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Director, Client Strategy, Clinical Trial Financial Management, Medidata

As stakeholders debate fair market value in clinical trial budgeting, a new task force works to align sponsors, CROs, and sites on transparency, sustainability, and efficiency.

Exploring Perspectives of Fair Market Value in Clinical Trial Budgeting

Video interview with Sepehr Shojaei, VP, Design Solutions, Lightship

Lightship's Approach to Accessible, Representative, and Impactful Clinical Trials

Lightship prioritizes patient accessibility and centricity in clinical trials, ensuring a seamless and positive experience for every participant. Learn more about:

Lightship's mission and core purpose as a company

How Lightship’s mobile nursing teams and home visits enhance study participation and retention

The role of mobile research units in the community and how they enhance participant education, accessibility, and convenience

Sepehr Shojaei, VP of Design Solutions at Lightship, talks about how the company works with pharma and contract research organization (CRO) partners to support clinical trials that are patient-first and accessible.

Latest Conference Coverage

Lightship’s Approach to Accessible, Representative, and Impactful Clinical Trials

Video interview with David MacMurchy, CEO of Lightship

Accelerate Inclusive Enrollment and Delivery with Lightship

Lightship focuses on patient accessibility and centricity in clinical trials, ensuring the patient experience is a positive one. Learn more about:

Lightship's impact on achieving diversity in clinical trials by engaging underrepresented patient populations

How Lightship utilizes hybrid and decentralized trial designs to reduce patient burden

The impact a patient centric model has on clinical trial participation and outcomes

David MacMurchy, Chief Executive Officer at Lightship, offers some insights into the company's mission toward improving equity and diversity in clinical trials. 

AstraZeneca and Daiichi Sankyo have shared positive data from the Phase III DESTINY-Breast09 clinical trial (NCT04784715) of Enhertu (fam-trastuzumab deruxtecan-nxki) plus pertuzumab as a first-line treatment for patients with HER2-positive metastatic breast cancer.

The Enhertu-pertuzumab combination demonstrated a statistically significant and clinically meaningful improvement in progression-free survival (PFS) compared to a taxane, trastuzumab, and pertuzumab (THP) regimen. Detailed data from the DESTINY-Breast09 study were shared at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting.

Robust PFS benefit observed across multiple patient subgroups

Results from a prespecified interim analysis showed that Enhertu and pertuzumab reduced the risk of disease progression or death by 44% versus THP. The Enhertu-pertuzumab combination achieved a median PFS of 40.7 months, compared to 6.9 months for THP. The PFS benefit for Enhertu and pertuzumab was consistent across multiple patient subgroups including de novo or recurrent disease, hormone receptor status, and PIK3CA mutation status.

In a press release, 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.”

High objective response rate and durable responses reported

The Enhertu-pertuzumab duo had a confirmed objective response rate (ORR) of 85.1% versus 78.6% for THP. There were 58 complete responses with Enhertu plus pertuzumab compared to 33 with THP. Enhertu plus pertuzumab demonstrated a median duration of response (DOR) of 39.2 months, while THP demonstrated 26.4 months.

According to AstraZeneca, overall survival (OS) data were not mature at the time of this analysis. However, the interim data show an early trend favoring the Enhertu-pertuzumab combination compared to THP.

Global trials and additional studies support Enhertu’s broad potential

The Phase III DESTINY-Breast09 trial is a global, multicenter, randomized, open-label study enrolling patients at multiple sites in Africa, Asia, Europe, North America, and South America. The study features arms for Enhertu as monotherapy, Enhertu plus pertuzumab, and THP. A total of 1,157 patients were randomized in a 1:1:1 ratio across the three arms.

The study’s primary endpoint is PFS, plus key secondary endpoints including investigator-assessed PFS, OS, ORR, duration of response, investigator-assessed time to second progression or death, patient-reported tolerability, pharmacokinetics, and safety.

AstraZeneca initially shared news of Enhertu plus pertuzumab demonstrating a significant improvement in PFS in patients with HER2-positive metastatic breast cancer earlier in April.

In a press release from the time, Susan Galbraith, executive vice president, oncology hematology R&D, AstraZeneca, said “This is the first trial in more than a decade to demonstrate superior efficacy across a broad HER2-positive metastatic breast cancer patient population compared to the current first-line standard of care. This is a significant milestone for patients and sets the foundation for Enhertu in combination with pertuzumab as an important treatment option in the first-line HER2-positive setting.”

Enhertu is also being evaluated in the Phase III DESTINY-Breast11 trial (NCT05113251) in patients with high-risk, locally advanced HER2-positive early-stage breast cancer. In May, AstraZeneca shared that Enhertu followed by standard HER2-targeted therapy demonstrated a significant improvement in pathologic complete response (pCR) rates compared to current standard-of-care chemotherapy.

