On June 24, 2025 TuHURA Biosciences, Inc. (NASDAQ:HURA) ("TuHURA" or the "Company"), a Phase 3 immune-oncology company developing novel technologies to overcome resistance to cancer immunotherapy, reported the initiation of its Phase 3 accelerated approval trial of IFx-2.0, TuHURA’s lead innate immune agonist, in patients with advanced or metastatic Merkel cell carcinoma (MCC) (Press release, TuHURA Biosciences, JUN 24, 2025, View Source [SID1234654093]).

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!

IFx-2.0 is designed to overcome primary resistance to checkpoint inhibitors (CPIs), such as Keytruda (pembrolizumab), and has demonstrated systemic anti-tumor specific immune responses (an abscopal effect) when administered intratumorally into cutaneous, subcutaneous, or accessible nodal lesions in the Company’s Phase 1b trial of IFx-2.0 in patients with advanced or metastatic MCC. In the Phase 1b trial, patients with advanced or metastatic MCC who progressed on either pembrolizumab or avelumab (anti-PD(L)-1) therapy, received weekly administration of IFx-2.0 for up to three doses followed by rechallenge with anti-PD(L)-1 therapy. Results demonstrated an overall response rate of 63% (2 CR, 5 PR) with two responses lasting 23 and 33 months and five ongoing responses (6, 11, 13, 19 and 23 months) as of the last follow-up.

"The initiation of IFx-2.0’s Phase 3 accelerated approval trial is a significant milestone for TuHURA and for the 40% to 50% of patients with advanced or metastatic MCC who may not respond to first line treatment with Keytruda (pembrolizumab)," stated James Bianco, M.D., President and Chief Executive Officer of TuHURA Biosciences. "IFx-2.0’s potential ability to harness the power of a patient’s innate immune response leading to the activation and proliferation of tumor specific B cells and T cells represents a novel mechanism to overcome primary resistance to checkpoint inhibitors. As we start initiating study sites, we are grateful for the interest among investigators from leading cancer centers across the US in participating in this Phase 3 trial. We anticipate having more than half of the 22 participating sites open over the next 3-4 weeks, with the balance activated by the end of summer."

The Company’s Phase 3 accelerated approval trial of IFx-2.0, conducted under an SPA Agreement with the U.S. FDA, will evaluate IFx-2.0 as an adjunctive therapy administered weekly for three weeks concurrent with the approved dose and schedule for Keytruda compared to Keytruda plus placebo in the first line treatment for patients with advanced or metastatic MCC. Keytruda is currently approved in MCC under accelerated approval based on ORR. The pivotal trial for IFx-2.0 is expected to enroll 118 participants across approximately 22 to 25 U.S. sites. Trial participants will be randomized on a 1:1 basis and receive Keytruda in both arms, for up to two years, or until disease progression or Keytruda related toxicities. The primary endpoint for the trial is ORR with a key secondary endpoint of PFS. Other secondary endpoints are safety, duration of response, and overall survival. Accelerated approval is based on the successful achievement of the ORR primary endpoint. The key secondary endpoint of PFS, if successfully achieved without a detrimental effect on overall survival, could satisfy the requirement for regular approval without the requirement for a post approval confirmatory trial.

The initiation of the Phase 3 trial represents the achievement of a milestone for the third tranche of funding under the Company’s recently announced private placement, thereby trigging the purchase from the Company of an additional $2.23 million under the private placement financing.

On June 24, 2025 Verastem Oncology (Nasdaq: VSTM), a biopharmaceutical company committed to advancing new medicines for patients with RAS/MAPK pathway-driven cancers, reported that the first patient has been dosed in VS-7375-101, the U.S. Phase 1/2a clinical trial evaluating VS-7375, a potential best-in-class oral KRAS G12D (ON/OFF) inhibitor, in patients with advanced KRAS G12D mutant solid tumors (Press release, Verastem, JUN 24, 2025, View Source [SID1234654094]).

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!

"We continue to make strong progress against our strategic priorities and key milestones that we set at the beginning of the year, including our recent FDA approval and commercial launch and our positive updated results and trial expansion in first-line metastatic pancreatic cancer. We are now excited to have achieved another milestone with the initiation of our first clinical trial and first patient dosed with VS-7375, a potential best-in-class oral KRAS G12D (ON/OFF) inhibitor, in the U.S.," said Dan Paterson, president and chief executive officer of Verastem Oncology.

