety review committee has recommended dose escalation in the MAGE-A4 basket study, based on an acceptable safety profile in three patients dosed with 100 million cells (Press release, Adaptimmune, JUN 4, 2018, View Source;p=irol-newsArticle&ID=2352953 [SID1234527138]). The company will start treating patients with the target dose of one billion transduced MAGE-A4 SPEAR T-cells in the ongoing basket 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!

In addition, after confirming expression levels for MAGE-A4 from synovial sarcoma and myxoid/round cell liposarcoma (MRCLS) tumor samples, Adaptimmune has amended the study to add these two indications to the ongoing basket study, which already includes bladder, melanoma, head & neck, esophageal, gastric, ovarian, and non-small cell lung (NSCLC) cancers. Screening of patients with synovial sarcoma and MRCLS is ongoing.

"Today’s announcement that we are dosing patients with one billion cells, which we believe is a potentially therapeutic dose based on data from NY-ESO, means that we are on target to get response data in our MAGE-A4 study, to which we have added two solid tumor indications, in 2018," said James Noble, Adaptimmune’s Chief Executive Officer. "This follows the earlier announcement that pilot studies in our other program, MAGE-A10, have also moved to the one billion cells dose."

Target validation, investigating antigen expression in tumor samples, has been a key focus for Adaptimmune to understand the breadth of patients that have the potential to benefit from SPEAR T-cell treatment. Data from monitoring target antigen expression levels across literature, databases, and tumor samples indicate that MAGE‑A4 is expressed in both synovial sarcoma and MRCLS. Evaluation of expression of target antigens, including MAGE-A4, in other cancers will continue.

The MAGE-A4 basket study is a Phase 1, open-label, pilot study to evaluate the safety and efficacy of Adaptimmune’s SPEAR T-cells targeting MAGE-A4 in cancers in which MAGE-A4 is expressed.

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).

CytomX Therapeutics Presents Preliminary Clinical Proof-of-Concept Data from Probody™ Platform and CX-072 at 2018 ASCO Annual Meeting

On June 4, 2018 CytomX Therapeutics, Inc. (Nasdaq:CTMX) a clinical-stage oncology-focused biopharmaceutical company pioneering a novel class of investigational antibody therapeutics based on its Probody therapeutic technology platform, reported that preliminary clinical results from two arms of the PROCLAIM (PRObody CLinical Assessment In Man) module, PROCLAIM-072 (Press release, CytomX Therapeutics, JUN 4, 2018, View Source [SID1234527137]). PROCLAIM-072 is an ongoing Phase 1/2 trial evaluating CX-072, a Probody therapeutic targeting PD-L1, as monotherapy and in combination with Yervoy (ipilimumab) or Zelboraf (vemurafenib) in patients with advanced, unresectable solid tumors. Data from the CX-072 monotherapy arm and ipilimumab combination arm were presented today in two posters as part of the Developmental Therapeutics—Immunotherapy Session at the 2018 Annual Meeting of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) in Chicago, Illinois.

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!

"These first clinical results mark a major milestone for CytomX as we advance our Probody platform and introduce a fundamentally new approach to antibody therapeutic drug development," said Sean McCarthy D.Phil., president and chief executive officer of CytomX Therapeutics. "The findings presented today show that our lead wholly-owned program, the PD-L1 targeting Probody therapeutic, CX-072, has the potential to become a new centerpiece of combination cancer therapy. These preliminary results suggest that CX-072 as monotherapy and in combination with ipilimumab has a favorable safety profile and encouraging antitumor efficacy in late-stage, heavily pretreated cancer patients. Moreover, these clinical data check important boxes for the development of our core platform technology by showing that CX-072 remains stable in circulation over extended periods of dosing and elicits anti-tumor effects within the tumor microenvironment. Based on these initial results, we have initiated multiple monotherapy expansion cohorts to further explore the safety and efficacy of this potentially differentiated PD-L1 inhibitor."

Preliminary Results of the First-In-Human, Dose-Finding PROCLAIM-072 Trial of the PD-L1 Probody Therapeutic CX-072 as Monotherapy in Patients with Advanced Solid Tumors

Session: Developmental Therapeutics—Immunotherapy (Poster #285)
Presenter: Karen A. Autio, M.D., MSc., Memorial Sloan Kettering Cancer Center

The primary objectives of this first-in-human, dose-escalation, monotherapy arm are to assess safety and tolerability, including determination of the maximum tolerated dose (MTD) and the dose-limiting toxicity (DLT) of CX-072 as monotherapy. At the completion of escalation, the arm had enrolled 22 patients, with an average of four prior anti-cancer treatments in a variety of tumor types for which no anti-PD-1 or anti-PD-L1 agents are available for their disease. Patients received escalating doses of CX-072 from 0.03 mg/kg to 30 mg/kg. Enrollment is complete and patient follow-up is ongoing.

