On June 2, 2025 Innovent Biologics, Inc. ("Innovent") (HKEX: 01801), a world-class biopharmaceutical company that develops, manufactures and commercializes high-quality medicines for the treatment of oncology, cardiovascular and metabolic, autoimmune, ophthalmology and other major diseases, reported updated Phase 1 study results of IBI343, a novel anti-CLDN18.2 ADC, for the treatment of advanced pancreatic cancer at the 2025 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting (Press release, Innovent Biologics, JUN 2, 2025, View Source [SID1234653637]).

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With extended follow-up and more mature data on progression-free survival (PFS) and overall survival (OS), IBI343 has demonstrated promising therapeutic efficacy in patients with CLDN18.2-positive advanced pancreatic cancer. These encouraging results suggest the potential of IBI343 in this challenging-to-treat malignancy. Supported by these robust clinical findings, IBI343 has been granted Breakthrough Therapy Designation (BTD) by China’s National Medical Products Administration (NMPA). Concurrently, the Phase 1 clinical trial of IBI343 is also being conducted in the United States, where the drug candidate has received Fast Track Designation (FTD) from the U.S. Food and Drug Administration (FDA).

Pancreatic cancer is one of the most aggressive malignancies worldwide. Most patients are diagnosed in the middle and late stages and often develop resistance to standard chemotherapy, resulting in a 5-year survival rate of less than 10%1. According to the GLOBOCAN 2022 statistics2, there are approximately 510,000 new cases and 467,000 deaths globally from pancreatic cancer each year, with China accounting for 120,000 new cases and 110,000 deaths annually.

This Phase 1/1b study is a multi-regional, dose escalation and expansion clinical trial (NCT05458219). Preliminary data were presented at ASCO (Free ASCO Whitepaper) 2025 and ESMO (Free ESMO Whitepaper) Asia 2024 and the updated results from the study’s dose-expansion cohort were presented at the 2025 ASCO (Free ASCO Whitepaper) as follows:

As of March 14, 2025, a total of 83 patients with pancreatic cancer had received at least one dose of IBI343 with a median follow-up time of 11.1 months.
As the data cutoff date, in patients with CLDN18.2 1+2+3+≥60% expression treated at the 6mg/kg dose (N=44), the confirmed overall objective response rate (cORR) was 22.7% and the disease control rate (DCR) was 81.8%. The median progression-free survival (mPFS) was 5.4 months, and the median overall survival (mOS) was 9.1 months. Among them, 17 patients had received only one line of prior treatment, achieving a mPFS of 5.4 months and a mOS of 12.1 months; and 18 patients had received two lines of prior treatment, the mPFS was 5.3 months and the mOS was 9.1 months.
The updated safety results demonstrated the favorable safety profile of IBI343 with a consistently low rate of gastrointestinal toxicity and no new safety signals. 98.8% of the patients experienced treatment-emergent adverse events (TEAEs), with the most common TEAEs being anemia, neutrophil count decreased, and white blood cell count decreased. Notably, no ≥ grade 3 nausea and vomiting occurred.
Professor Xianjun Yu from Fudan University Cancer Hospital, said, "Pancreatic cancer is one of the most malignant tumors of the digestive tract. Most patients are already in the advanced stage when diagnosed, and the 5-year survival rate is only about 10%1. Currently, chemotherapy is still the main first- and second-line treatment for advanced pancreatic cancer. The clinical options for second-line treatment are particularly limited, with a chemotherapy response rate of only 6-16%, median progression free survival of 2 to 5 months, and a median survival of approximately 6 to 9 months3, representing an urgent clinical need. With longer follow-up, the mature PFS and OS data from the latest IBI343 update demonstrate promising therapeutic potential, suggesting a breakthrough in this difficult-to-treat malignancy."

Dr. Hui Zhou, Senior Vice President of Innovent, said, "We are pleased to present an oral update on IBI343’s clinical data at this year’s ASCO (Free ASCO Whitepaper) conference. With the unique Fc-silent antibody design, stable linker and potent TOPO1i payload, IBI343 is the first ADC candidate to show encouraging efficacy and a favorable safety profile in the treatment of advanced pancreatic cancer. We hope to continue advancing the clinical trials of IBI343 for pancreatic cancer patients. Innovent will leverage its unique strengths in R&D innovation and clinical translation to develop a new generation of globally competitive oncology – focused innovative pipeline to benefit patients worldwide.."

