Clinical Trial Eligibility: How Biomarkers and Inclusion Criteria Shape Cancer Treatment

By Lindsey Smith On 16 Dec, 2025 Comments (8)

When you hear about a new cancer drug in the news, it’s easy to assume it’s available to anyone with that type of cancer. But that’s not how it works. Before a single patient can even start a clinical trial, they must pass through a strict filter called clinical trial eligibility. And today, that filter is increasingly defined by something called biomarkers-measurable signs in your body that tell doctors whether a drug is likely to work for you.

What Are Biomarkers, Really?

A biomarker isn’t just a lab result. It’s a biological signal-something you can measure-that tells a story about your cancer. It could be a gene mutation, a protein level in your blood, or even a specific pattern on a scan. The FDA defines biomarkers as objective measures that show how your body is responding to disease or treatment. They’re not guesses. They’re facts.

In cancer care, biomarkers are now the gatekeepers of treatment. Think of them like a key. If your tumor has the right key-say, a BRCA1 mutation or an EGFR gene change-then a specific drug might unlock its effect. If you don’t have that key, the drug won’t work, no matter how advanced it is.

Around 60% of cancer drugs approved between 2017 and 2022 required biomarker testing before use. That’s not a small trend. It’s the new standard. For example, in non-small cell lung cancer, if you don’t test for ALK or ROS1 mutations, you’re not even considered for certain targeted therapies. It’s not optional anymore-it’s essential.

Why Biomarkers Changed Everything

Before biomarkers, clinical trials were like throwing a net into the ocean. You’d enroll hundreds of patients with the same cancer type, hoping some would respond. But cancer isn’t one disease-it’s hundreds. Two people with “breast cancer” can have tumors that behave completely differently.

That’s why old trials failed so often. More than 60% of Phase 2 cancer trials didn’t work-not because the drug was bad, but because it was given to people who couldn’t possibly benefit. Biomarker-driven trials flipped that script.

Now, trials look for patients whose tumors have specific markers. The result? Success rates jumped. In trials using biomarkers, nearly 50% of Phase 2 studies led to approval. In trials without them, it was closer to 27%. That’s an 84% increase in success.

Take HER2-positive breast cancer. Before HER2 testing, only about 12% of patients responded to certain drugs. Once doctors started using HER2 as an eligibility criterion, response rates jumped to 32%. That’s not a small improvement-it’s life-changing.

Types of Biomarkers That Matter

Not all biomarkers are the same. The FDA breaks them into seven categories, but in cancer trials, four matter most:

Predictive biomarkers: These tell you if a drug will work. Like HER2 for trastuzumab, or PD-L1 for immunotherapy.
Prognostic biomarkers: These tell you how aggressive your cancer is, regardless of treatment. Like TP53 mutations in some leukemias.
Diagnostic biomarkers: These confirm the cancer type. Like BRAF V600E in melanoma.
Pharmacodynamic biomarkers: These show if the drug is hitting its target. Like a drop in circulating tumor DNA after treatment.

When you’re screened for a trial, the team isn’t just checking your age or stage. They’re running a molecular profile. A single blood draw or tissue biopsy can reveal dozens of these markers at once.

Split scene: biopsy on one side, liquid biopsy with glowing DNA on the other, medical graphs in background.

How Inclusion Criteria Work With Biomarkers

Inclusion criteria are the rules that decide who can join a trial. They used to be simple: “Must have Stage III lung cancer.” Now, they’re layered:

Diagnosis: Non-small cell lung cancer
Stage: Metastatic (Stage IV)
Performance status: ECOG 0-1 (meaning you’re able to carry out light activity)
Biomarker: EGFR exon 19 deletion or L858R mutation confirmed by NGS testing
Previous treatment: No prior EGFR-targeted therapy

That last bullet is the game-changer. If your tumor doesn’t have the exact mutation the drug targets, you’re automatically excluded-even if you’re otherwise perfect for the trial.

This sounds strict, but it’s designed to protect you. Joining a trial that won’t help you means exposure to side effects, time away from work, and emotional toll-all without benefit. Biomarkers make sure you’re only in trials that have a real chance of working for you.

The Hidden Challenges

Biomarkers sound perfect, but they’re not simple to use. Many patients don’t even get tested because:

Testing takes time-often 7 to 14 days for complex genomic panels.
Not every hospital has the right lab. Some require sending samples to distant centers.
Insurance doesn’t always cover the full cost of testing.
Some biomarkers are rare. For example, NTRK fusions occur in less than 1% of solid tumors. Finding even one patient can take months.

