On June 4, 2021 Candel Therapeutics, Inc., a late clinical stage biopharmaceutical company developing novel oncolytic viral immunotherapies, reported initial results from an ongoing Phase 1 clinical trial of its oncolytic virus, CAN-3110, in patients with high-grade glioma (HGG) that has recurred after initial treatment (Press release, Candel Therapeutics, JUN 4, 2021, View Source [SID1234583579]). The data are presented today in an Oral Abstract Session of the Clinical Science Symposium at the 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting.

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"This is the first clinical trial of a novel oncolytic HSV engineered to selectively express ICP34.5 in tumor cells, leading to tumor-specific cell death. This novel oncolytic viral immunotherapy has been shown to be well tolerated with primarily low grade, and manageable side effects"

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Highlights from the Oral Abstract Session of the Clinical Science Symposium at ASCO (Free ASCO Whitepaper) 2021

An ongoing Phase 1 study is evaluating the safety and activity of CAN-3110, an engineered replication-competent herpes simplex virus (HSV) oncolytic viral immunotherapy, in patients with HGG who have experienced disease progression following prior treatment with standard of care therapies. As of the data cutoff date of April 21, 2021:

30 patients were evaluable for safety.
Nine dose levels ranging from 1×106 to 1×1010 plaque forming units (PFU) were administered.
No dose-limiting toxicity was observed. The maximum administered dose was 1×1010 PFU.
CAN-3110 was well-tolerated and all but one adverse events (AEs) were Grade 1 or 2.
A preliminary Kaplan-Meier estimate of median overall survival was 11.7 months.
All patients have been treated for more than 12 months.
One patient who responded for over a year, a 56-year-old male with multifocal glioblastoma, demonstrated a significant reduction in both an injected and an uninjected lesion, suggesting an abscopal effect of CAN-3110.
An additional 12 patients have been enrolled into a dose expansion arm of the trial.
"CAN-3110 has demonstrated a significant number of durable responses in patients with high-grade glioma who experienced disease progression following prior standard of care therapy," said Antonio Chiocca, MD, PhD, FAANS, Neurosurgeon-in-Chief and Chairman, Department of Neurosurgery at Brigham and Women’s Hospital. "The results of this first-in-human study are encouraging as they demonstrate a median overall survival that was substantially longer than the six to nine months typically observed for these patients as well as a favorable safety profile."

"This is the first clinical trial of a novel oncolytic HSV engineered to selectively express ICP34.5 in tumor cells, leading to tumor-specific cell death. This novel oncolytic viral immunotherapy has been shown to be well tolerated with primarily low grade, and manageable side effects," said Paul Peter Tak, MD, PhD, FMedSci, President and Chief Executive Officer of Candel Therapeutics. "There are few treatment options for patients with high-grade glioma whose tumors progress following initial surgery and chemoradiation. We are encouraged by the duration of the responses observed to date in this patient population given the extremely limited treatment options. Based on these data, we are excited to advance this innovative agent into further clinical trials."

Details of the presentation are as follows:

Abstract Title: First-in-human CAN-3110 (ICP34.5 expressing HSV-1 oncolytic virus) in patients with recurrent high-grade glioma

Presenter: Dr. E. Antonio Chiocca

Session Date and Time: The presentation is available to ASCO (Free ASCO Whitepaper) attendees beginning June 4, 2021 at 9 AM EDT/ 6 AM PDT and has been reposted to the Candel Therapeutics website at www.candeltx.com/news

Abstract Link: View Source

Session Title: CNS Targeting: From Delivery to Biomarker Assessment

Abstract Number: 2009

About CAN-3110

CAN-3110 is an HSV replication-competent oncolytic virus engineered to enhance selective killing of malignant cells while sparing healthy normal neighboring cells. CAN-3110 selectively expresses ICP34.5, a key gene in HSV replication, in tumor cells that overexpress nestin, a cytoskeletal protein. Nestin is highly expressed in glioma cells and other tumor tissue but is absent in the healthy adult brain.