Monotherapy Well Tolerated

The maximum tolerated dose (MTD) was not reached. As of an April 20, 2018 data cutoff, results showed that the administration of monotherapy CX-072 was well tolerated with the majority of treatment-related adverse events (TRAEs) as Grade 1/2. Grade 3/4 TRAEs were reported in two patients: neutropenia and thrombocytopenia in a patient with thymic cancer (3 mg/kg) and transaminase elevation in a patient with breast cancer (30 mg/kg). Both events were successfully managed with therapeutic intervention including steroids and discontinuation of CX-072.

Evidence of Activity

As of an April 20, 2018 data cutoff, results showed that among 20 evaluable patients who received CX-072, objective responses by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, a commonly used guideline for evaluating tumors, were observed in 3 (15%) patients: thymoma (unconfirmed PR (uPR); 3 mg/kg), PD-L1 negative TNBC (confirmed PR; 10 mg/kg) and cervical cancer (uPR; 10 mg/kg) (all partial responses (PR)). Stable disease was observed in 8 patients (40%) for a disease control rate of 55%. Decreased target lesions were observed in 42% (8/19) of all evaluable patients with measurable disease at baseline and in 60% (6/10) of the subset of patients who received > 3 mg/kg of CX-072. Two of the responders were still on treatment (8 months each) at the time of the data cutoff.

Evidence of Probody Platform Performance

Results from a preliminary single-dose pharmacokinetic analysis of single-agent CX-072 suggest that, as designed, CX-072 circulates predominantly as the intact masked prodrug across all dose levels. Further, CX-072 is only minimally influenced by target mediated drug disposition at low doses, suggesting that masking is effective in blocking interaction with PD-L1 in the periphery.

Based on these preliminary safety, efficacy and translational data, further evaluation of CX-072 monotherapy (10 mg/kg every two weeks) is now underway in 8 expansion cohorts in a variety of cancer types.

Preliminary Interim Results of the First-In-Human, Dose-Finding PROCLAIM-072 Trial of the PD-L1 Probody Therapeutic CX-072 in Combination with Ipilimumab in Patients with Advanced Solid Tumors

Session: Developmental Therapeutics—Immunotherapy (Poster #286)
Presenter: Rachel E. Sanborn, M.D., Earle A. Chiles Research Institute, Providence Cancer Center

The primary objectives of this ongoing arm of the study are to assess safety and tolerability, and to determine the MTD and DLT of CX-072 when administered in a concomitant combination schedule with ipilimumab. At the April 20, 2018 data cutoff, the study had enrolled 16 immunotherapy naïve patients who had received an average of four prior anti-cancer treatments in a variety of tumor types for which no anti-PD-1 or PD-L1 agents were available for their disease. Patients received the combination ipilimumab (3 mg/kg) and CX-072 (escalating doses of 0.3 mg/kg to 10 mg/kg) every three weeks for four cycles followed by monotherapy CX-072 every two weeks.

Combination with Ipilimumab Well Tolerated

As of the April 20, 2018 data cutoff date, the MTD had not yet been reached and no new safety signals were observed beyond those expected for each component of the ipilimumab plus CX-072 combination. The majority of TRAEs were Grade 1/2. Of the 16 treated patients, 5 (31%) reported a Grade 3/4 TRAE, a rate similar to that reported previously for 3 mg/kg ipilimumab monotherapy1. These events included: Grade 3 colitis (n=1), Grade 3 dyspnea/pneumonitis (n=1), Grade 3 headache/Grade 3 hyponatremia (n=1), and Grade 3 amylase/Grade 4 lipase (n=1)2. A dose limiting toxicity of Grade 3 dyspnea was reported in one patient. The study is still ongoing with enrollment and dose escalation continuing.

Evidence of Activity

As of an April 20, 2018 data cutoff, results also showed that among 12 evaluable patients who received ipilimumab (3 mg/kg) combined with CX-072 (0.3 to 10 mg/kg), 3 (25%) achieved objective responses by RECIST v1.1, including patients with: anal cancer (confirmed complete response (CR); 0.3 mg/kg CX-072), testicular cancer (uPR; 1 mg/kg CX-072) and cancer of unknown primary (uPR; 3 mg/kg CX-072). Stable disease was observed in 8% of patients for a disease control rate of 33%. All 3 of the responders remained on treatment (10, 6 and 5 months, respectively) at the data cutoff.

Preliminary Single-Dose Clinical Pharmacokinetics of an anti-PD-L1 Probody Therapeutic in Cancer Patients
ASCO Supplement of the Journal of Clinical Oncology [J Clin Oncol 36, 2018 (suppl; abst 214558)]. (Abstract #e14558)

Preliminary pharmacokinetic clinical data showed that single-agent, single-dose CX-072 behaved as designed and circulated predominantly as the intact antibody prodrug and is only minimally affected by target-mediated drug disposition, consistent with being effectively masked in circulation.

Conference Call and Webcast

CytomX will host a conference call and live webcast with slides today, Monday, June 4, 2018, beginning at 5:00 p.m. CT/ 6:00 p.m. ET to discuss these data presentations. This event can be accessed in three ways:

From the CytomX website: View Source Please access the website 15 minutes prior to the start of the call to download and install any necessary audio software.