About IBI343（Anti-CLDN18.2 ADC）

IBI343 is a recombinant human anti-CLDN18.2 monoclonal antibody-drug conjugate (ADC) developed by Innovent Biologics. IBI343 binds to the CLDN18.2-expressing tumor cells, the CLDN18.2 dependent ADC internalization will occur and the drug is released resulting in DNA damage and eventually apoptosis of the tumor cells. The freed drug can also diffuse across the plasma membrane to reach and kill the neighboring cells, resulting in "bystander killing effect".

As an innovative TOPO1i ADC, IBI343 has demonstrated tolerable safety and encouraging efficacy signals in Phase 1 clinical studies. The therapeutic potential of IBI343 is currently being explored in tumor types such as gastric and pancreatic cancer.

The Phase 3 trial of IBI343 for advanced gastric / gastroesophageal junction adenocarcinoma is now recruiting patients. The relevant indication has been included in China’s NMPA breakthrough therapy list.

IBI343’s Phase 1 trial for advanced pancreatic ductal adenocarcinoma is enrolling patients in an multi-regional study. This indication has received Fast Track designation from the FDA and been included in the NMPA’s BTD list.

On June 2, 2025 Innovent Biologics, Inc. ("Innovent") (HKEX: 01801), a world-class biopharmaceutical company that develops, manufactures and commercializes high-quality medicines for the treatment of oncologic, autoimmune, cardiovascular and metabolic, ophthalmologic and other major diseases, reported updated clinical data of IBI354 (HER2 monoclonal antibody-camptothecin derivative conjugate) in advanced solid tumors at the 2025 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting (Press release, Innovent Biologics, JUN 2, 2025, View Source [SID1234653636]).

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IBI354 has demonstrated promising anti-tumor efficacy and favorable safety profiles across multiple solid tumors. It not only holds potential to deliver a new generation of ADC therapies characterized by "high potency and low-toxicity" for tumor types such as ovarian cancer and breast cancer, but also validates the advantages of Innovent’s ADC technology platform. The results of IBI354 lays the foundation for the subsequent development of Innovent’s next-generation of bispecific ADCs and dual-payload ADCs, marking a milestone in Innovent’s next-generation "IO+ADC" oncology development strategy.

The data presented is from a Phase 1/2 clinical study (NCT05636215) aimed at evaluating the safety, tolerability, and preliminary efficacy of IBI354 in participants with advanced solid tumors. As of March 24, 2025, a total of 368 participants with advanced solid tumors were enrolled and received different doses of IBI354 monotherapy, the median follow-up duration was 11.5 months (range: 0.7-19.6), the median treatment duration was 27.0 weeks (range: 3.1-81.3) and 74 (20.1%) pts were still on treatment. The tumor types including 178 with breast cancer, 92 with ovarian cancer, 38 with colorectal cancer, and 60 with other tumors.

IBI354 monotherapy demonstrated excellent safety profile

The dosage was escalated to 18mg/kg, with no DLT events observed.
The most common treatment-related adverse events (TRAEs) were anemia, nausea, and white blood cell count decreased. The incidence of interstitial lung disease (ILD) was only 1.9%, all were grade 1-2.
Overall, 27.4% of patients experienced TRAEs ≥ grade 3, 17.7% experienced TRAEs leading to dose interruption, 2.7% experienced TRAEs leading to dose reduction and 1.6% experienced TRAEs leading to discontinuation, with no TRAEs leading to death.
IBI354 monotherapy showed promising efficacy signals in multiple tumor types

