Lutris Pharma Presents New Data from Its Completed Clinical Trial of LUT014 Gel Demonstrating Efficacy in Treating Acneiform Rash Associated with Use of Anti-EGFR Cancer Therapies at AACR Annual Meeting 2025

On April 28, 2025 Lutris Pharma, a clinical stage biopharmaceutical company focused on improving anti-cancer therapies by reducing cutaneous dose limiting toxicity, reported data from its recently completed double-blind, placebo-controlled phase 2 randomized clinical trial of lead therapy, LUT014 gel, demonstrating statistically-significant reductions in dose-limiting acneiform rash in patients treated with epidermal growth factor receptor (EGFR) inhibitor therapy (Press release, Lutris Pharma, APR 28, 2025, View Source [SID1234652272]). This new clinical data, showing that Lutris’ topically-applied novel B-Raf inhibitor gel is optimized for paradoxical MAPK activation, was presented yesterday in an oral presentation at the Clinical Trials Plenary Session at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2025.

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Presentation Details:

Presentation Title: A double-blind placebo-controlled randomized phase 2 clinical trial to assess the efficacy of a topical BRAF inhibitor for acneiform rash toxicities from anti-EGFR therapies
Presenting Author: Anisha B. Patel, MD, Associate Professor, Department of Dermatology, University of Texas MD Anderson Cancer Center, Houston, TX
Abstract Number: CT018
Session Title: New Frontiers in Precision Oncology
"Due to the widespread use of EGFR inhibitors for cancer treatment and the frequent occurrence of dermal toxicities, many patients do not receive optimal cancer therapy. This is often because the toxicity leads to dose reductions or complete discontinuation of treatment," stated Benjamin W. Corn, M.D., Chief Medical Officer of Lutris Pharma. "By reversing the inhibitory effect of anti-EGFR therapy on downstream signaling in skin cells, we firmly believe LUT014 has the potential to be a key therapeutic, offering significant benefits to patients with no other effective treatment options. In the trial, as we expected, LUT014 demonstrated statistically significant improvement in acneiform rash compared to placebo, with highly successful outcomes in both intention-to-treat and per-protocol patient analyses. LUT014 was also shown to be safe and well tolerated, with fewer adverse events reported than in the placebo group, with the majority of adverse events being mild."

"This was the first placebo-controlled randomized clinical trial demonstrating the benefit and safety of an agent for the treatment of the acneiform rash associated with anti-EGFR therapy. Therefore, having these overwhelmingly positive results for LUT014 selected for an oral presentation at the prestigious AACR (Free AACR Whitepaper) Annual Meeting, is a testament to the potential of our lead asset and a significant milestone for the company," added Noa Shelach, Ph.D., Chief Operating Officer of Lutris Pharma. "In addition, our successful $30 million financing, completed in January 2025, allows us to continue advancing our clinical development program as we pursue our goal of commercializing LUT014 which will align with our mission to enhance the effectiveness of anti-cancer therapies and significantly improve the quality of life for patients."

The trial enrolled 118 colorectal cancer patients from 23 clinical sites, all of whom had developed grade 2 or non-infected grade 3 acneiform rash while receiving cetuximab or panitumumab. Participants were randomized in a 1:1:1 ratio to receive either LUT014 gel 0.03%, LUT014 gel 0.1%, or a placebo gel. The gel was applied daily for 28 days.

The primary endpoint was the proportion of patients who achieved treatment success, measured by an improvement of at least one grade in Common Terminology Criteria for Adverse Events (CTCAE) scoring or an improvement of at least 5 points in the Functional Assessment of Cancer Therapy (FACT)-EGFRI-18 HRQoL skin-specific assessment. The study employed both an intention-to-treat (ITT) analysis and a Per-Protocol (PP) analysis (i.e., patients who dropped out or did not discontinue their EGFR inhibitor for reasons unrelated to the rash, such as disease progression were excluded from the analysis). Sample size calculation was based on an expected treatment success of 20% for the placebo group and 50% for one of the treatment groups. A total of 117 patients were required for a two group ꭕ2 test with a 0.05 two-sided significance and 80% power.

Efficacy is shown in the table below. In the ITT as well as the PP, the composite endpoint demonstrated statistically significant rates of success for the high dose LUT014 group, compared to placebo.

