On January 17, 2024 Amplia Therapeutics reported that the first patient in the Phase IIa portion of the ACCENT trial has begun dosing (Press release, Amplia Therapeutics, JAN 17, 2024, View Source [SID1234639272]). The ACCENT trial is examining the combination of Amplia’s best-in-class FAK inhibitor narmafotinib in combination with standard-of-care chemotherapy in first-line patients with advanced pancreatic cancer.

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In November 2023, the Company announced completion of the Phase 1b stage of the ACCENT trial where ascending doses of narmafotinib, in combination with the standard-of-care chemotherapy regime of gemcitabine and Abraxane, were dosed to first-line patients with advanced pancreatic cancer. This dose-escalation stage identified a safe and well-tolerated dose of narmafotinib that provides sufficient circulating drug levels to significantly block the activity of the FAK enzyme.

Importantly, there were promising preliminary signs of efficacy from the collected Phase 1b data. The identified dose of narmafotinib is now being tested in patients, in combination with gemcitabine and Abraxane, in a Phase 2a trial.

The Phase 2a trial is being conducted at six trial sites open in Melbourne, Sydney and Brisbane and the five additional sites which have been opened in Korea. The trial will initially enrol 26 patients over the coming months and an interim analysis of efficacy will then be conducted in mid-2024. An efficacy assessmentshowing six or more partial or complete responses out of the 26 patients will be considered statistically significant to continue the trial. An additional 24 patients will then be enrolled to give a total of 50 patients for this trial.

Amplia CEO and MD Dr Chris Burns commented: "Initiation of the Phase 2a stage of the trial is a significant milestone for Amplia. We are excited to be moving ahead with the nextstage of the ACCENT trial with a safe and well-tolerated dose of narmafotinib. The trial in advanced pancreatic patients will determine whether narmafotinib, in combination with gemcitabine and Abraxane, provides improved efficacy forthe treatment of this devastating cancer. Patients and clinicians are desperate for improved treatment options given the current five-year survival for newly diagnosed patients is only 12%."

About the ACCENT Trial
The protocol for the ACCENT trial is entitled ‘A Phase 1b/2a, Multicentre, Open Label Study of the Pharmacokinetics, Safety and Efficacy of AMP945 in Combination with Nab-paclitaxel and Gemcitabine in Pancreatic Cancer Patients’. The trial is a single-arm open label study conducted in two stages. The first stage (Phase 1b) determined an optimal dose of AMP945 by assessing the safety, tolerability, pharmacokinetics, pharmacodynamics and preliminary efficacy of AMP945 when dosed in combination with gemcitabine and Abraxane in first-line patients with advanced pancreatic cancer.

This second stage (Phase 2a), of the trial is designed to assess efficacy in combination with gemcitabine and Abraxane. The primary endpoints are Objective Response Rate (ORR) and Duration on Trial (DOT) with secondary endpoints being Progression Free Survival (PFS) and Overall Survival (OS). Safety and tolerability will continue to be assessed.

More information about the ACCENT trial, including a list of participating sites, can be found via the Amplia Therapeutics website and at ClinicalTrials.gov under the identifier NCT05355298. The Company will provide further updates on the trial as recruitment proceeds.

This ASX announcement was approved and authorised for release by the Board of Amplia Therapeutics.

On January 17, 2024 Imugene Limited (ASX: IMU), a clinical stage immuno-oncology company, reported a clinical trial update of its Phase 1 MAST (Metastatic Advanced Solid Tumours) trial evaluating the safety and efficacy of novel cancer-killing virus CF33-hNIS (VAXINIA) (Press release, Imugene, JAN 17, 2024, https://mcusercontent.com/e38c43331936a9627acb6427c/files/239ef0da-fe2d-1182-07cf-4453d3a72429/Phase_1_CF33_hNIS_Study_Update_Positive_Early_Signals.pdf [SID1234639271]).