In HER2-positive breast cancer cohort (n= 88, treated at 6~15mg/kg, the median prior treatment lines was 4), the confirmed objective response rate (ORR) and the disease control rate (DCR) were 59.1% and 90.9%, respectively. In 9 mg/kg Q3W subgroup (n=29), the ORR and the DCR were 72.4% and 89.7%, respectively. The median progression-free survival (PFS) was 14.1 months (95% CI: 8.3-not calculable [NC]) with events of 48.3%. The median overall survival (OS) was immature with events of 3.4%.
In ovarian cancer cohort (n=92, treated at 2~12mg/kg, the median prior treatment lines was 3), the cORR was 41.2% and the DCR was 82.0%. In the 12mg/kg Q3W subgroup (n=40), the cORR reached 55.0% and the DCR was 90.0%. In participants with HER2 1+ (n=27), the ORR reached 55.6% and the DCR was 88.9%. As of the data cutoff date, the median follow-up time was 11.9 months, and the median PFS was 7.1 months (95% CI: 5.2−10.8) in 12mg/kg Q3W dose group. The median OS was not mature with events in 14 (34.1%) pts and a 12-month OS rate of 63.9% (95% CI: 45.0−77.8).
Professor Qi Zhou, Chief Physician at the Gynecologic Oncology Center of Chongqing University Affiliated Cancer Hospital and the Principal Investigator of the gynecologic oncology cohort study, stated, "The treatment of platinum-resistant recurrent ovarian cancer is difficult and the prognosis is poor, threatening the life and health of women. Extending PFS and OS in platinum-resistant recurrent ovarian cancer patients remains a clinical challenge for gynecological oncologists. ADC drugs provide a new direction for overcoming resistance mechanisms by precisely delivering cytotoxic agents. HER2, as a validated solid tumor target, has made breakthroughs in breast and gastric cancer fields, while the novel ADC drug IBI354 shows broad-spectrum antitumor activity through unique design in HER2 low-expression (IHC 1+) platinum-resistant ovarian cancer. In the Phase 1 study with a dose of 12mg/kg Q3W, IBI354 demonstrated an ORR of 55.0% and DCR of 90.0%, with a median PFS reaching 7.1 months. The safety profile was very good without common severe interstitial lung disease or ocular toxicity seen in other ADCs. These results significantly outperform traditional chemotherapy regimens, suggesting its potential breakthrough efficacy in the platinum-resistant population. The Phase 3 study of IBI354 in platinum-resistant ovarian cancer (HeriCare-Ovarian01) has been initiated, and I am looking forward to the results, as well as the further validation of the long-term benefits for patients receiving IBI354."

Doctor Charlotte Rose Lemech from Scientia Clinical Research Ltd, Australia, stated: "Breast cancer is one of the most common malignant tumors among women globally and remains a leading cause of cancer-related deaths. The amplification or overexpression of HER2 (human epidermal growth factor receptor 2) is recognized as a key driver in the development, progression, and metastasis of breast cancer, with approximately 15%-20% of breast cancer patients exhibiting HER2 overexpression. ADCs have become the new standard treatment for later line HER2 positive breast cancer. In this Phase 1 study, IBI354 has demonstrated encouraging efficacy and safety data, achieving high ORR and DCR especially in 9 mg/kg Q3W subgroup. Long term survival was also achieved with the median PFS of 14.1 months. IBI354 also differentiates itself from other HER2 targeted therapies with its safety profile. The incidence of interstitial lung disease was extremely low and most of the hematological toxicity and gastrointestinal adverse events were mild to moderate and can be effectively managed with standard supportive care. This favorable safety profile enhances the clinical application potential of IBI354 and we look forward to IBI354 achieving more breakthroughs in the field of breast cancer treatment."

Dr. Hui Zhou, Senior Vice President of Innovent, stated: "With the rapid development of ADC drugs in the field of tumor treatment, Innovent is steadily advancing its strategic layout in the ADC field. At this year’s ASCO (Free ASCO Whitepaper) conference, we update the safety and efficacy data of IBI354 across various advanced solid tumors. These clinical results not only confirm the potential therapeutic value of IBI354 but also demonstrating Innovent’s innovative strength and technological advantages in ADC drug development. The phase 3 study of IBI354 in platinum-resistant ovarian cancer has been initiated, and more clinical studies are also planned. We will continue to invest in next-generation ADC molecules, aiming to address unmet clinical needs and bring patients with more effective and safer treatment options."

About IBI354 (Anti-HER2 Antibody-Camptothecin Derivative Conjugate)

IBI354 is an innovative HER2-targeted antibody–camptocinin derivative conjugate developed by Innovent’s proprietary SoloTx ADC platform. With a drug-to-antibody ratio (DAR) of 8, IBI354 delivers a high payload of effective drugs to tumors. The highly hydrophilic linker design contributes to its excellent biophysical and pharmacokinetic (PK) properties, while the hydrophobic payload enhances its bystander effect, targeting adjacent antigen-low or negative tumor cells. IBI354 exhibits extremely low exposure of free toxin in circulation and has an ideal safety profile based on pre-clinical and clinical studies. IBI354 has demonstrated remarkable anti-tumor activity in various tumor-bearing mice models, particularly in those resistant to HER2-targeted therapies and in metastatic tumors. Innovent Biologics is conducting clinical studies to assess the efficacy and safety of IBI354 for multiple advanced solid tumors.