VS-7375-101 is a Phase 1/2a study being conducted in the U.S., with plans to expand globally, and will evaluate the safety and efficacy of VS-7375 in patients with advanced KRAS G12D mutant solid tumors. The monotherapy dose escalation phase of the study will use a starting dose of 400 mg, based on an efficacious dose identified in the Phase 1/2 study conducted in China by the Company’s partner, GenFleet Therapeutics. GenFleet announced encouraging initial safety and efficacy results from its Phase 1 dose-escalation phase of its study of VS-7375 (known as GFH375 in China) at the 2025 ASCO (Free ASCO Whitepaper) Annual Meeting. Verastem plans to dose-escalate across dose levels where encouraging initial safety and efficacy were observed in patients with advanced KRAS G12D mutant solid tumor cancers in GenFleet’s study. Upon successful completion of the dose-escalation phase, the Company will select a recommended Phase 2 dose and assess the efficacy and safety of monotherapy VS-7375 in expansion cohorts of patients with advanced pancreatic cancer and non-small cell lung cancer. In parallel with the monotherapy dose escalation, Verastem will evaluate VS-7375 in combination with cetuximab in advanced solid tumors. Subject to the results of the Phase 1 dose escalation combination of VS-7375 and cetuximab, Verastem plans to initiate a combination expansion cohort in colorectal cancer.

"We are excited that the first patient has initiated treatment with VS-7375 in the U.S. We believe we can leverage VS-7375’s dual inhibition of both the ON/OFF states to improve on the efficacy seen to date with other KRAS G12D-selective agents. With the trial underway, we aim to accelerate the program’s development given the lack of FDA-approved, KRAS G12D-targeted treatments available to patients with KRAS G12D cancers," said John Hayslip, M.D., chief medical officer of Verastem Oncology. "We are strongly encouraged by the anti-tumor activity seen in the updated Phase 1 data presented at the ASCO (Free ASCO Whitepaper) Annual Meeting from our partner GenFleet Therapeutics’ trial in China. We are advancing VS-7375 in the U.S. to target KRAS G12D mutant advanced solid tumors in areas of significant unmet need, such as pancreatic, colorectal, and lung cancers."

About KRAS G12D

KRAS G12D represents 26% of all KRAS mutations, making it the most prevalent KRAS mutation in human cancers. The KRAS G12D mutation occurs most commonly in pancreatic (37%), colorectal (12.5%), endometrial (8%), and non-small cell lung (5%) cancers. Currently, no therapies are approved by the U.S. Food and Drug Administration (FDA) specifically targeting KRAS G12D mutations in cancer.

About VS-7375, an Oral KRAS G12D (ON/OFF) Inhibitor

VS-7375 is a potential best-in-class, potent, and selective oral KRAS G12D dual ON/OFF inhibitor. VS-7375 is the lead program from the Verastem Oncology discovery, development, and commercialization collaboration with GenFleet Therapeutics. Verastem announced in April 2025 that the U.S. Investigational New Drug (IND) application for VS-7375 was cleared, and it initiated a Phase 1/2a clinical trial (NCT07020221), VS-7375-101, in May 2025. GenFleet’s IND for VS-7375 (known as GFH375 in China) was approved in China in June 2024, and initial safety and efficacy results from the Phase 1 portion of the study were announced at ASCO (Free ASCO Whitepaper) 2025. In February 2025, GenFleet announced that the first patient was dosed in the Phase 2 portion of the study.

On June 24, 2025 Hoth Therapeutics reported it will host a Key Opinion Leader (KOL) event on, at 3:30PM EST to highlight recent clinical progress with HT-001, a novel topical therapeutic developed to address EGFR inhibitor-induced skin toxicities in cancer patients (Press release, Hoth Therapeutics, JUN 24, 2025, View Source [SID1234654095]). This event will feature insights from derm-oncology and dermatology specialists Jonathan Hale Zippin M.D., Ph.D., and Adam Friedman M.D., F.A.A.D., who will present interim results from the ongoing Phase 2 trial and discuss how HT-001 could redefine supportive care standards for oncology patients. Access/join the event through the following link: View Source

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!