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As of 12 January 2024, 38 patients have been dosed with VAXINIA during the continuing dose escalation phase, comprised of 19 patients dosed intratumourally and 19 patients dosed intravenously as either monotherapy or in combination with pembrolizumab.
31 patients were evaluable for efficacy (received at least their first scan at day 42). In the IT cohorts (14 patients), 7 of 15 (47%) injected lesions had a reduction in tumour burden, 3 lesions were completely eradicated. 3 patients (21%) had an objective response: 1 complete response by iRECIST in a patient with cholangiocarcinoma (a type of biliary tract cancer); and 2 partial responses in patients with melanoma (skin cancer) by RECIST. In IV cohorts (17 patients), 53% of patients achieved stable disease as their best response. • Patients who received prior checkpoint blockade therapy derived clinical benefit with and without pembrolizumab.
Trial expansion is planned for 10-20 patients with biliary tract cancers.
Early results presented this week at the annual ASCO (Free ASCO Whitepaper)-GI Symposium in San Francisco, California, show that 7 patients with gastrointestinal cancers who received CF33-hNIS alone including 3 colorectal, 2 biliary tract, 1 pancreatic and 1 liver cancer showed positive treatment effects, with a disease control rate (all CR, PR and SD) of 86%. Importantly, in these patients, changes in tumour burden correlated with systemic immunological changes known to promote anti-tumour immunity. The poster "Oncolytic Virus CF33-hNIS Monotherapy for the Treatment of Gastrointestinal Malignancies" will be presented on 18 January 2024 during Session A: Cancers of the Esophagus and Stomach and Other GI Cancers from 11:45 AM-1:15 PM.
Imugene MD & CEO Leslie Chong said: "This latest data reinforces the early positive responses we’ve seen in gastrointestinal cancers and in particular for cholangiocarcinoma (bile duct cancer). It provides an excellent platform to investigate the impact of VAXINIA at higher dose levels as we also expand the trial to additional patients with hard-to-treat biliary tract cancers. It is a proud moment for us to be able to present these results at ASCO (Free ASCO Whitepaper)-GI, and promote the potential of VAXINIA and CF33 more broadly."

Notably, 1 patient with biliary tract cancer, treated IT with mid-dose level displayed pseudoprogression (see below) with a 49% increase in tumour burden after 2 cycles of therapy. However, by the 4th cycle they achieved a Complete Response (iCR) with no known recurrence in over 430 days. A second patient with bile duct cancer, who previously progressed on prior drug therapies, achieved Stable Disease (SD) for > 4 months upon receiving IV-administered CF33-hNIS.

About Biliary Tract Cancers
Bile duct cancers are difficult to treat and typically respond modestly to immunotherapy drugs. Pseudoprogression is a phenomenon in which the cancer initially appears to be growing, largely due to the cancer cells being infected by the virus then followed by infiltration of cancer fighting immune cells. However, it is usually followed by a decrease in tumour burden when the therapy takes effect. This phenomenon can benefit patients receiving immunotherapy but often leads to premature discontinuation of treatment owing to the false impression the cancer is growing.

About the MAST Trial
The multicenter Phase 1 MAST trial commenced by delivering a low dose of VAXINIA to patients with metastatic or advanced solid tumours who have had at least two prior lines of standard of care treatment. The City of Hope-developed oncolytic virus has been shown to shrink colon, lung, breast, ovarian and pancreatic cancer tumours in preclinical laboratory and animal models. Overall, the study aims to recruit cancer patients across approximately 10 trial sites in the United States and Australia.

The clinical trial is titled "A Phase I, Dose Escalation Safety and Tolerability Study of VAXINIA (CF33- hNIS), Administered Intratumourally or Intravenously as a Monotherapy or in Combination with Pembrolizumab in Adult Patients with Metastatic or Advanced Solid Tumours (MAST)." The trial commenced in May 2022 and is anticipated to run for approximately 24 months while being funded from existing budgets and resources.