On June 2, 2025 Verastem Oncology (Nasdaq: VSTM), a biopharmaceutical company committed to advancing new medicines for patients with RAS/MAPK pathway-driven cancers, reported positive updated data from the dose escalation phase of the Phase 1/2 trial of GFH375 (known as VS-7375 in the U.S.). As of May 16, 2025, 23 efficacy-evaluable patients with pancreatic ductal adenocarcinoma (PDAC) and 12 efficacy-evaluable patients with non-small cell lung cancer (NSCLC) achieved an overall response rate (ORR) of 52% and 42%, respectively (Press release, Verastem, JUN 2, 2025, View Source [SID1234653635]). The updated data were presented by Verastem’s partner, GenFleet Therapeutics, in a rapid oral presentation at the 2025 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting on June 2, 2025, in Chicago, IL.

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"We are encouraged by the initial efficacy and safety results from the Phase 1 portion of the study of GFH375 in China by our partner, GenFleet Therapeutics. The results presented at ASCO (Free ASCO Whitepaper) further support our advancement of our clinical program for VS-7375 in the U.S., as we believe there remains a significant opportunity to further improve on the efficacy seen to date with other KRAS G12D-selective agents. VS-7375’s dual inhibition of both the ON/OFF states has the potential to drive deep and durable cancer responses and allow for better combinability with other agents," said Dan Paterson, president and chief executive officer of Verastem Oncology.

ASCO 2025 Presentation Highlights

GenFleet reported that 62 patients were enrolled in the Phase 1 portion of the study in China, receiving oral doses ranging from 100 to 900 mg daily. In the study, 98% of patients had metastatic disease, and 75% had received ≥2 prior lines of therapy. As of the data cutoff of May 16, 2025, 23 efficacy-evaluable patients with PDAC and 12 efficacy-evaluable patients with NSCLC, who received daily dosages of 400 or 600 mg and had at least one post-treatment tumor assessment, achieved an ORR of 52% and a disease control rate (DCR) of 100%, and an ORR of 42% and a DCR of 83%, respectively.

As of the cutoff date of March 31, 2025, GenFleet reported that there were no dose-limiting toxicities (DLTs) observed across all dose levels (100-900 mg QD), and the treatment-related adverse events (TRAEs) were mostly Grade 1/2. The most common TRAEs occurring in at least 20% of patients were diarrhea, nausea, vomiting, and anemia. TRAEs ≥ Grade 3 consisted mainly of decreased neutrophil count (8%) and diarrhea (5%). No TRAE-related deaths were reported.

Webcast Information

Verastem will hold an investor webcast on Monday, June 2, at 11:00 am CDT, to review the RAMP 205 updated data and the VS-7375 program including updated data from the study in China. The event will feature members of Verastem’s management team and key opinion leaders. A live audio webcast of the call, along with accompanying slides, will be accessible here. A replay of the webcast will be archived on the website for approximately 90 days following the presentation.

U.S. Phase 1/2a Study of VS-7375

The Phase 1/2a study will be conducted in the U.S., with the potential to expand globally, and will evaluate the safety and efficacy of VS-7375 in patients with advanced KRAS G12D mutant solid tumors. The starting dose for the Phase 1 study of 400 mg is based on the dose identified in the initial data from the GenFleet study to accelerate the trial’s progress. Verastem plans to dose escalate across levels where responses were observed in GenFleet’s study and will assess in the Phase 2a portion the efficacy and safety of VS-7375, both as monotherapy and in combination, in patients with advanced solid tumors, such as pancreatic, colorectal, and non-small cell lung cancers.

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 and development collaboration with GenFleet Therapeutics. Verastem announced in April 2025 that the U.S. Investigational New Drug (IND) application for VS-7375 was cleared and plans to initiate a Phase 1/2a clinical trial in mid-2025. GenFleet’s IND for VS-7375 (known as GFH375 in China) was approved in China in June 2024, and the first patient was dosed in a Phase 1/2 study in July 2024.