Candel is evaluating the effects of treatment with CAN-3110 for recurrent glioblastoma. For more information on this clinical study, please visit View Source

On June 4, 2021 InnoCare (HKEX: 09969), a leading biopharmaceutical company focusing on cancer and autoimmune diseases, reported the latest clinical data for the pan-FGFR inhibitor gunagratinib today at the 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) annual meeting (Press release, InnoCare Pharma, JUN 4, 2021, View Source [SID1234583597]). This is the first time InnoCare has presented gunagratinib’s clinical data at an international academic conference, showing good safety and tolerability.

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Updated Results from the Phase I Study of a highly selective irreversible FGFR inhibitor ICP-192 (gunagratinib) for patients with advanced solid tumors with abnormal FGFR gene

Abstract Number: 4092

ICP-192 (gunagratinib), developed by InnoCare Pharma, is a novel pan-FGFR (fibroblast growth factor receptors) inhibitor that potently and selectively inhibits FGFR activities irreversibly by covalent binding. Preclinical data showed that gunagratinib overcomes the acquired resistance to the first-generation reversible FGFR inhibitors.

Gunagratinib is currently in clinical phase I/II. The safety and tolerability as well as pharmacokinetics/pharmacodynamics (PK/PD) of gunagratinib were evaluated in patients with advanced solid tumors, and the preliminary anti-tumor activity was evaluated by RECIST1.1 in patients with FGF/FGFR gene aberrations.

As of February 2021, a total of 30 patients had received the treatment of gunagratinib. Gunagratinib performed well in safety and tolerance, the maximum tolerated dose (MTD) had not been reached. Among the 12 patients with FGF/FGFR gene aberrations who have completed at least one tumor assessment, the overall response rate (ORR) was 33.3%, including 1 patient (8.3%) of cholangiocarcinoma with complete response (CR) and 3 patients (25%) with partial response (PR), 7 patients achieved SD. The disease control rate (DCR) was 91.7%.

Professor Ye Guo, the Deputy Director of Oncology Medical Department of Shanghai Oriental Hospital and the Director of Clinical Center for PhaseⅠsaid, "Gunagratinib is safe and well-tolerated in patients with advanced solid tumors. Anti-tumor activity was demonstrated in patients with FGF/FGFR geneaberrations in multiple tumor types, including cholangiocarcinoma. Better response is expected with the increase of treatment durations."

The 2021 ASCO (Free ASCO Whitepaper) Annual Meeting will be held online from June 4th to 8th, 2021. The ASCO (Free ASCO Whitepaper) annual meeting is the most important and professional academic event in the global oncology field, which will showcase the international cutting-edge clinical oncology research results and tumor treatment technologies.

On June 4, 2021 Immutep Limited (ASX: IMM; NASDAQ: IMMP) ("Immutep" or "the Company"), a biotechnology company developing novel LAG-3 related immunotherapy treatments for cancer and autoimmune disease, announces new interim data from its Phase II TACTI-002 study (also designated KEYNOTE-798) with a data cut-off date of 16 April 2021. The data will be presented in two poster presentations by Dr Tim Clay, Investigator, St John of God Subiaco Hospital, Perth, Australia and Dr Irene Brana, Investigator, Vall d’Hebron Institute of Oncology, Barcelona, Spain at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper)’s (ASCO) (Free ASCO Whitepaper) 2021 Annual Meeting in on-demand sessions available from 9 am on 4 June 2021, US Eastern Time at this year’s virtual conference. The posters will also be made available on Immutep’s website from that time at:

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TACTI-002 is being conducted in collaboration with Merck & Co., Inc., Kenilworth, NJ, USA (known as "MSD" outside the United States and Canada). The study is evaluating the combination of Immutep’s lead product candidate eftilagimod alpha ("efti" or "IMP321") with MSD’s KEYTRUDA (pembrolizumab) in up to 183 patients with non-small cell lung cancer (NSCLC) in 1st and 2nd line (Parts A and B, respectively) or 2nd line head and neck squamous cell carcinoma (HNSCC, Part C).