DESTINY-Breast11 randomized 927 patients 1:1:1 to receive either eight cycles of Enhertu monotherapy, four cycles of Enhertu and then four cycles of THP, or four cycles of dose-dense doxorubicin and cyclophosphamide followed by four cycles of THP. The trial’s primary endpoint is pCR, plus secondary endpoints including event-free survival, invasive disease-free survival, OS, and safety.

1. ENHERTU® (fam-trastuzumab deruxtecan-nxki) plus pertuzumab reduced the risk of disease progression or death by 44% vs. THP as 1st-line therapy in patients with HER2-positive metastatic breast cancer in DESTINY-Breast09 Phase III trial. News release. AstraZeneca. June 2, 2025. Accessed June 2, 2025. 

https://www.businesswire.com/news/home/20250602557687/en/ENHERTU-fam-trastuzumab-deruxtecan-nxki-plus-pertuzumab-reduced-the-risk-of-disease-progression-or-death-by-44-vs.-THP-as-1st-line-therapy-in-patients-with-HER2-positive-metastatic-breast-cancer-in-DESTINY-Breast09-Phase-III-trial

2. DESTINY-Breast09 Trial Shows Enhertu Plus Perjeta Significantly Improves Survival in HER2-Positive Metastatic Breast Cancer. 

. April 21, 2025. Accessed June 2, 2025. 

https://www.appliedclinicaltrialsonline.com/view/enhertu-perjeta-survival-her2-metastatic-breast-cancer

3. DESTINY-Breast11 Trial Shows Enhertu Plus THP Significantly Improves Response Rates in High-Risk HER2-Positive Early Breast Cancer. 

https://www.appliedclinicaltrialsonline.com/view/destiny-breast11-enhertu-her2-positive-early-breast-cancer

In the DESTINY-Breast09 study, Enhertu (fam-trastuzumab deruxtecan-nxki) plus pertuzumab reduced the risk of disease progression or death by 44% in patients with HER2-positive metastatic breast cancer.

AstraZeneca and Daiichi Sankyo Share Positive Data From Phase III DESTINY-Breast09 Trial of Enhertu Plus Pertuzumab

A primary analysis of the Phase III BREAKWATER trial (NCT0460742) show that a Braftovi (encorafenib)-based regimen delivered the first statistically significant and clinically meaningful overall survival (OS) benefit ever reported in the first-line setting for patients with 

-mutant metastatic colorectal cancer (mCRC).

BREAKWATER Trial Delivers First Survival Benefit in First-Line BRAF V600E Mutant Metastatic Colorectal Cancer

Results from the trial, presented at the 2025 ASCO Annual Meeting and published in 

), show the combination of Braftovi plus Erbitux (cetuximab) and mFOLFOX6 (fluorouracil, leucovorin, and oxaliplatin) may offer a potential new standard-of-care for the hard-to-treat mCRC subset, which is associated with a poor prognosis and limited responsiveness to traditional therapies.

“Patients with metastatic colorectal cancer whose tumors harbor a 

 mutation generally face a daunting prognosis, as this aggressive tumor often does not respond well to standard-of-care chemotherapy,” BREAKWATER co-principal investigator Elena Élez, MD, PhD, senior investigator at Vall d’Hebron Institute of Oncology in Barcelona, Spain, said in a press release. “The BREAKWATER results are the first promising survival outcomes ever reported for 

-mutant metastatic colorectal cancer in the first-line setting, representing a practice-changing breakthrough for patients.”

Overall and Progression-Free Survival Significantly Extended With Braftovi Combination

Braftovi, an oral small molecule kinase inhibitor, was granted accelerated approval by the FDA in December 2024 in combination with Erbitux and mFOLFOX6 for patients with mCRC with a 

 mutation, as detected by an FDA-approved test. The regulatory action, based on results from the BREAKWATER trial, marked the first and only targeted therapy combination approved as early as the first line of treatment for this patient population.

“Encorafenib is a highly selective, ATP-competitive, small-molecule BRAF inhibitor with antiproliferative and apoptotic activity in tumor cells expressing 

 mutations and has longer pharmacodynamic activity than other approved BRAF inhibitors,” the study authors wrote in 

. “In colorectal cancer, BRAF inhibition alone can cause the BRAF pathway to be reactivated by epidermal growth factor receptor (EGFR) owing to feedback loops within the signaling network (also known as rapid pathway feedback reactivation), which attenuates the activity of BRAF inhibitors. The value of targeting BRAF simultaneously with EGFR inhibition to overcome reactivation has been shown previously.”