On June 2, 2025 Astrazeneca and Daiichi sankyo reported positive results from the DESTINY-Breast09 Phase III trial showed Enhertu (trastuzumab deruxtecan) plus pertuzumab demonstrated a highly statistically significant and clinically meaningful improvement in progression-free survival (PFS) compared to a taxane, trastuzumab and pertuzumab (THP) as a 1st-line treatment for patients with HER2-positive metastatic breast cancer (Press release, AstraZeneca, JUN 2, 2025, View Source [SID1234653634]).

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Results will be presented today during a special late-breaking oral session at the 2025 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in Chicago, IL (abstract #LBA1008).

In a prespecified interim analysis, Enhertu plus pertuzumab reduced the risk of disease progression or death by 44% versus THP (based on a hazard ratio [HR] of 0.56; 95% confidence interval [CI] 0.44-0.71; p<0.00001). Median PFS was 40.7 months with Enhertu plus pertuzumab compared to 26.9 months for THP, as assessed by blinded independent central review (BICR). The PFS benefit for Enhertu plus pertuzumab versus THP was consistent across subgroups, including for the prespecified stratification factors of de novo or recurrent disease, hormone receptor status and PIK3CA mutation status.

Investigator-assessed PFS demonstrated a median PFS of 40.7 months for Enhertu plus pertuzumab compared to 20.7 months for THP (HR 0.49; 95% CI 0.39-0.61; nominal p-value <0.00001).

Confirmed objective response rate (ORR) with Enhertu plus pertuzumab was 85.1% versus 78.6% with THP. There were 58 complete responses (CRs) with Enhertu plus pertuzumab compared to 33 with THP. Median duration of response (DOR) for Enhertu plus pertuzumab exceeded three years (39.2 months) versus 26.4 months with THP.

Overall survival (OS) was not mature at the time of the interim analysis (16% maturity at data cut-off); however, interim OS data showed an early trend favouring the Enhertu combination compared to THP (HR 0.84; 95% CI 0.59-1.19).

Sara Tolaney, MD, MPH, Chief of the Division of Breast Oncology, Dana-Farber Cancer Institute and principal investigator in the trial, said: "Patients with HER2-positive metastatic breast cancer often experience disease progression around two years after initiating standard-of-care first-line treatment. With a median progression-free survival of more than three years, the DESTINY-Breast09 results show trastuzumab deruxtecan combined with pertuzumab has the potential to become a new first-line standard of care for these patients."

Susan Galbraith, Executive Vice President, Oncology Haematology R&D, AstraZeneca, said: "Bringing Enhertu earlier in the treatment of HER2-positive metastatic breast cancer may represent an important advancement for patients. The DESTINY-Breast09 trial showed the combination of Enhertu and pertuzumab in the first-line setting substantially increased the amount of time before a patient’s cancer progressed compared to standard of care and nearly doubled the number of patients showing no signs of disease on imaging. Establishing a strong therapeutic response as soon as metastatic disease is diagnosed is critical given that about one in three patients do not receive further treatment after progressing in the first-line setting."

Ken Takeshita, Global Head, R&D, Daiichi Sankyo, said: "Enhertu continues to transform the treatment of metastatic breast cancer with the first new data in more than a decade to demonstrate improved outcomes for a broad population of patients with HER2-positive disease compared to THP in the first-line setting. DESTINY-Breast09 shows that initiating treatment with Enhertu in combination with pertuzumab at the time of metastatic diagnosis can delay disease progression."

Summary of DESTINY-Breast09 interim analysis results

Efficacy Measure

Enhertu (5.4 mg/kg) + pertuzumab

(n=383)

THP

(n=387)

PFS by BICRi

Median PFS (months) (95% CI)

40.7

(36.5-NC)

26.9

(21.8-NC)

Hazard ratio (95% CI)

HR 0.56 (0.44-0.71)

p-value

p<0.00001ii

24-month PFS rate (%) (95% CI)

70.1

(64.8-74.8)

52.1

(46.4-57.5)

PFS by investigator

Median PFS (months) (95% CI)

40.7

(36.5-NC)

20.7

(17.3-23.5)

Hazard ratio (95% CI)

HR 0.49 (0.39-0.61)