Immutep CSO and CMO, Dr Frederic Triebel said: "As more and more industry focus is on LAG-3 therapies and it is in the spotlight of this year’s ASCO (Free ASCO Whitepaper), we are very pleased to be reporting such robust and exciting results from our TACTI-002 study of efti in combination with pembrolizumab. We are seeing nearly 50% of the evaluable 1st line NSCLC patients responding to the therapy, as scored by a blinded independent central review committee, with responses in all PD-L1 subgroups and a favourable median PFS. Overall, the NSCLC patients receiving this 1st line therapy are living 8.2 months without their disease progressing, a promising improvement for a chemo-free 1st line regimen. In effect, we are seeing an improvement in patient outcomes compared with that historically seen with anti-PD-1 monotherapy but with a similar safety profile and, also, comparable results in terms of ORR and PFS to chemo + anti-PD-1 combination therapy but, importantly, with a longer duration of response and lower toxicity."

Investigator, A/Prof Tim Clay, St John of God Subiaco Hospital, Perth, Australia said: "The median PFS of 8.2 months in 1st line NSCLC patients is very encouraging compared to historical studies where pembrolizumab has been given as monotherapy in comparable patient groups. There remains a great need for more effective chemotherapy free regimens in the treatment of NSCLC. These data are exciting and as a result, we will be expanding recruitment with 74 additional patients for Part A."

Investigator, Dr Irene Brana, Vall d’Hebron Institute of Oncology, Barcelona, Spain, said: "The sustained and durable responses reported in 2nd line HNSCC patients are improving as TACTI-002 progresses, with about 14% of patients now benefiting from a complete disappearance of all their tumour lesions. Responses are particularly good in PD-L1 expressing patients (CPS ≥ 1) where an ORR of 45.8% is reported. The strength of these results validates the decision to explore the combination of efti and pembrolizumab in a new Phase IIb study, TACTI-003 in 1st line HNSCC patients which is starting in the coming months."

Table 1 – TACTI-002 Interim ORR Results for Part A and C (data cut-off date: 16 April 2021)

Part A
1st line NSCLC1 Part C
2nd line HNSCC2
Tumour Response
Best Overall Response (BOR) per iRECIST Stages 1 & 2
N (%)
Total N=36 Stage 1 & 2
N (%)
Total N=37
Complete Response (CR) 2 (5.6) 5 (13.5)
Partial Response (PR) 13 (36.1) 6 (16.2)
Stable Disease (SD) 10 (27.8) 3 (8.1)
Progressive Disease (PD) 6 (16.7) 17 (45.9)
Not Evaluable 5 (13.9) 6 (16.2)
Disease Control Rate (DCR) 25 (69.4) 14 (37.8)
Objective Response Rate (ORR) 15 (41.7) 11 (29.7)
ORR in evaluable pts 15 (48.4), N=31 11 (35.5), N=31
Key Findings

1st line NSCLC – Part A

Sustained and durable responses: 15 patients with responses giving an ORR of 41.7% on an intention-to-treat basis and 48.4% in evaluable patients, as assessed by blinded independent committee read
None of the patients with a confirmed response progressed within 6 months and the median duration of response (DoR) is currently estimated to be more than 13 months in patients unselected for PD-L1 expression
2/36 (5.6%) patients had a Complete Response (complete disappearance of tumour lesions) and 23/36 (63.9%) of patients had a target lesion decrease (includes the 2 CRs)
Durable responses observed in all PD-L1 subgroups as assessed by local investigator read,3 for example:
ORR in the ≥ 1% PD-L1 subgroup was 44.0% (11/25)
ORR in the < 50% PD-L1 subgroup was 31.6% (6/19)
ORR in the ≥ 50% PD-L1 subgroup was 53.8% (7/13)
Median overall PFS is 8.2 months in patients unselected for PD-L1 expression, as assessed by local investigator read. This is very promising for a chemo-free 1st line regimen. Median PFS increases to 11.8 months in the ≥ 50% PD-L1 subgroup and median PFS in the < 1% PD-L1 subgroup is 4.1 months
Conclusion: The data presented for 1st line NSCLC is very encouraging and will be broadened by the ongoing recruitment in this patient population to form a solid basis for late-stage clinical development.

2nd line HNSCC – Part C

11 patients with responses giving an ORR of 29.7% on an intention-to-treat basis and 35.5% in evaluable patients
Durable responses with now 5 patients (13.5%) having a Complete Response. So far median duration of response is not yet reached. None of the patients with a response progressed within 6 months
In patients unselected for PD-L1 expression, median PFS is 2.1 months and median OS is 12.6 months
In patients in PD-L1 CPS ≥ 1 subgroup (N=24), ORR is 45.8%, median PFS is 4.1 months, and median OS is 12.6 months
Conclusion: The 2nd line HNSCC data is mature and continues to be very encouraging and forms an excellent basis to move into the 1st line HNSCC indication via Immutep’s randomised Phase IIb TACTI-003 study which is expected to start in mid-2021.