Phase 2a Trial Highlights (CLEER-001)

100% of enrolled patients in open-label cohort achieved at least one primary endpoint of clinical dermatologic improvement
Over 65% reported reductions in pain and pruritus (itching)
0% required dose reduction or discontinuation of their EGFRI therapy.
Topical therapy was well tolerated with no serious adverse events.
NEW YORK, June 24, 2025 /PRNewswire/ — Hoth Therapeutics, Inc. (NASDAQ: HOTH), a clinical-stage biopharmaceutical company developing targeted therapies for rare and serious inflammatory conditions, reported that its investigational candidate HT-001 met the primary efficacy endpoint in at least one metric in 100% of patients in its ongoing Phase 2a clinical study (CLEER-001) evaluating treatment for epidermal growth factor receptor inhibitor (EGFRI)-induced cutaneous toxicities.

EGFR inhibitors, used widely to treat non-small cell lung cancer (NSCLC), pancreatic, breast, colorectal, and head and neck cancers, are associated with dermatologic side effects in up to 90% of patients, often resulting in painful rashes, pruritus, dryness, nail changes, and alopecia. These adverse events frequently force dose reductions or treatment discontinuation, limiting therapeutic efficacy and patient outcomes.

"HT-001 is a breakthrough candidate with the potential to be the first FDA-approved therapy specifically targeting these EGFRI-related skin toxicities," said Robb Knie, CEO of Hoth Therapeutics. "The ability to preserve full-dose cancer treatment while improving patient quality of life addresses a critical unmet need across oncology."

Phase 2a Trial Highlights (CLEER-001)

100% of enrolled patients in open-label cohort achieved at least one primary endpoint of clinical dermatologic improvement
Over 65% reported reductions in pain and pruritus (itching)
0% required dose reduction or discontinuation of their EGFRI therapy.
Topical therapy was well tolerated with no serious adverse events.
HT-001 is a once-daily topical gel formulated with an FDA-approved neurokinin-1 receptor antagonist (NK1RA). This mechanism mitigates inflammatory pathways triggered by EGFR inhibition, particularly Substance P-driven responses that lead to skin breakdown. By targeting the neuroinflammatory axis, HT-001 reduces symptoms without immunosuppression or systemic toxicity.

Supporting Preclinical Data

In preclinical rat models co-treated with erlotinib (5.85 mg/kg/day), HT-001 significantly reduced:

Dermatitis and alopecia severity
Inflammatory markers including Substance P and neutrophil activity
Disease progression even when HT-001 was introduced after symptom onset.
Additionally, in compassionate-use human cases, complete symptom resolution was observed within one week, with no recurrence for up to three weeks post-treatment discontinuation.

Regulatory and Development Pathway

HT-001 is being advanced under the 505(b)(2) regulatory pathway, enabling the use of existing safety data to accelerate development. Key milestones include:

IND opened and chronic toxicology completed.
Phase 2a trial (CLEER-001) currently underway in the U.S.
Phase 2b/3 trial planning in progress

On June 24, 2025 Accord Healthcare Limited (Accord) reported that the anti-PD-1 mAb, serplulimab, marketed as Hetronifly, has been approved by the MHRA to treat adults in the UK with extensive-stage small cell lung cancer (ES-SCLC), which has not previously been treated and has spread within the lungs or to other parts of the body (Press release, Accord Healthcare, JUN 24, 2025, View Source [SID1234654096]).

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!

This approval comes in the same week as the announcement in India, bringing the total number of countries and regions in which the medicine is approved to over 40 — including Europe, China, Indonesia, and Singapore. Accord Healthcare will lead commercialisation in both the UK and India on behalf of its parent company, Intas, and its commercial partner, Henlius.

Lung cancer remains the leading cause of cancer-related death globally. Small cell lung cancer (SCLC), one of the most aggressive subtypes, accounts for approximately 15% of all lung cancer cases and is associated with limited treatment options[1].

Julian Beach, Interim Executive Director of Healthcare Quality and Access at the UK’s Medicines and Healthcare products Regulatory Agency (MHRA), commented: "As the first and only anti-PD-1 monoclonal antibody approved in the UK for small cell lung cancer, this marks an important new treatment option for patients with this aggressive type of lung cancer who currently have limited choices and face a poor prognosis."[2]

Henlius Biotech originally developed Serplulimab. In 2023, Henlius entered into a collaboration with Intas Pharmaceuticals, granting Intas exclusive rights to develop and commercialise the medicine in over 50 countries across Europe and India.