Nominal p-value

p<0.00001ii

PFS2 by investigatoriii

Median PFS2 (months) (95% CI)

NC

(NC-NC)

36.5

(36.1-NC)

Hazard ratio (95% CI)

HR 0.60 (0.45-0.79)

Nominal p-value

0.00038ii

ORR by BICR iv

Confirmed ORR (%) (95% CI)v

85.1

(81.2-88.5)

78.6

(74.1-82.5)

CR % (n)

15.1 (58)

8.5 (33)

PR % (n)

70 (268)

70 (271)

SD % (n)

9.9 (38)

14.5 (56)

Median DOR in months (95% CI)

39.2

(35.1-NC)

26.4

(22.3-NC)

Remaining in response at 24 months (%)​

73.3​

54.9​

THP, taxane, trastuzumab and pertuzumab; PFS, progression-free survival; BICR, blinded independent central review, CI, confidence interval; NC, not calculable; HR, hazard ratio; ORR, objective response rate; CR, complete response; PR, partial response, SD, stable disease; DOR, duration of response

i. Interim analysis was based on a data cut-off of 26 Feb 2025; interim analysis criterion for superiority for primary endpoint (P-value <0.00043); ~38% maturity at data cut-off
ii. Stratified log-rank test
iii. PFS2 was defined by investigators according to local standard clinical practice as the time from randomisation to second progression (earliest progression event following first subsequent therapy) or death
iv. ORR is (CR + PR) based on RECIST v1.1
v. Response required confirmation after 4 weeks

Median duration of follow-up was nearly 2.5 years (29.2 months). As of the data cut-off, 302 (39.6%) patients remained on treatment, 174 in the Enhertu plus pertuzumab arm and 128 in the THP arm.

The safety profile of Enhertu in combination with pertuzumab in DESTINY-Breast09 was consistent with the known profiles of each individual therapy with no new safety concerns identified. Interstitial lung disease (ILD)/pneumonitis occurred in 12.1% of patients treated with Enhertu in combination with pertuzumab, as determined by an independent adjudication committee. The majority of ILD events were low Grade (Grade 1 [n=17; 4.5%] or Grade 2 [n=27; 7.1%]). There were no Grade 3 or Grade 4 ILD events. There were two Grade 5 (0.5%) ILD events in the Enhertu plus pertuzumab arm.

An additional investigational arm of the trial assessing Enhertu monotherapy versus THP remains blinded to patients and investigators and will continue to the final PFS analysis.

Enhertu is a specifically engineered HER2-directed DXd antibody drug conjugate (ADC) discovered by Daiichi Sankyo and being jointly developed and commercialised by Daiichi Sankyo and AstraZeneca.

Enhertu is already approved in more than 80 countries as 2nd-line treatment for patients with HER2-positive breast cancer based on the results from the DESTINY-Breast03 trial.

Notes

HER2-positive metastatic breast cancer
Breast cancer is the second most common cancer and one of the leading causes of cancer-related deaths worldwide.1 More than two million breast cancer cases were diagnosed in 2022, with more than 665,000 deaths globally.1 While survival rates are high for those diagnosed with early breast cancer, only about 30% of patients diagnosed with or who progress to metastatic disease are expected to live five years following diagnosis.2

HER2 is a tyrosine kinase receptor growth-promoting protein expressed on the surface of many types of tumours including breast cancer.3 HER2 protein overexpression may occur as a result of HER2 gene amplification.4

HER2-positive metastatic breast cancer is an aggressive disease driven by overexpression or amplification of HER2 that affects 15% to 20% of patients with metastatic breast cancer.5,6 Approximately 23,000 patients are treated each year in the 1st-line HER2-positive setting across G7 countries alone.7

While HER2-targeted therapies have improved outcomes, prognosis remains poor with most patients experiencing disease progression within two years of 1st-line treatment with THP, which has been the standard of care for more than a decade.4,8-10 Further, approximately one in three patients do not go on to receive treatment following 1st-line therapy due to disease progression or death.11,12

DESTINY-Breast09
DESTINY-Breast09 is a global, multicentre, randomised, open-label, Phase III trial evaluating the efficacy and safety of Enhertu (5.4 mg/kg) either alone or in combination with pertuzumab versus standard of care THP (a taxane [docetaxel or paclitaxel], trastuzumab and pertuzumab) as a 1st-line treatment in patients with HER2-positive metastatic breast cancer.