2nd line NSCLC – Part B
Stage 1 results were reported in November 2020 at SITC (Free SITC Whitepaper) and Overall Survival is trending favourably. Stage 2 recently opened for patient enrolment and combined results from Stages 1 & 2 are expected to be reported later this year.

Safety
The combination treatment continues to be safe and well tolerated with no new safety signals reported thus far.

Recruitment Update
Trial recruitment continues to progress well, with 127 patients out of up to 183 already participating at 12 clinical sites across Australia, Europe, the UK and US. At present, recruitment is ongoing for the expansion stage of Part A and Stage 2 of Part B.

Recruitment details for each Part of the trial are shown below and are current as at 1 June 2021.

Table 2 – TACTI-002 Recruitment (as at 1 June 2021)

Stage 1 (N)
Actual / Target Stage 2 (N)
Actual / Target Recruitment
Status Expansion Stage
Actual / Target
Part A (1st line NSCLC) 17/17 19/19 EXPANDED 23/74
Part B (2nd line NSCLC) 23/23 6/13 RECRUITING
Part C (2nd line HNSCC) 18/18 21/194 COMPLETE
Next Results
Immutep currently expects to report further interim data from Part A, final data from Part C, and new results from Stages 1 & 2 of Part B in 2H calendar year 2021 or early calendar year 2022.

Webcast Details
Immutep will present this data in a global webcast for investors. Details are as follows:

Date & Time:

Thursday, 10 June 2021, at 7:00 am Australian Eastern Daylight Time (AEDT) (Wednesday, 9 June, at 5:00 p.m. U.S. ET)

Register:

View Source

Questions:

Investors are invited to submit questions in advance via [email protected].

A replay of the webcast will also be available at www.immutep.com from the day after the event.

About the TACT-002 Trial
TACTI-002 (Two ACTive Immunotherapies) is being conducted in collaboration with Merck & Co., Inc., Kenilworth, NJ, USA (known as "MSD" outside the United States and Canada). The study is evaluating the combination of efti with MSD’s KEYTRUDA (pembrolizumab) in up to 183 patients with second line head and neck squamous cell carcinoma or non-small cell lung cancer in first and second line.

The trial is a Phase II, Simon’s two-stage, non-comparative, open-label, single-arm, multicentre clinical study that is taking place in study centres across Australia, Europe, the UK and US.

Patients participate in one of the following:
• Part A – First line Non-Small Cell Lung Cancer (NSCLC), PD-X naive
• Part B – Second line NSCLC, PD-X refractory
• Part C – Second line Head and Neck Squamous Cell Carcinoma (HNSCC), PD-X naive

TACTI-002 is an all-comer study in terms of PD-L1 status, a well-known predictive marker for response to pembrolizumab monotherapy especially in NSCLC and HNSCC. PD-L1 expression is typically reported in three groups for NSCLC: < 1%, 1-49% and ≥ 50% (Tumour Proportion Score or TPS) and in HNSCC: < 1, 1-19 and ≥ 20 (Combined Positive Score or CPS). Patients with a high PD-L1 status are typically more responsive to anti-PD-1 therapy such as pembrolizumab, whereas those with low PD-L1 status are overall significantly less responsive.

On June 04, 2021 Auransa, Inc., an artificial intelligence (AI) company developing precision medicines in areas of unmet medical needs, and Polaris Quantum Biotech (POLARISqb), a quantum drug design company, reported a research collaboration addressing therapeutics for neglected diseases disproportionately affecting women (Press release, Auransa, JUN 4, 2021, View Source [SID1234635628]).

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The partnership seeks to discover treatments that may tackle many such diseases, and their complementary expertise promises to seek solutions that elude medical research. Auransa is an AI-driven biotech company, with a pipeline of novel compounds for various diseases. Auransa’s proprietary predictive computational platform, SMarTR Engine, uses computational approaches to tackle disease heterogeneity to predict targets and compounds, generating insights from molecular data. POLARISqb built the first drug discovery platform using quantum computing, making the process ten times faster. POLARISqb’s TachyonTM platform scans billions of molecules from a massive chemical space, finding novel molecular drugs.