The randomized, active-controlled, open-label, multicenter BREAKWATER trial analyzed Braftovi with Erbitux, either alone or combined with mFOLFOX6, in previously untreated patients with 

Patients were randomly assigned to receive either Braftovi 300 mg administered orally once daily with Erbitux (discontinued after 158 patients were randomly assigned), Braftovi 300 mg administered orally once daily with Erbitux and mFOLFOX6 (n=236), or a control cohort who received mFOLFOX6, FOLFOXIRI, or CAPOX, with or without bevacizumab (n=243).

The trial’s dual primary endpoints are objective response rate (ORR) and progression-free survival (PFS) as assessed by blinded independent central review (BICR), with OS being a key secondary endpoint.

Objective Response Rate and Duration of Response Reinforce Clinical Value

These latest data show the Braftovi combination regimen lowered the risk of death by 51% compared to standard-of-care chemotherapy with or without bevacizumab (Hazard Ratio [HR] 0.49; 95% Confidence Interval [CI], 0.38, 0.63, p<0.0001). 

Patients administered the Braftovi combination had a median OS of 30.3 months (95% CI, 21.7, Not Estimated) compared to 15.1 months among patients administered chemotherapy with or without bevacizumab (95% CI, 13.7, 17.7).

For the PFS endpoint, the Braftovi combination lowered the risk of disease progression or death by 47% versus standard-of-care chemotherapy with or without bevacizumab (HR 0.53; 95% CI, 0.41, 0.68, p<0.0001) as assessed by BICR. 

Patients administered the Braftovi combination had a median PFS of 12.8 months (95% CI, 11.2, 15.9) compared to 7.1 months (95% CI, 6.8, 8.5) in the chemotherapy cohort.

“The early separation of the Kaplan–Meier curves for progression-free survival indicated an early clinical benefit in the [Braftovi plus Erbitux and mFOLFOX6] group as compared with the standard-care group,” the study authors wrote in 

. “The median overall survival was more than twice as long in the [Braftovi plus Erbitux and mFOLFOX6] group as in the standard-care group, with early separation of the Kaplan–Meier curves. The survival advantage that had been observed at the previous interim analysis was sustained, which supports the significant survival benefit in the [Braftovi plus Erbitux and mFOLFOX6] group.”

 show patients administered Braftovi 300 mg with Erbitux and mFOLFOX6 had an ORR of 61% compared to 40% in the chemotherapy with or without bevacizumab cohort. Estimated median duration of response (DoR) in the Braftovi with Erbitux and mFOLFOX6 cohort was 13.9 months compared to 11.1 months in the chemotherapy cohort, with or without bevacizumab.

Regulatory Context and Potential for Full FDA Approval in 2025

Updated data for ORR as per BICR confirmed the prior advantage for the Braftovi combination compared to chemotherapy with or without bevacizumab (65.7%; 95% CI, 59.4, 71.4 and 37.4%; 95% CI, 31.6, 43.7, respectively), while estimated median DoR and median time to response stayed consistent with the previously released results.

-mutant metastatic colorectal cancer is more than double compared to those with no known mutation,” Michael Sapienza, CEO, Colorectal Cancer Alliance, said in the release. “These survival outcomes from the BREAKWATER study bring renewed hope to patients and their loved ones, providing the possibility of more time together. We are thrilled to see important cancer research propel us closer to our goal of ending this disease.”

1. Pfizer’s BRAFTOVI® Combination Regimen Cuts the Risk of Death in Half for Patients with BRAF V600E-Mutant Metastatic Colorectal Cancer. News release. Pfizer. May 30, 2025. Accessed June 3, 2025. 

https://www.pfizer.com/news/press-release/press-release-detail/pfizers-braftovir-combination-regimen-cuts-risk-death-half

2. A Study of Encorafenib Plus Cetuximab With or Without Chemotherapy in People With Previously Untreated Metastatic Colorectal Cancer. ClinicalTrials.gov. Updated December 17, 2024. Accessed June 3, 2025. 

https://clinicaltrials.gov/study/NCT04607421

3. Elez E., et al. Encorafenib, Cetuximab, and mFOLFOX6 in BRAF-Mutated Colorectal Cancer. 

4. U.S. FDA Approves Pfizer’s BRAFTOVI® Combination Regimen as First-Line Treatment of BRAF V600E-Mutant Metastatic Colorectal Cancer. News release. Pfizer. December 20, 2024. Accessed June 3, 2025. 