Patients were randomised 1:1:1 to receive either Enhertu monotherapy with a pertuzumab matching placebo; Enhertu in combination with pertuzumab; or THP. Randomisation was stratified by prior treatment (de novo metastatic disease versus progression from early-stage disease), hormone receptor status and PIK3CA mutation status.

The primary endpoint of DESTINY-Breast09 is PFS as assessed by BICR in both the Enhertu monotherapy and Enhertu combination arms. Secondary endpoints include OS, ORR, DOR, investigator-assessed PFS and PFS2 and safety.

DESTINY-Breast09 enrolled 1,157 patients across multiple sites in Africa, Asia, Europe, North America and South America. For more information about the trial, visit ClinicalTrials.gov.

Enhertu
Enhertu is a HER2-directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC Technology, Enhertu is the lead ADC in the oncology portfolio of Daiichi Sankyo and the most advanced programme in AstraZeneca’s ADC scientific platform. Enhertu consists of a HER2 monoclonal antibody attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers.

Enhertu (5.4mg/kg) is approved in more than 80 countries worldwide for the treatment of adult patients with unresectable or metastatic HER2-positive (immunohistochemistry [IHC 3+ or in-situ hybridisation [ISH]+) breast cancer who have received a (or one or more) prior anti-HER2-based regimen, either in the metastatic setting or in the neoadjuvant or adjuvant setting, and have developed disease recurrence during or within six months of completing therapy based on the results from the DESTINY-Breast03 trial.

Enhertu (5.4mg/kg) is approved in more than 80 countries worldwide for the treatment of adult patients with unresectable or metastatic HER2-low (IHC 1+ or IHC 2+/ ISH-) breast cancer who have received a prior systemic therapy in the metastatic setting or developed disease recurrence during or within six months of completing adjuvant chemotherapy based on the results from the DESTINY-Breast04 trial.

Enhertu (5.4mg/kg) is approved in more than 30 countries for the treatment of adult patients with unresectable or metastatic hormone receptor (HR)-positive, HER2-low (IHC 1+ or IHC 2+/ISH-) or HER2-ultralow (IHC 0 with membrane staining) breast cancer, as determined by a locally or regionally approved test, that have progressed on one or more endocrine therapies in the metastatic setting based on the results from the DESTINY-Breast06 trial.

Enhertu (5.4mg/kg) is approved in more than 60 countries worldwide for the treatment of adult patients with unresectable or metastatic non-small cell lung cancer (NSCLC) whose tumours have activating HER2 (ERBB2) mutations, as detected by a locally or regionally approved test, and who have received a prior systemic therapy based on the results from the DESTINY-Lung02 and/or DESTINY-Lung05 trials. Continued approval in China and the US for this indication is contingent upon verification and description of clinical benefit in a confirmatory trial.

Enhertu (6.4mg/kg) is approved in more than 70 countries worldwide for the treatment of adult patients with locally advanced or metastatic HER2-positive (IHC 3+ or 2+/ISH+) gastric or gastroesophageal junction (GEJ) adenocarcinoma who have received a prior trastuzumab-based regimen based on the results from the DESTINY-Gastric01, DESTINY-Gastric02 and/or DESTINY-Gastric06 trials. Continued approval in China for this indication will depend on whether a randomised controlled confirmatory clinical trial can demonstrate clinical benefit in this population.

Enhertu (5.4mg/kg) is approved in the US and other countries for the treatment of adult patients with unresectable or metastatic HER2-positive (IHC 3+) solid tumours who have received prior systemic treatment and have no satisfactory alternative treatment options based on the results from the DESTINY-PanTumor02, DESTINY-Lung01 and DESTINY-CRC02 trials. Continued approval for this indication in the US is contingent upon verification and description of clinical benefit in a confirmatory trial.

Enhertu clinical development programme
A comprehensive global clinical development programme is underway evaluating the efficacy and safety of Enhertu as monotherapy, in combination or sequentially with other anti-cancer therapies across multiple HER2-targetable cancers.