Treatment
Arm

N

Success
Rate

(ITT)

P
Value

N

Success
Rate

(PP)

P Value

LUT-014 0.1%

39

69 %

0.0015

25

76 %

0.002

LUT-014 0.03%

40

47.5 %

0.12

29

59 %

0.07

Placebo

39

33 %

29

34.5 %

About EGFR Inhibitor-Induced Rash
EGFR is a receptor on the surface of cells which is expressed in many normal epithelial tissues, including skin. The EGFR signaling pathway is one of the key pathways that regulate growth, survival, proliferation, and differentiation of cells. B-Raf is a protein encoded by the BRAF gene and is a downstream effector component of the EGFR signaling pathway. EGFR has been shown to be over-activated in various human cancers, including colorectal, lung, head and neck, urinary bladder, pancreatic and breast cancers, eliciting downstream phosphorylation and activation of the MAP Kinase pathway.

EGFR inhibitors can block the EGFR signal responsible for cell growth. Among the various types of pharmacological therapies for cancer, EGFR inhibitors are increasingly being used both as primary therapy as well as in patients who have progressed on prior chemotherapy treatments. Although effective as an anti-cancer therapy leading to tumor shrinkage, EGFR inhibitors have many adverse reactions associated with their use. The majority of patients treated with EGFR inhibitors will experience adverse dermatological side effects typically manifested as a papulopustular skin rash, also known as acneiform lesions, which can impact quality of life and affect adherence to therapy.

About LUT014
LUT014 is a novel B-Raf inhibitor which is applied topically to the skin. When the B-Raf protein is mutated, as is the case in some human cancers such as melanoma, blocking this pathway leads to apoptosis of the cells and tumor shrinkage. However, when the same pathway is blocked in normal, non-mutated cells, the opposite happens: the MAPK pathway is activated, and cells start growing. This phenomenon is recognized as the paradoxical effect of B-Raf Inhibitors. LUT014 harnesses the paradoxical effect of B-Raf Inhibitors in order to enhance cell proliferation and balance cell destruction, typical to radiation dermatitis.

Actinium Highlights Mutation Agnostic Antileukemic Activity of Actimab-A Against FLT3, NPM1, KMT2A and TP53 Mutations in AML Models Demonstrating Backbone Potential for Acute Myeloid Leukemia Treatment at the American Association for Cancer Research Annual Meeting

On April 28, 2025 Actinium Pharmaceuticals, Inc. (NYSE AMERICAN: ATNM) (Actinium or the Company), a pioneer in the development of targeted radiotherapies, reported data presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting supporting Actimab-A’s mutation agnostic antileukemic effect and backbone therapy potential in preclinical acute myeloid leukemia (AML) models (Press release, Actinium Pharmaceuticals, APR 28, 2025, View Source;302439223.html [SID1234652271]). The preclinical data demonstrate that the combination of Actimab-A with standard of care AML therapies including menin and FLT3 inhibitors and the hypomethylating agent (HMA) azacitidine resulted in significant antileukemic activity in AML cells lines with FLT3, NPM1, KMT2A and TP53 mutations. Additionally, in animal models, Actimab-A significantly enhanced tumor growth inhibition, prolonged the duration of response and survival when combined with the menin inhibitor revumenib (Syndax Pharmaceuticals, Inc.), and potentiated AML cell killing in combination with the FLT3 inhibitor gilteritinib (Astellas Pharma US, Inc.) and HMA azacitidine.

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Sandesh Seth, Actinium’s Chairman and CEO, said, "In multiple clinical trials, Actimab-A has demonstrated potent single agent activity, synergy with other therapeutic modalities and efficacy in patients with high-risk features such as a TP53 mutation. To our knowledge, Actimab-A is the only AML therapy to achieve all of these outcomes, which we attribute to its mutation agnostic, backbone therapy profile. The data presented at AACR (Free AACR Whitepaper) further support Actimab-A’s mutation agnostic mechanism of action across several of the most commonly expressed mutations and synergy with the targeted therapies approved for patients with these mutations. With multiple clinical trials underway and being planned across the AML treatment settings, we are focused on generating strong clinical outcomes starting in the second half of this year and committed to realizing Actimab-A’s potential for patients who have significant unmet needs."