"We are excited about collaborating with Polaris to undertake a neglected area in the pharmaceutical industry. As women CEOs, we’ve joined forces to tackle female diseases like endometriosis, polycystic ovary syndrome, triple negative breast cancer or ovarian cancer. Together, I believe that we will be able to combine our expertise in biology and chemistry to generate quality solutions for hard to tackle or neglected diseases affecting women’s health." stated Pek Lum, Ph.D., CEO of Auransa.

"Quantum Computing technology is coming of age, allowing us to shorten the time to discover new drugs and scale up to multiple targets. We are thrilled to be able to combine our technology with Auransa’s and tackle neglected diseases affecting women. Together, we have unique perspectives on the industry and of unmet needs the pharmaceutical industry can and should tackle, utilizing the best technology available." said Dr. Shahar Keinan, POLARISqb CEO.

On June 4, 2021 TG Therapeutics, Inc. (NASDAQ: TGTX), reported data from TG-1701, the Company’s investigational once-daily, oral BTK inhibitor, as a monotherapy and as a triple therapy in combination with ublituximab, the Company’s novel glycoengineered anti-CD20 monoclonal antibody, and UKONIQ (umbralisib), the Company’s once-daily, inhibitor of PI3K-delta and CK1-epsilon in patients with front line or relapsed/refractory non-Hodgkin’s lymphoma (NHL) and chronic lymphocytic leukemia (CLL) (Press release, TG Therapeutics, JUN 4, 2021, View Source [SID1234583532]). Data from this trial were made available on demand this morning during the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting. Presentation highlights are included below.

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Michael S. Weiss, the Company’s Executive Chairman and Chief Executive Officer, stated, "We are pleased to see that with additional patients and longer follow-up, TG-1701, our BTK inhibitor, continues to show encouraging clinical activity paired with what appears to be a tolerable safety profile, especially in the triple combination with U2. It is also exciting to see some early complete responses in patients treated with the triple therapy. We look forward to continuing to enroll on this trial and presenting additional data."

PRESENTATION HIGHLIGHTS:

Poster Presentation Title: TG-1701, A Selective Bruton Tyrosine Kinase (BTK) Inhibitor, as Monotherapy and in Combination with Ublituximab and Umbralisib (U2) in Chronic Lymphocytic Leukemia (CLL) and Lymphoma

A total of 125 patients with R/R CLL or B-cell lymphoma have been treated with TG-1701, with patients receiving monotherapy in the dose-escalation cohort (n=25), 200 mg in a dose-expansion cohort (n=61), 300 mg in a CLL dose-expansion cohort (n=20), or TG-1701 in combination with U2 in the dose escalation cohort (n=19).
TG-1701 monotherapy was well tolerated and the maximum tolerated dose was not reached up to 400 mg QD.
Adverse Events (AEs) of special interest in patients treated with 200 mg and 300 mg QD of TG-1701 (n=81), included Grade 3 hypertension (4.9%), atrial fibrillation (1.2%), and no instances of major bleeding observed. Grade 3 AEs occurring in ≥10% of patients treated with U2+1701 included diarrhea (11%), neutropenia (11%), ALT increase (16%), and AST increase (16%), and Grade 4 AEs occurring in ≥10% of patients treated with U2+1701 included neutropenia (11%).
At a median follow up of 12.2 months in the 200 mg QD monotherapy expansion cohorts, overall response rates (ORR) were: 95% (19/20) in CLL, 65% (13/20) in mantle cell lymphoma (MCL), and 95% (19/20) in Waldenstrom macroglobulinemia (WM).
100% ORR observed at a median follow up of 8.6 months in the 300 mg CLL monotherapy cohort (n=19).
At a median follow up of 15.6 months, the 1701+U2 dose escalation (using doses of 100mg to 300 mg QD of TG-1701) resulted in 79% ORR, with 21% CR rate across patients with WM, CLL, marginal zone lymphoma (MZL), diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL) (n=19).
Data presented at ASCO (Free ASCO Whitepaper) 2021 is available on the Publications page of the Company’s website at View Source