Full study details can also be found on clinicaltrials.gov under study ID: NCT05346484.

On January 16, 2024 Cellectar Biosciences, Inc. (NASDAQ: CLRB), a late-stage clinical biopharmaceutical company focused on the discovery, development and commercialization of drugs for the treatment of cancer, reported promising preclinical data for its proprietary novel alpha-emitting phospholipid radiotherapeutic conjugate, CLR 121225 (225Ac-CLR 121225) an actinium-labeled phospholipid ether (PLE), in pancreatic cancer models (Press release, Cellectar Biosciences, JAN 16, 2024, View Source [SID1234643477]). The development of this compound will expand the company’s clinical pipeline of PLE cancer targeting compounds to include targeted alpha therapies (TATs), complementing its beta-emitting phospholipid radiotherapeutic conjugate, iopofosine I 131, which achieved its primary endpoint in the CLOVER WaM pivotal study in highly refractory Waldenstrom’s macroglobulinemia patients.

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Cellectar’s PLE platform may provide unique advantages which overcome the issues experienced by existing TAT delivery platforms. While current TAT platforms, such as antibodies and peptides, possess the potential to be effective for treating cancers with low tumor volume, they are challenged to treat higher volume or bulky tumors due to insufficient penetration and the need for high quantities of the target epitope. Cellectar’s PLE’s possess biochemical properties that enable penetration of the TAT payload deep into the tumor mass and the abundance of lipid rafts on tumor cells provides near universal delivery and enhanced outcomes.

"The advancement of our TAT program is part of our overall strategy to develop a comprehensive portfolio of first- and best-in-class radiotherapeutics designed to treat both blood cancers and solid tumors that now includes both alpha and beta-emitting radiotherapeutics," commented James Caruso, president and CEO of Cellectar. "Our promising preclinical data with actinium-225 highlights the potential utility of our PLE platform to provide targeted delivery to nearly any isotope resulting in compounds with excellent activity and tolerability. Our novel TAT compounds, including actinium-225, lead-212 and others, have demonstrated this potential in pancreatic cancer, triple-negative breast cancer and other types of tumor models which allows us to deliver the optimal radioisotope based on tumor biology to maximize outcomes. These data provide further evidence supporting the continued development of CLR 121225, which is expected to enter a Phase 1 first-in-human study later this year or early next year."

In preclinical studies, CLR 121225 demonstrated potent anti-tumor activity in refractory pancreatic cancer mouse xenograft models. A single administration at each dose level (100nCi, 250nCi and 500nCi) resulted in tumor volume reduction in a dose dependent manner with the highest dose providing near complete eradication of the tumor. Additionally, it was shown that CLR 121225 demonstrated excellent biodistribution; approximately 15 – 20% of the infused drug accumulated in the tumor within four hours and continued to accumulate over 72 – 96 hours. The mice had no end organ toxicities demonstrating good tolerability. The data are consistent with experiments using other alpha emitters conjugated to the company’s proprietary PLE targeted delivery platform.

On January 16, 2024 Adagene Inc. ("Adagene") (Nasdaq: ADAG), a company transforming the discovery and development of novel antibody-based therapies, reported data from its presentation at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2024 Gastrointestinal (GI) Cancers Symposium, taking place January 18-20 in San Francisco (Press release, Adagene, JAN 16, 2024, View Source [SID1234639974]).

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"The expanded therapeutic index for the masked ADG126 allows us to dose with a higher and more frequent effective dose of anti-CTLA-4 therapy than today’s options," said Daneng Li, MD and Associate Professor Department of Medical Oncology & Therapeutics Research at the City of Hope Comprehensive Cancer Center. "These promising data support further evaluation of this potential best-in-class anti-CTLA-4 antibody, ADG126, in combination with pembrolizumab for MSS CRC patients, including battling new liver lesions in those patients initially without detectable liver metastasis. We also see a tremendous opportunity to help patients in other tumor types where there is a significant need for safe and potent anti-CTLA-4 therapy."