Actimab-A is Actinium’s lead radiotherapy that delivers Actinium-225, a potent alpha-emitter radioisotope payload that can produce lethal double strand DNA breaks to kill targeted cells that express CD33. CD33 is expressed ubiquitously in AML and in other myeloid malignancies such as myeloid dysplastic syndromes (MDS), which Actinium estimates to be an addressable market of over 100,000 patients in the U.S. and EU5. Actimab-A is also being advanced into a pivotal Phase 2/3 trial in combination with the chemotherapy regimen CLAG-M in patients with relapsed or refractory AML and in newly diagnosed AML in combination with Venetoclax and ASTX-727 (Taiho Oncology, an Otsuka holdings company) an oral hypomethylating agent (HMA) under a cooperative research and development agreement (CRADA) with the National Cancer Institute (NCI). Actimab-A has demonstrated a mutation agnostic profile with positive clinical results in high-risk relapsed and refractory (r/r) AML patients including those with a TP53 gene mutation, prior Venetoclax treatment and prior bone marrow transplant (BMT).

The Actimab-A AACR (Free AACR Whitepaper) presentation is available for viewing on the Presentations& Webinars page of Actinium’s website HERE.

Title: Actimab-A (Lintuzumab-Ac-225) has potent mutation agnostic antileukemic activity in preclinical models of AML
Abstract Number: 594

GlycoNex Presents Preclinical Data on GNX1021 at AACR Annual Meeting 2025

On April 28, 2025 GlycoNex, Inc. (4168, hereinafter referred to as GNX), a clinical stage biotechnology company focused on the development of glycan-directed cancer immunotherapies, reported the presentation of preclinical data on GNX1021, its lead antibody-drug conjugate (ADC) program, at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2025 (Press release, GlycoNex, APR 28, 2025, View Source [SID1234652270]). The presentation is part of a poster session held on April 28, 2025, at McCormick Place in Chicago.

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GNX1021 is a novel ADC that targets branched Lewis B/Y (bLeB/Y), a tumor-associated glycan highly expressed in gastric cancer and other solid tumors. The target has a distinct expression profile compared to HER2 and CLDN18—two well-known markers in gastric cancer—allowing GNX1021 to potentially treat patients who are not eligible for current HER2- or CLDN18-targeted therapies.

The poster presents preclinical data showing GNX1021’s antitumor activity in gastric cancer models with high bLeB/Y expression, along with a favorable safety profile in nonclinical studies. Findings suggest that GNX1021 may offer a differentiated therapeutic option for gastric cancer patients with limited targeted treatment choices.

"These data demonstrate the potential of GNX1021 to expand the treatment landscape for gastric cancer by targeting a glycan biomarker not addressed by existing therapies," said Dr. Mei-Chun Yang, CEO of GlycoNex. "As a first-in-class anti-glycan ADC, GNX1021 exemplifies our approach to developing next-generation oncology therapeutics designed to overcome tumor heterogeneity and drug resistance."

GlycoNex is advancing GNX1021 through IND-enabling preclinical development, with an IND submission planned for Q1 2026 and Phase 1 trial initiation expected in Q2 2026.

Presentation Details:

Event:

American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2025

Session Category:

Experimental and Molecular Therapeutics

Session:

Growth Factor Receptors and Other Surface Antigens as Targets for Therapy 1

Abstract Title: (#2932)

GNX1021, a novel ADC targeting glycans with branched Lewis B/Y, demonstrated preclinical tumor control activity in gastric cancer models and favorable safety

Date and Time:

April 28, 2025; 2:00 pm CDT

Location:

McCormick Place Convention Center, Chicago

Poster Section 17, Poster Board 6

AVEO Oncology, an LG Chem company, Announces Three Poster Presentations at ASCO 2025 Annual Meeting

On April 28, 2025 AVEO Oncology, an LG Chem company ("AVEO"), a biopharmaceutical company committed to providing differentiated solutions to improve cancer patients lives, reported that three abstracts were accepted for presentation at the upcoming American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2025 annual meeting this May 30-June 3, 2025, in Chicago, IL (Press release, AVEO, APR 28, 2025, View Source [SID1234652269]).