https://www.businesswire.com/news/home/20241210321033/en/U.S.-FDA-Approves-Pfizer%E2%80%99s-BRAFTOVI%C2%AE-Combination-Regimen-as-First-Line-Treatment-of-BRAF-V600E-Mutant-Metastatic-Colorectal-Cancer

5. Pfizer’s BRAFTOVI® Combination Regimen Significantly Improved Progression-Free Survival and Overall Survival in Phase 3 BREAKWATER Trial. News release. Pfizer. February 3, 2025. Accessed June 3, 2025. 

https://www.pfizer.com/news/press-release/press-release-detail/pfizers-braftovir-combination-regimen-significantly

Phase III data presented at ASCO 2025 and published in The New England Journal of Medicine show that Pfizer’s Braftovi (encorafenib), combined with Erbitux (cetuximab) and mFOLFOX6, significantly improves overall survival and progression-free survival in treatment-naïve patients with BRAF V600E-mutant metastatic colorectal cancer—potentially establishing a new first-line standard-of-care for this high-risk population.

Phase III BREAKWATER Trial Shows Braftovi-Based Regimen Improves Survival in BRAF V600E-Mutant Metastatic Colorectal Cancer

In this video interview, Michel van Harten, MD, CEO, myTomorrows, discusses where the clinical research industry currently stands with AI adoption. 

Bridging Innovation and Trust with Artificial Intelligence

, Michel van Harten, MD, CEO, myTomorrows, discussed the integration of artificial intelligence (AI) in clinical trials, highlighting its potential to reduce costs, accelerate timelines, and improve inclusion. Looking forward, advancements with AI are expected to speed up drug discovery, predict drug efficacy, and develop digital twins for personalized treatment simulations, potentially reducing trial risks and costs.

ACT: Where do you think the clinical trials industry currently stands with AI integration?

I think in general, there's a lot of optimism, especially on the industry side. Sponsors and also CROs (contract research organizations) are recognizing the potential of AI to reduce costs, accelerate timelines, and also improve inclusion. I think, for example, AI is already being actively used to design trials and protocols to identify trial sites with access to specific populations, and also to match eligible patients faster and enroll them faster.

On the healthcare provider side, besides early adopters, there's sometimes hesitancy. In general, in healthcare, you must be very careful with introducing technology. I think first, the quality of the data is everything. For example, for us, we work with sensitive patient and clinical data, and although we do not advise physicians and patients, we do give them the options, the pre-approval treatment options, so clinical trials, that are out there and they need to be correct, so our AI models are as good as the data we feed them. We invest also heavily in cleaning and validating the data before the AI part can even begin.

Then second, I think transparency and explainability is important, and they're crucial in building trust. In healthcare, patients and providers have to understand how decisions are made, so we always show them the reasoning in a very detailed way. In addition, we provide them the option to correct the AI if they disagree, so the physician or the patient is always in the driver's seat. Until the AI is perfect, you have to build in checks and balances and develop, together with those physicians and key opinion leaders to remove skepticism early on.

In this video interview, Krinx Kong, chief commercial officer, Cognivia, discusses how trial design and timelines could be impacted by a potential mandate for placebo use across all vaccine trials.

How Vaccine Trials Could be Affected by Potential Policy Changes

, Krinx Kong, chief commercial officer, Cognivia, discussed the potential impacts of policy shifts on vaccine trial design and patient perceptions. Stricter regulations could increase trial complexity, affecting recruitment and retention. Kong emphasized behavioral insights as crucial to understanding patient motivation and mitigating dropouts. Looking forward with the potential for policy changes in vaccine trials, clinical operations professionals must focus on flexibility, behavioral visibility, and effective communication to ensure success.

ACT: US Health and Human Services Secretary Robert F. Kennedy Jr. recently 

 on supporting placebo-controlled trials for all new vaccines. How could a potential policy shift in this area affect trial design and timelines?

First, it's important to clarify that placebo-controlled trials are already the gold standard in vaccine development, and are required by both the FDA and EMA when no approved alternatives exist. Therefore, the notion that these aren't already in use is misleading, or at least lacks context. Now, if a policy shift were to mandate placebo use in all vaccine trials, even where active comparators might be more appropriate, we'd likely see significant impacts on both design complexity and timelines. First, ethics boards may push back. If an effective vaccine already exists, withholding it in favor of placebo could be viewed as unethical. This leads to delays, extra review cycles, and potential public concern. Next, placebo-controlled designs often require longer follow ups, which can prolong timelines by months or even years. Lastly, these designs are frequently more difficult to recruit for, patients and parents may be reluctant to participate if there's a genuine chance of receiving no active protection. If policy does shift, having tools that can adapt trial design without compromising data integrity or patient trust will be essential.

Tina Mincher

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