Key highlights from the poster (November 30, 2023 data cutoff) include:

Results from dose escalation and dose expansion cohorts of ADG126 in combination with Merck & Co., Inc., Rahway, NJ, USA’s anti-PD-1 therapy KEYTRUDA (pembrolizumab) (200 mg/Q3W) demonstrated a best-in-class safety profile for ADG126 at doses from 6 mg/kg to 10 mg/kg in heavily pre-treated advanced/metastatic patients (N=46):
Limited dose-dependent toxicities were observed.
Grade 3 TRAEs occurred in 5/46 patients (10.8%), with no Grade 4 or 5 TRAEs and a discontinuation rate of 6.5% (3/46).
In dose escalation across tumor types, two partial confirmed responses (PRs) were observed among the three patients treated with ADG126 10 mg/kg Q3W, which triggered expansion cohorts at this dosing regimen. One of the patients had PD-1 refractory cervical cancer and the other had endometrial cancer. Both confirmed PRs are sustained after more than 55 weeks (over 14 cycles) of treatment.
In dose expansion of patients with MSS CRC, 12 evaluable patients without liver metastases were treated at the active, potent dose of 10 mg/kg Q3W:
Two confirmed PRs were observed in nine of these patients without peritoneal and liver metastases, resulting in an overall response rate of 22% in this subset.
An additional seven of these nine patients experienced stable disease (SD) for an overall disease control rate 100% (2 PRs and 7 SD).
Observation of these clinical activities triggered further expansion into Stage 2 of the Simon’s 2-stage design for this dose level, which is currently ongoing with data anticipated throughout 2024.
In a preliminary PFS analysis of those MSS CRC patients free of liver and peritoneal metastasis, a median PFS of seven months was observed in those treated with ADG126 10 mg/kg at two dosing frequencies pooled together [every three weeks (n=9) and every six weeks (n=6)]. The durable clinical activity of ADG126 in combination with pembrolizumab will continue to be evaluated as a larger cohort of subjects becomes evaluable at the 10 mg/kg Q3W dose level.
Commenting on the results, Heinz Josef-Lenz, MD, FACP, Associate Director for Clinical Research and Co-leader of the Translational Science Program at the USC Norris Comprehensive Cancer Center (NCCC) said, "I believe that CTLA-4 is an essential part of an effective immunotherapy for MSS CRC, yet physicians have been limited by the safety challenges from first generation options. The clinical profile of ADG126 in combination with pembrolizumab presents a great opportunity for MSS CRC patients that otherwise have limited immunotherapy options available."

ASCO-GI Poster Presentation Details

Title: Results of a phase 1b/2 study of ADG126 (a masked anti-CTLA-4 SAFEbody) in combo with pembrolizumab (Pembro) in patients (Pts) with metastatic microsatellite-stable (MSS) colorectal cancer (CRC)

Date: Saturday, January 20
Time: 6:30 a.m. – 7:55 a.m. Pacific Time
Onsite Location: Moscone West
Abstract Number: 127
Poster Board: H12
Consistent with the ASCO (Free ASCO Whitepaper)-GI embargo policy, the data are being released today in conjunction with the abstract publication.

KEYTRUDA is a registered trademark of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

On January 16, 2024 Celyad Oncology (Euronext: CYAD) (the "Company"), reported a fourth quarter 2023 business update and an outlook for 2024 (Press release, Celyad, JAN 16, 2024, View Source [SID1234639286]).

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Michel Lussier, interim Chief Executive Officer of Celyad Oncology, commented: "2023 has been a very important year for Celyad Oncology, after the changes that occurred in 2022. Our research team has made a remarkable progress to broaden the range of cancer indications that could be targeted by chimeric antigen receptor (CAR) T-cells and to tackle the main limitations of current CAR T-cell therapies. We have shared new data at several scientific and business conferences along the year, and published in high impact peer-reviewed journals. We are eager to see the impact of our efforts to unleash the power of our IP estate and stay at the forefront of next-generation CAR T-cell development."