Global trials face another issue: biomarker rates vary by region. The HLA-A*02:01 marker, used in some cell therapies, appears in over 50% of Europeans but under 20% in parts of North America. That means a trial might work well in Germany but fail to recruit enough patients in Canada.

Sites that succeed in biomarker trials have invested heavily: CLIA-certified labs, trained staff, standardized sample kits, and real-time tracking systems. But 76% of research coordinators say their teams still lack proper training on biomarker collection. One wrong blood tube, one delayed shipment, and your sample is ruined.

Patients at a genomic crossroads, guided by a DNA key, in a surreal landscape of genes and hospitals.

What’s Next? The Future Is Multi-Omic

The next wave isn’t single biomarkers-it’s panels. Think of it like a fingerprint, not a key. Instead of checking one gene, labs now analyze hundreds of genes, proteins, and even immune cells at once. This is called multi-omic profiling.

By 2025, 65% of new trials are expected to use these combined biomarker panels. AI is helping too. Companies are using machine learning to find hidden patterns in data that humans would miss-like a combination of three genes that together predict response, even if each one alone doesn’t.

Liquid biopsies are another breakthrough. Instead of a tissue biopsy (which can be invasive and risky), doctors can now use a simple blood draw to detect tumor DNA floating in the bloodstream. This allows for faster testing, repeated monitoring, and even detection of resistance mutations before the tumor grows.

What This Means for You

If you or someone you know is considering a cancer clinical trial, here’s what you need to do:

Ask for comprehensive biomarker testing-don’t assume it’s automatic.
Find out which lab will do the testing and how long it takes.
Confirm whether insurance covers the full cost. If not, ask if the trial sponsor provides it.
Request a copy of the results. You have the right to them.
Ask: “Which biomarkers are required for this trial? What happens if I don’t have them?”

Don’t be discouraged if you don’t qualify for one trial. With biomarkers, there are dozens of trials targeting different mutations. Just because you’re not eligible for one doesn’t mean you’re not eligible for another.

Final Thought: Precision Isn’t Perfect-But It’s Progress

Biomarker-driven eligibility isn’t flawless. It’s expensive. It’s complex. It’s not equally accessible everywhere. But it’s the best tool we have to make sure the right patient gets the right drug at the right time.

The old way of treating cancer-guessing based on where the tumor is-was like using a sledgehammer. Now, we’re using a scalpel. It’s more precise. It’s more effective. And for patients, that means more hope, fewer side effects, and better outcomes.

The future of cancer care isn’t just about finding new drugs. It’s about matching the right drug to the right person-and biomarkers are how we’re doing it.

Do I need a biopsy to test for biomarkers?

Not always. While tissue biopsies are still common, liquid biopsies-blood tests that detect tumor DNA-are now used in over 30% of Phase 2+ cancer trials. They’re less invasive, faster, and can be repeated over time. But if your tumor is hard to reach or the blood test is inconclusive, a tissue biopsy may still be required.

What if my biomarker test comes back negative?

A negative result doesn’t mean no options. Many trials now look for patients without certain mutations, especially for combination therapies or immunotherapies. You might also qualify for trials testing new biomarkers still in development. Always ask your oncologist about alternative trials, including those using broader screening or emerging markers.

Can I get biomarker testing done before I’m ready for a trial?

Yes. Many hospitals now offer proactive molecular profiling for cancer patients, even before they’re considering a trial. This is often called “precision oncology testing.” Having results ready can speed up your enrollment if you decide to join a trial later. Ask your oncology team if this is available at your center.

Are biomarker tests covered by insurance?

Most major insurers in the U.S. and U.K. cover FDA-approved biomarker tests for cancer, especially if they’re linked to an approved therapy. However, off-label or experimental tests may not be covered. Always check with your insurer and ask the trial coordinator if the sponsor will cover testing costs if insurance denies it.

Why do some trials require specific biomarkers while others don’t?

It depends on the drug’s mechanism. Targeted therapies-drugs designed to hit a specific mutation-require biomarkers to work. Immunotherapies may use PD-L1 as a guide, but can still help some patients without it. Early-phase trials often test multiple biomarkers to discover which ones predict response. Later-phase trials focus only on the strongest predictors to increase success rates.