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Presentation Details

Title: Efficacy of second line (2L) treatment with tivozanib (Tivo) as monotherapy or with nivolumab (Nivo) in patients (pts) with metastatic renal cell carcinoma (mRCC) previously treated with an immune checkpoint inhibitor (ICI) combination of ipilimumab (Ipi)/Nivo or vascular endothelial growth factor receptor-tyrosine kinase inhibitor (VEGFR-TKI)/ICI in the Phase 3 TiNivo-2 study
First Author: Alexander Chehrazi-Raffle, MD, City of Hope Cancer Center
Abstract Number: 4540
Poster Session: Genitourinary Cancer—Kidney and Bladder
Poster Board: 340
Date and Time: Monday, June 2, 2025, 9:00am – 12:00 PM CDT

Title: FIERCE-HN: A multicenter, randomized, double-blind, placebo-controlled, phase 3 study of ficlatuzumab (HGF/cMET Mab) in combination with cetuximab in participants with recurrent or metastatic (R/M) HPV negative head and neck squamous cell carcinoma (HNSCC)
First Author: Julie E. Bauman, MD, MPH, George Washington University Cancer Center
Abstract Number: TPS6115
Poster Session: Head and Neck Cancer
Poster Board: 520a
Date and Time: Monday, June 2, 2025, 9:00 AM – 12:00 PM CDT

Title: A phase1b dose escalation study of AV-380 (anti-GDF15 monoclonal antibody) in combination with standard-of-care therapy in cancer patients with cachexia
First Author: Eric Roeland, MD, FAAHPM, Oregon Health & Science University
Abstract Number: TPS12142
Poster Session: Symptom Science and Palliative Care
Poster Board: 159a
Date and Time: Monday, June 2, 2025, 1:30-4:30 PM CDT

Boehringer’s new zongertinib data demonstrates durable and clinically meaningful results in patients with HER2 (ERBB2)-mutant advanced NSCLC

On April 28, 2025 Boehringer Ingelheim reported new and updated data from the Beamion LUNG-1 trial evaluating zongertinib in previously treated patients with HER2 (ERBB2)-mutant advanced non-small cell lung cancer (NSCLC) (Press release, Boehringer Ingelheim, APR 28, 2025, View Source [SID1234652268]). The data was featured in the official press program at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2025 and simultaneously published in The New England Journal of Medicine.

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"These data presented at AACR (Free AACR Whitepaper) 2025 suggest that zongertinib may offer a new approach to treating patients with non-small cell lung cancer with activating HER2 mutations," said the trial’s coordinating investigator, Dr. John Heymach, MD, PhD, chair of Thoracic/Head and Neck Medical Oncology at The University of Texas MD Anderson Cancer Center. "Notably, more than 70% of patients experienced a tumor response, which is highly meaningful for those with this subtype of lung cancer. If approved by the FDA, zongertinib would be the first oral, targeted treatment option that addresses an unmet need for these patients."

Data from the most recent analysis showed durable response and clinically meaningful results with zongertinib in previously treated patients with advanced NSCLC who have HER2 mutations within the tyrosine kinase domain (TKD) (N=75). The ORR was 71% (95% CI: 60-80), with 7% complete response, 64% partial response, and 96% disease control in previously treated patients. Additionally, zongertinib had intracranial activity in previously treated patients (n=27, who were evaluable) with brain metastases, with 41% achieving response and 81% disease control. At AACR (Free AACR Whitepaper) 2025, the median DoR of 14.1 and median PFS of 12.4 months were presented for the first time.

Itziar Canamasas, Global Head of Oncology at Boehringer Ingelheim, said: "Zongertinib has the potential to reset the benchmark for patients with HER2-mutant advanced non-small cell lung cancer, a patient population that has historically faced a poor prognosis. At Boehringer, we take cancer care personally; these updated data reaffirm our approach of addressing areas with high unmet need and letting our research guide us to where we can have the biggest impact for patients."