On June 2, 2025 Allarity Therapeutics, Inc. ("Allarity" or the "Company") (NASDAQ: ALLR), a Phase 2 clinical-stage pharmaceutical company dedicated to developing stenoparib—a differentiated, dual PARP and WNT pathway inhibitor—today announced that the first patient has been enrolled in its new Phase 2 clinical trial protocol of stenoparib for the treatment of advanced, platinum-resistant or platinum-ineligible ovarian cancer (Press release, Allarity Therapeutics, JUN 2, 2025, https://allarity.com/press-release/allarity-therapeutics-announces-first-patient-enrolled-in-new-phase-2-clinical-trial-protocol-of-stenoparib-in-advanced-ovarian-cancer/ [SID1234653633]).

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The newly launched protocol will accelerate the clinical development of stenoparib and its drug-specific Drug Response Predictor (DRP) companion diagnostic (CDx) toward potential FDA approval. It builds on encouraging data from Allarity’s earlier and still ongoing Phase 2 study, which demonstrated that patients on twice-daily stenoparib showed durable clinical benefit and that stenoparib was well tolerated. Two patients remain on treatment and continue to derive benefit after more than 20 months. Reflecting the compelling and durable clinical responses observed in platinum-resistant patients to date, the new trial protocol specifically focuses on evaluating stenoparib in patients with advanced, recurrent, platinum-resistant, or platinum-ineligible ovarian cancer—patients for whom current treatment options are extremely limited and typically involve additional chemotherapy, which is associated with well-documented side effects.

"With the enrollment of the first patient, we are fulfilling our promise to accelerate stenoparib’s clinical development as a potentially safer, more effective alternative to chemotherapy for women with advanced, recurrent ovarian cancer," said Thomas Jensen, Chief Executive Officer of Allarity Therapeutics. "This new protocol reflects critical input from leading gynecologic oncologists, and allows us to solidify the importance of DRP for patients who are most likely to receive clinical benefit from stenoparib. This study also allows us to confirm and extend our current findings that show clinical benefit from twice daily dosing."

In addition to assessing overall efficacy and safety, the new trial protocol is designed to further advance the Company’s understanding of stenoparib’s modulation of the WNT signaling pathway—a key driver of disease progression in ovarian and other cancers. The Company is actively pursuing ways to deepen its insights into the therapeutic importance of this WNT-modulating activity and how this, in addition to a cleaner safety profile, distinguishes stenoparib from first-generation PARP inhibitors.

Building on the clinical benefit of the current dosing schedule, this updated study design also includes an additional dosing level to explore the optimal dose for enhancing clinical benefit, aligning Allarity with the FDA’s Project Optimus initiative to inform the start of pivotal registration trials.

The trial is expected to generate significant clinical data by late summer 2026. Allarity plans to pursue multiple advantaged regulatory pathways to expedite potential approval of both stenoparib and its DRP companion diagnostic (CDx).

About Stenoparib
Stenoparib is an orally available, small-molecule dual-targeted inhibitor of PARP1/2 and tankyrase 1/2. At present, tankyrases are attracting significant attention as emerging therapeutic targets for cancer, principally due to their role in regulating the Wnt signaling pathway. Aberrant Wnt/β-catenin signaling has been implicated in the development and progression of numerous cancers. By inhibiting PARP and blocking Wnt pathway activation, stenoparib’s unique therapeutic action shows potential as a promising therapeutic for many cancer types, including ovarian cancer. Allarity has secured exclusive global rights for the development and commercialization of stenoparib, which was originally developed by Eisai Co. Ltd. and was formerly known under the names E7449 and 2X-121.

About the Drug Response Predictor – DRP Companion Diagnostic
Allarity uses its drug-specific DRP to select those patients who, by the gene expression signature of their cancer, may have a high likelihood of benefiting from a specific drug. By screening patients before treatment, and only treating those patients with a sufficiently high, drug-specific DRP score, the therapeutic benefit rate may be enhanced. The DRP method builds on the comparison of sensitive vs. resistant human cancer cell lines, including transcriptomic information from cell lines, combined with clinical tumor biology filters and prior clinical trial outcomes. DRP is based on messenger RNA expression profiles from patient biopsies. The DRP platform has shown an ability to provide a statistically significant prediction of the clinical outcome from drug treatment in cancer patients across dozens of clinical studies (both retrospective and prospective). The DRP platform, which may be useful in all cancer types and is patented for dozens of anti-cancer drugs, has been extensively published in the peer-reviewed literature.