2023 corporate accomplishments

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On August 24, 2023, the Company announced that it obtained commitments from Fortress, Tolefi and other longstanding existing shareholders to subscribe to a capital increase of up to €9.8 million in 2 tranches:

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A first tranche of 2.0 million was disbursed in the context of authorized capital as of September 4, 2023; and

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A second tranche subscribed by Fortress was approved by the extraordinary shareholders’ meeting of November 14, 2023. Following this private placement, the Company believes that its existing cash and cash equivalents should be sufficient, based on the current scope of activities, to fund operating expenses and capital expenditure requirements into the second quarter of 2025.

2023 operational highlights

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Multiplex short hairpin ribonucleic acid (shRNA) non-gene edited technology – All along 2023, we have collected and presented data validating our shRNA multiplexing approach:

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We developed a chimeric micro-RNA (miRNA) cluster to enable multiplexing of shRNAs, designed for easy, efficient, and tunable downregulation of up to four target genes simultaneously in CAR T-cells;

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Results detailing the technical aspects of the development of this platform have been published in Molecular Therapy – Nucleic Acids (Mol Ther Nucleic Acids. 2023, 34:102038). This publication has raised much interest from the community and was subjected to an editorial comment in the same volume of the Journal (Mol Ther Nucleic Acids. 2023, 34:102077);

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Additional data which demonstrate feasibility of this approach in the context of allogeneic cell therapies or with the aim to create therapies able to overcome the coinhibitory effects of exhaustion markers were presented at several scientific conferences. Posters are available on the company’s website, at View Source

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Multispecific NKG2D-based CAR T-cell platform – In 2023, we have compiled and presented data validating our multispecific approach targeting NKG2D ligands (NKG2DL):

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We have developed different CD19/NKG2DL, BCMA/NKG2DL and PSMA/NKG2DL multispecific CAR T-cells, utilizing both tandem constructs – that encompass the extracellular domain of the natural NKG2D receptor fused to a scFv targeting CD19, BCMA or PSMA, or dual constructs – that co-express the NKG2D-based CAR with an anti-CD19, anti-BCMA or anti-PSMA CAR, respectively;

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Our data provides the proof-of-concept that NKG2DL are valuable targets in a multispecific CAR approach and demonstrate our CD19/NKG2DL multispecific CAR T-cells are highly effective to counteract relapses due to CD19 antigen loss in vivo. In vitro data generated with BCMA/NKG2DL and PSMA/NKG2DL multispecific CAR T-cells further validate this approach in other hematological and solid indications. Posters are available on the company’s website, at View Source.

Financial highlights

As of December 31, 2023, the Company had cash and cash equivalents of €3.0 million and short-term investments of €4.0 million. The Company projects that its existing cash, cash equivalents and short-term investments should be sufficient to fund operating expenses and capital expenditure requirements into the second quarter of 2025. Therefore, the Company continues to project that its existing cash and cash equivalents will be sufficient to fund its estimated operating and capital expenditures over at least the next 12 months from the date of this press release.

Outlook for 2024

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More data and evidence in the context of the multispecific CAR T-cell platform and shRNA multiplexing approach will be shared in the first half of 2024, with the aim to develop assets ready for a potential initiation of clinical trials either by the Company and/or through strategic partnerships afterwards.

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Celyad Oncology will attend the 7th CAR-TCR Europe summit in London, UK (February 27-29, 2024), the must-attend forum to brainstorm and stay at the forefront of cell therapy innovations.

Financial Calendar 2024

•  April 5th, 2024

•  Full Year 2023 Financial Results

•  May 6th, 2024

•  Annual shareholders meeting

•  August 6th, 2024

•  First Half 2024 Interim Results

The financial calendar is communicated on an indicative basis and may be subject to change.