Welcoming the news, Paul Tredwell, Executive Vice-President EMENA, Accord Healthcare, said: "At Accord, we are dedicated to supporting patients with cancer. The MHRA’s approval of Hetronifly provides a new treatment option in the fight against extensive-stage small cell lung cancer — one of the most aggressive forms of lung cancer. This milestone reflects our ongoing commitment to providing novel specialty medicines for difficult-to-treat conditions."

Ping Cao, Chief Business Development Officer and Senior Vice President of Henlius said: "The approvals of serplulimab in the UK and India not only represent continued progress in our globalisation strategy but also reflect our concrete commitment to putting patients first. We are steadily expanding the global reach of the product, aiming to bring high-quality innovative therapies to more patients around the world."

In December 2022, serplulimab received orphan drug designation from the EC for the treatment of SCLC, this was recently reviewed by the committee and renewed.

ESMO has also scored serplulimab 4 out of 5 on their magnitude of clinical benefit scale (MCBS) in ES-SCLC.

About Serplulimab

Serplulimab (recombinant humanised anti-PD-1 monoclonal antibody injection)) is an anti-PD-1 mAb for the first-line treatment of SCLC and has been approved in China and several SEA countries. Serplulimab has been approved by the National Medicinal Products Administration (NMPA) in China for the treatment of squamous non-small cell lung cancer (sqNSCLC), extensive-stage small cell lung cancer (ES-SCLC), esophageal squamous cell carcinoma (ESCC) and non-squamous non-small cell lung cancer (nsNSCLC). Serplulimab was granted orphan drug designations by the FDA and the EC for the treatment of SCLC, and its bridging head-to-head trial in the United States to compare serplulimab to standard of care atezolizumab (anti-PD-L1 mAb) for the first-line treatment of ES-SCLC is well under way.

The results of 4 pivotal trials of serplulimab were published in the Journal of the American Medical Association (JAMA), Nature Medicine, Cancer Cell and British Journal of Cancer, respectively. Furthermore, serplulimab was respectively recommended by the CSCO Guidelines for Small Cell Lung Cancer, the CSCO Guidelines for Non-Small Cell Lung Cancer, the CSCO Guidelines for Esophageal Cancer, the CSCO Clinical Practice Guidelines on Immune Checkpoint Inhibitor, the China Guidelines for Radiotherapy of Esophageal Cancer, and other definitive guides, providing valuable references for clinical diagnosis and treatment of tumours.

The approvals were primarily based on the results of the global phase 3 clinical study ASTRUM-005, which enrolled 585 patients across 128 trial sites worldwide. At the 2025 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, the results from the final analysis of ASTRUM-005 were presented, showing a median follow-up of 42.4 months and a 4-year overall survival (OS) rate of 21.9% (95% CI: 17.6–26.6%) for the serplulimab plus chemotherapy group. These results further confirm the long-term survival benefit of this immunotherapy-based regimen for patients with ES-SCLC.

About Lung Cancer

Lung cancer is the most common cancer worldwide in terms of incidence and mortality. According to GLOBOCAN 2022, there were over 2.48 million new cases of lung cancer globally in 2022, accounting for 12.4% of all new cancer cases.[1]

Small cell lung cancer (SCLC), which accounts for 15% to 20% of all lung cancers, is characterised by high malignancy, early metastasis, rapid progression, and poor prognosis.

Among SCLC patients, approximately 30% to 40% are diagnosed at a limited stage, while the remaining cases are in an extensive stage.

Within Europe, the prevalence of SCLC ranges from 1 to 5 per 10,000 people.

On June 23, 2025 Leap Therapeutics, Inc. (Nasdaq:LPTX), a biotechnology company focused on developing targeted and immuno-oncology therapeutics, reported updated results from Part B of the DeFianCe study (NCT05480306), a Phase 2 study of sirexatamab (DKN-01), an anti-DKK1 monoclonal antibody, in combination with bevacizumab and chemotherapy (Sirexatamab Arm) compared to bevacizumab and chemotherapy (Control Arm) in patients with advanced microsatellite stable (MSS) colorectal cancer (CRC) who have received one prior systemic therapy for advanced disease (Press release, Leap Therapeutics, JUN 23, 2025, View Source [SID1234654056]). Due to the Company’s financial position, Leap’s Board of Directors is taking further steps to preserve capital and has initiated a process to explore strategic options to preserve and maximize shareholder value.

