Dato dxd for breast cancer and lung cancer: When is approval coming?

After launching Enhertu (fam-trastuzumab deruxtecan-nxki) in 2019, Daiichi Sankyo and AstraZeneca are now partnering again in a push for the approval of datopotamab deruxtecan (Dato-DXd). Similarly to Enhertu, dato dxd is initially intended for patients with advanced HER2-low and HER2-negative breast cancer. However, it seems to have more potential applications than that.

Both FDA and EMA approvals are pending for dato dxd in breast cancer and lung cancer. Here's what you need to know about approval timelines. Including all your options for accessing the treatment in the meantime.

How does Dato-DXd work for breast cancer and lung cancer?

Datopotamab deruxtecan (Dato-DXd) is a specialized cancer treatment known as an antibody-drug conjugate. It targets TROP2, a protein found on many cancer cells. It works by attaching to these cells and delivering a powerful anti-cancer medicine (deruxtecan) directly inside them. This targeted approach allows Dato-DXd to effectively kill cancer cells while causing less harm to healthy cells. This could potentially lead to fewer side effects compared to traditional chemotherapy.

How effective is Dato-DXd in clinical trials?

Based on the clinical trial results available so far, below is what we know about datopotamab deruxtecan's efficacy in treating breast cancer and lung cancer.

Datopotamab deruxtecan in breast cancer: Clinical trial results

Dato dxd's application for FDA and EMA approval has been based on the results of the Phase 3 TROPION-Breast01 trial ¹. The trial focused on patients with HR-positive, HER2-low or negative breast cancer, who had previously been treated with endocrine-based therapy and at least one systemic therapy.

Here are the key reportings from the trial:

• Datopotamab deruxtecan reduced the risk of disease progression or death by 37% compared to chemotherapy alone;
• Median progression-free survival was 6.9 months in patients treated with dato dxd, compared to 4.9 months with chemotherapy;
• 36.4% of patients treated with dato dxd responnded partially or completely to the treatment. 22.9% of patients treated only with chemotherapy had this response;
• At the time of interim results reporting, overall survival data had not reached statistical significance. However, the available data numerically favoured datopotamab deruxtecan over chemotherapy ¹.

In addition to this trial, these additional trials are also ongoing:

• TROPION-Breast02 and TROPION-Breast03, with a focus on patients with triple-negative breast cancer;
• TROPION-Breast04, focusing on dato dxd in combination with durvalumab as neoadjuvant treatment for early-stage triple negative and HR low, HER2 low or negative breast cancers ²;
• TROPION-Breast05, focusing on patients with advanced or metastatic triple negative breast cancer whose tumors express PD-L1 ².

Datopotamab deruxtecan in NSCLC: Clinical trial results

Dato dxd's applicattion for FDA and EMA approval was supported by the results from the phase 3 TROPION-Lung01 trial. The trial focused on dato dxd versus docetaxel for the treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC) after at least one prior line of therapy ³.

The key reported results were:

• Dato dxd significantly improved progression-free survival;
• 26.4% of patients treated with dato dxd responded partially or completely to the treatment. In comparison, 12.8% of the docetaxel patients had the same response;
• Patients with non-squamous NSCLC seemed to benefit the most from the treatment ⁴.

Additional ongoing clinical trials focusing on dato dxd in lung cancer include:

• TROPION-Lung02, which studies dato dxd in combination with pembrolizumab in patients with advanced or metastatic NSCLC;
• TROPION-Lung04, which combines dato dxd with immunotherapy (and chemotherapy) in patients with advanced or metastatic non-small cell lung cancer;
• TROPION-Lung05, which focuses on advanced or metastatic NSCLC with genomic alterations;
• TROPION-Lung07, which focuses on datopotamab deruxtecan with pembrolizumab in 1L NSCLC;
• TROPION-Lung08, focusing on dato dxd with pembrolizumab as a first-line treatment for NSCLC.

Is Dato-DXd approved somewhere?

Not as of June 2024. Its applications for FDA and EMA approval are currently under review, for both breast cancer and lung cancer.

When will Dato-DXd get EMA approval?