By telephone: Participants can access the call by dialing 1-877-809-6037 (United States) or 1-615-247-0221 (International) referencing Conference ID 4294667.

By replay: A replay of the webcast will be located under the Investor Relations section of CytomX’s website approximately two hours after the conclusion of the live call and will be available for 30 days following the call.
About PROCLAIM

PROCLAIM (Probody Clinical Assessment In Man) is an international umbrella program designed to evaluate CytomX’s Probody therapeutics. The first module is the PROCLAIM-CX-072 clinical program, an open-label, dose-finding Phase 1/2 trial evaluating CX-072 as monotherapy and in combination with Yervoy (ipilimumab) or Zelboraf(vemurafenib) in patients with metastatic or locally advanced unresectable solid tumors or lymphomas. CytomX aims to achieve three goals as part of the PROCLAIM-072 clinical trial:

Tolerability: Demonstrate that CX-072 is well tolerated in patients and potentially improves safety, particularly in the combination setting.
Anti-cancer activity: Demonstrate initial evidence of CX-072’s anti-cancer activity as monotherapy and in combination.
Translational program and Probody platform proof-of-concept: Explore mechanistic aspects of Probody activity in patients as observed in preclinical models.

FDA Grants Cellectis IND Approval for UCART22 in B-ALL

On June 4, 2018 Cellectis (Euronext Growth: ALCLS – Nasdaq: CLLS), a clinical-stage biopharmaceutical company focused on developing immunotherapies based on gene-edited allogeneic CAR T-cells (UCART), reported that the U.S. Food and Drug Administration (FDA) has approved the Company’s Investigational New Drug (IND) application to initiate a Phase 1 clinical trial for UCART22, Cellectis’ second wholly controlled TALEN gene-edited product candidate, for the treatment of B-cell acute lymphoblastic leukemia (B-ALL) in adult patients (Press release, Cellectis, JUN 4, 2018, View Source [SID1234527136]).

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!

UCART22 is the 3rd allogeneic, off-the-shelf, gene-edited CAR T-cell product candidate approved by the FDA for clinical trials in the U.S., following UCART19 (exclusively licensed to Servier and under joint development agreement between Servier and Allogene), and Cellectis’ UCART123. Cellectis intends to begin the UCART22 Phase 1 study in the second half of 2018. The research for UCART22 will be led by Dr. Nitin Jain, Assistant Professor, and Prof. Hagop Kantarjian, Chairman in the Department of Leukemia and University Chair in Cancer Medicine, at The University of Texas MD Anderson Cancer Center in Houston.

"The FDA’s approval of Cellectis’ UCART22 IND application for the treatment of B-ALL puts us one step closer to providing patients in need with a better access to an effective drug candidate for such a rare, devastating disease," said Prof. Stéphane Depil, Senior Vice President, Research & Development, and Chief Medical Officer, Cellectis. "With this opportunity, Cellectis is well-positioned to further its work in the off-the-shelf gene-editing space, in the hope of helping patients to beat B-ALL in the near future."

"Given that Cellectis is leading the allogeneic CAR-T approach across today’s medical landscape – first, with the FDA’s IND approval for UCART123 last year and now, with approval of UCART22 IND – we are eager to bring an innovative therapy to the market for patients who are suffering from B-ALL everywhere," added Stephan Reynier, Chief Regulatory and Compliance Officer, Cellectis. "The bottom line is that patients are in dire need of effective, affordable and easily accessible treatments across the board, and our off-the-shelf product candidates aim to do just that."

About UCART22

UCART22 is an allogeneic, off-the-shelf gene-edited T-cell product candidate designed for the treatment of B-ALL. Like CD19, CD22 is a cell surface antigen expressed from the pre-B-cell stage of development through mature B-cells. CD22 expression occurs in more than 90% of patients with B-ALL.[1]

UCART22 clinical trial is a Phase 1, open label dose-escalation and dose-expansion study to evaluate the safety, expansion, persistence and clinical activity of UCART22 (allogeneic engineered T-cells expressing anti-CD22 chimeric antigen receptor) in patients with relapsed or refractory CD22+ B-cell acute lymphoblastic leukemia (B-ALL). Dose level 1 to be administered is 1×105 UCART22 cells per kilogram. Dose levels 2 and 3 are respectively at 1×106 and 5×106.

ALL is a heterogeneous hematologic disease characterized by the proliferation of immature lymphoid cells in the bone marrow, peripheral blood, and other organs. It can start either with early B-cells or T-cells at different stages of maturity. The American Cancer Society’s estimates for acute lymphocytic leukemia (ALL) in the United States for 2018 (including both children and adults) are about 5,960 new cases of ALL and about 1,470 deaths from ALL. Approximately 85% of ALL cases involve precursor B-cells (B-ALL).

The manufacturing process of Cellectis’ allogeneic CAR T-cell product line, Universal CARTs or UCARTs, yields frozen, off-the-shelf, non-alloreactive engineered CAR T-cells. UCARTs are meant to be readily available CAR T-cells for a large patient population. Their production is industrialized with defined pharmaceutical release criteria