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!

"Sirexatamab demonstrated a statistically significant benefit in patients with high levels of DKK1, no prior exposure to anti-VEGF therapy, or liver metastasis, with a positive trend on ORR and PFS in the full second-line CRC population. With the additional patient follow-up, we believe that the objectives of the DeFianCe study have been achieved. On behalf of everyone at Leap, I thank all the patients and physicians who have participated in our sirexatamab clinical trials," said Douglas E. Onsi, President and Chief Executive Officer of Leap. "However, due to current market conditions, we have decided to wind-down the DeFianCe clinical trial and further reduce internal expenses. In parallel, we have initiated a review of the full range of strategic alternatives to maximize shareholder value."

DeFianCe Study Update

In the updated analysis as of May 22, 2025, sirexatamab demonstrated a positive trend on overall response rate (ORR), by investigator assessment (IA) and blinded independent central review (BICR), and progression-free survival (PFS) in the full second-line CRC population, driven by the statistically significant benefit in patients with high levels of DKK1, no prior exposure to anti-VEGF therapy, or liver metastasis.

· Across the intent-to-treat population (n=188):

Sirexatamab Arm
(n=94) Control Arm
(n=94)
Median PFS 9.2 months 8.31 months HR 0.84
95% CI: 0.57, 1.22
p = 0.1749
ORR by IA 35.1% 26.6% p = 0.1009
ORR by BICR 33.0% 20.2% P = 0.0203
Remaining on study drug 21 15

· In patients with high DKK1 levels (upper quartile, n=44):

Sirexatamab Arm
(n=25) Control Arm
(n=19)
Median PFS 9.36 months 5.88 months HR 0.47
95% CI: 0.22, 1.01
p = 0.0237
ORR by IA 44.0% 15.8% p = 0.0149
ORR by BICR 40.0% 15.8% p = 0.0301
Median OS Not Yet Reached 9.66 months HR 0.19
95% CI: 0.05, 0.73
p = 0.0037
Remaining on study drug 7 1

· In patients with DKK1 levels above the median (upper median, n=88):

Sirexatamab Arm
(n=50) Control Arm
(n=38)
Median PFS 9.03 months 7.23 months HR 0.56
95% CI: 0.33, 0.94
p = 0.0146
ORR by IA 38.0% 23.7% p = 0.0706
ORR by BICR 40.0% 15.8% p = 0.0039
Median OS Not Yet Reached 14.39 months HR 0.48
95% CI: 0.2, 1.16
p = 0.0475
Remaining on study drug 12 3

· In patients who had not received prior anti-VEGF therapy (n=95):

Sirexatamab Arm
(n=49) Control Arm
(n=46)
Median PFS 11.2 months 8.34 months HR 0.61
95% CI: 0.35, 1.06
p = 0.0383
ORR by IA 55.1% 32.6% p = 0.0116
ORR by BICR 44.9% 26.1% p = 0.0252
Median OS Not Yet Reached Not Yet Reached HR 0.47
95% CI: 0.14, 1.6
p = 0.1069
Remaining on study drug 15 5

· In patients with liver metastases (n=138):

Sirexatamab Arm
(n=73) Control Arm
(n=65)
Median PFS 9.03 months 7.26 months HR 0.7
95% CI: 0.46, 1.06
p = 0.0443
ORR by IA 37.0% 27.7% p = 0.1203
ORR by BICR 30.1% 24.6% p = 0.233
Median OS Not Yet Reached 15.74 HR 0.69
95% CI: 0.33, 1.43
p = 0.1584
Remaining on study drug 14 6

Corporate Update

Leap is taking additional steps to reduce spending and preserve capital. Over the next two months as the DeFianCe study completes, the Company will implement a workforce reduction of approximately 75%. The total cash payments and costs related to this reduction in force, including severance payments, are estimated to be approximately $3.2 million. The majority of these costs will be recognized in the third quarter of 2025. The Company’s cash and cash equivalents totaled $32.7 million as of March 31, 2025.

Leap has initiated a process to explore strategic alternatives to preserve and maximize shareholder value, including leveraging its cash balance and exploring potential sale or partnership opportunities for sirexatamab and FL-501. The Company’s Board of Directors has approved the engagement of Raymond James & Associates, Inc. to serve as exclusive financial advisor to assist in the strategic evaluation process.