Datopotamab deruxtecan has been officially under review by the EMA since 29th February 2024. Typically, the review process takes up to 210 days, unless any pauses are needed to request additional data. Assuming the best-case scenario, dato dxd's EMA approval could be a fact before the end of 2024.

When will dato dxd be available in Europe?

Getting EMA approval and becoming available across Europe aren't the same thing. After EMA approval, it takes each member state a different amount of time to negotiate local prices, reimbursements, and launch a new medicine on the local market. Germany's launch process tends to be the fastest, with an average of 100 days for oncological drugs. At the other end of the spectrum is Romania, where it can take up to 964 days on average for a new cancer medicine to become available.

This means that depending on where in Europe you're based, dato dxd could be available to you as early as mid-2025, or as late as 2028 ⁵.

When will datopotamab deruxtecan be approved in the UK?

That's more difficult to say. As of June 2024, there is no marketing authorization application submitted to the MHRA for dato dxd.

However, this doesn't have to mean it will take longer for dato dxd to get MHRA approval. According to post-Brexit regulations, the MHRA can approve medicines locally as soon as they get the green light from another trusted regulatory body (such as the EMA or FDA). This is known as the International Reliance Procedure ⁶. It wouldn't be surprising if the MHRA decides to take this road for approving dato dxd.

When will dato dxd be available in the UK?

If the MHRA approves datopotamab deruxtecan simultaneously with the EMA, expected towards the end of 2024, the medicine will then require a NICE assessment before becoming available to patients in the UK. NICE will decide whether to make it available on the NHS. If approved, the medicine should be available to UK patients within three months of the decision date.

Assuming a best-case scenario, where the MHRA follows a potential EMA approval in late 2024, and NICE makes a positive decision soon after, dato dxd could be available in the UK by mid-2025. Only time will tell if such a timeline is indeed realistic.

How to get dato dxd before it's available in your country

Despite what the timelines above suggest, waiting is not the only option for patients with HER-negative breast cancer or advanced NSCLC in Europe, the UK, or anywhere else.

As soon as dato dxd gets an approval somewhere, you can immediately access the medicine anywhere else by importing it for your personal use. This option is known as Named Patient Import, or expanded access. Here's how it works.

Datopotamab deruxtecan expanded access

Even if a medicine is not yet approved or available in your country, you can legally access it. A regulation known as Named Patient Import allows you to buy and import a medicine, as long as it meets these conditions:

• it is approved somewhere;
• it is not approved or available in your country (yet);
• it has no local alternatives, and
• it is for personal use.

This process requires a prescription from your treating doctor. As in all other cases, the doctor assumes responsibility for the treatment. Per country, specific documentation requirements can vary.

Do you want to start your treatment with dato dxd as soon as possible, using the Named Patient Import regulation? You will first need to consult your treating doctor and get a suitable prescription.

Already have a prescription? Share it with our team at Everyone.org. We can support you with buying dato dxd as soon as it's approved somewhere in the world.

References:

1.  Datopotamab deruxtecan significantly extended progression-free survival vs. chemotherapy in patients with HR-positive, HER2-low or negative breast cancer in TROPION-Breast01 Phase III trial. AstraZeneca, 23 October 2023.
2. Press Release - Two Phase 3 Trials of Datopotamab Deruxtecan Plus Durvalumab Initiated in Patients Across Two Breast Cancer Subtypes. Daiichi Sankyo, 18 December 2023.
3. Datopotamab deruxtecan showed clinically meaningful overall survival improvement vs. chemotherapy in patients with advanced nonsquamous non-small cell lung cancer in TROPION-Lung01 Phase III trial. AstraZeneca, 27 May 2024.
4. Dato-DXd vs Docetaxel in Previously Treated Advanced/Metastatic Non–Small Cell Lung Cancer: Results of the Randomized Phase III Study TROPION-Lung01. OncLive, 31 October 2023.
5. EFPIA Patients W.A.I.T. Indicator 2021 Survey. IQVIA, Accessed 10 June 2024.
6. Fast-Tracking Approval of Medicines - UK Publishes Detailed Guidance on its New International Recognition Procedure. Inside EU Life Sciences, 11 September 2023.