Additional analyses of previously treated patients with HER2 mutations demonstrated zongertinib’s clinically meaningful results

Initial results in patients with advanced NSCLC with HER2 mutations in the TKD, who were previously treated with both platinum-based chemotherapy and subsequent HER2-directed antibody drug conjugates (ADC) (N=31), demonstrated an ORR of 48% (95% CI: 32-65) with 97% (95% CI: 15-52) of patients achieving disease control. An exploratory cohort (n=20) that included previously treated patients with advanced NSCLC with HER2 mutations outside of the TKD demonstrated an investigator-assessed ORR of 30% (95% CI: 15-52) and a DCR of 65% (95% CI: 43-82). This is the largest known dataset of patients with previously treated advanced NSCLC who have HER2 mutations outside the TKD. Both of these data sets were presented at AACR (Free AACR Whitepaper) 2025 and are included in The New England Journal of Medicine publication.

The data presented at AACR (Free AACR Whitepaper) 2025 demonstrated a manageable safety profile for zongertinib with no drug-related deaths, cases of interstitial lung disease (ILD) or cardiotoxicity reported. The most commonly reported adverse event (AE) was grade 1 diarrhea, with low incidence of grade ≥3 drug-related events (17%) in patients with TKD mutations (N=75).

AACR 2025 presentation: summary of key efficacy endpoints

Endpoint

Patients with TKD mutations (N = 75)

Patients with TKD mutations and
prior HER2-directed ADC treatment (N = 31)

Patients with non-TKD mutations (n = 20)

ORR, %

95% CI

71*

60-80

48*

32–65

30**

15-52

CR, %

7*

3*

0**

PR, %

64*

45*

30**

DCR, %

95% CI

96*

89-99

97*

84-99

65**

43-82

Median DoR

95% CI

14.1 months***

6.9–NE

n/a

n/a

Median PFS

95% CI

12.4 months***

8.2–NE

n/a

n/a

*Confirmed response by BICR according to RECIST v1.1
**Confirmed response by investigator review according to RECIST v1.1
*** Median DoR and median PFS are based on Kaplan Meier estimates

About non-small cell lung cancer (NSCLC)
Lung cancer claims more lives than any other cancer type1 and the incidence is set to increase to over 3 million cases worldwide by 2040.2 NSCLC is the most common type of lung cancer.3 The condition is often diagnosed at a late stage,4 and fewer than 3 in 10 patients are alive five years after diagnosis.5 People living with advanced NSCLC can experience a detrimental physical, psychological, and emotional impact on their daily lives. There remains a high unmet need for additional treatment options for people living with advanced NSCLC. Up to 4% of lung cancers are driven by HER2 mutations (or gene alterations).6 Mutations in HER2 can lead to overexpression and overactivation, which can in turn result in uncontrolled cell production, inhibition of cell death and promotion of tumor growth and spread.7

About zongertinib
Zongertinib is an investigational irreversible tyrosine kinase inhibitor (TKI) that selectively inhibits HER2 while sparing wild-type EGFR, thereby limiting associated toxicities. This orally administered, targeted therapy was granted FDA Fast Track Designation in 2023, followed by Breakthrough Therapy Designation in the U.S. and China for the treatment of adult patients with unresectable or metastatic NSCLC whose tumors have activating HER2 mutations and who have received prior systemic therapy. An application for accelerated approval was granted Priority Review status by the FDA in February 2025. In addition, Japan’s Pharmaceuticals and Medical Devices Agency granted Orphan Drug Designation to zongertinib.

A recent study has shown pre-clinically that the investigational compound zongertinib has potential for further clinical study in HER2 dependent solid cancers as monotherapy and as concurrent treatment with ADC therapy. In addition, zongertinib is being evaluated in Beamion LUNG-2 (NCT06151574)4, a global Phase III trial, compared to standard of care as first-line treatment in patients with unresectable, locally advanced or metastatic NSCLC who have activating HER2 TKD mutations.

About the Beamion clinical trial program
Beamion LUNG-1 (NCT04886804): An open-label, Phase I dose escalation trial, with dose confirmation and expansion, of zongertinib as monotherapy in people with advanced or metastatic solid tumors and NSCLC with activating HER2 alterations. The study has 2 parts. The first part is open to adults with different types of advanced cancer (solid tumors with changes in the HER2 gene) for whom previous treatment was not successful. The second part is open to people with advanced non-small cell lung cancer with a specific mutation in the HER2 gene. Beamion LUNG-2 is a phase 3, open label, randomized, active-controlled study in patients with unresectable, locally advanced or metastatic non-squamous NSCLC harboring HER2 TKD mutations to evaluate zongertinib compared with standard of care.