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

When you hear about a new cancer drug in the news, it’s easy to assume it’s available to everyone. But the truth is, only a fraction of patients qualify to even try it. That’s because modern cancer clinical trials don’t just look at your diagnosis-they look at your biology. Biomarkers are now the gatekeepers of who gets in-and who doesn’t. And understanding how they work can change everything for patients and families navigating treatment options.

What Are Biomarkers, Really?

Biomarkers aren’t magic. They’re measurable signs in your body that tell doctors something about your cancer. They could be a gene mutation, a protein level in your blood, or even a specific pattern on a tumor scan. The FDA defines them as objective indicators of normal biology, disease, or how your body responds to treatment. In cancer trials, they’re used to find the right patients for the right drugs.

Think of it like a key and a lock. A drug is designed to fit one specific lock-a mutation in the EGFR gene, for example. If you don’t have that lock, the key won’t turn. That’s why testing for biomarkers isn’t optional anymore. Nearly 60% of cancer drugs approved between 2017 and 2022 required a biomarker test before use. Without it, you’re not even considered for the trial.

The Shift from ‘One Size Fits All’ to Precision Matching

Ten years ago, cancer trials enrolled patients based mostly on where the tumor was located-lung, breast, colon-and how advanced it was. Today, that’s outdated. A patient with lung cancer might be eligible for a trial meant for a different type of cancer if they share the same biomarker. That’s the power of precision medicine.

This change didn’t happen by accident. Trials using biomarker selection have nearly double the success rate in Phase 2 compared to traditional ones. Where older trials failed over 60% of the time because the drug just didn’t work on most patients, biomarker-driven trials now succeed nearly 50% of the time. Why? Because they’re testing the drug on people whose tumors actually have the target.

Take HER2 mutations in breast cancer. Before biomarker screening, only about 12% of patients responded to certain drugs. After selecting only those with the HER2 mutation, response rates jumped to 32%. That’s not just a number-it’s more time, more hope, more lives saved.

Types of Biomarkers Used in Cancer Trials

Not all biomarkers are the same. The FDA breaks them into seven types, but in cancer trials, you’ll mostly see four:

• Predictive biomarkers: Tell you if a drug will work for you. Examples: BRCA1/2 mutations for PARP inhibitors, PD-L1 levels for immunotherapy.
• Prognostic biomarkers: Show how aggressive your cancer is, regardless of treatment. Example: TP53 mutations often mean faster progression.
• Diagnostic biomarkers: Help confirm the cancer type. Example: ALK rearrangements in non-small cell lung cancer.
• Pharmacodynamic biomarkers: Show if the drug is hitting its target. Example: Drop in a specific protein after treatment.

Knowing which type you’re dealing with helps you understand why you were-or weren’t-accepted into a trial. It’s not always about whether the drug works. Sometimes it’s about whether your cancer has the right signature for it to even be tested on you.

How Inclusion Criteria Are Built Around Biomarkers

Inclusion criteria are the rules that say who can join a trial. Biomarkers have rewritten these rules. Instead of saying “patients with stage IV lung cancer,” now it might say: “patients with stage IV non-small cell lung cancer and an EGFR exon 19 deletion confirmed by NGS testing.”

That specificity comes with a cost. More tests. More time. More complexity. Sites need CLIA-certified labs. Samples must be handled just right-wrong blood tubes or delays in shipping can ruin results. One study found that 68% of sites face 7-14 day delays for specialized biomarker tests. That’s weeks lost while a patient’s condition may be worsening.

And it’s not just about having the test. The test must be validated. The FDA requires a Context of Use statement that answers: What’s the biomarker? How is it measured? What evidence supports it? Without this, even a perfectly identified mutation might not qualify you.

Why Some Patients Still Can’t Get In

Even with all the advances, many patients still get turned away-not because their cancer is too advanced, but because their biomarker profile doesn’t match. This isn’t a flaw in the system-it’s a feature. But it creates real problems.

Geographic disparities are huge. For example, the HLA-A*02:01 biomarker, used in some cell therapies, appears in 50% of Europeans but only 17% of North Americans. That means a trial in Germany might enroll quickly, while one in Atlanta struggles to find enough eligible patients. Global trials now have to plan for these differences-or risk failing before they start.

Another issue: not all sites can do the testing. A small community hospital might not have the equipment or expertise to run next-generation sequencing (NGS) panels. That means patients have to travel farther, wait longer, or miss out entirely. Sites with established biomarker infrastructure enroll patients 28 days faster than those without.

What’s Changing Now-and What’s Coming

The field is moving fast. Liquid biopsies-blood tests that detect tumor DNA-are now used in 31% of Phase 2+ cancer trials, up from just 9% in 2020. That means less invasive testing, faster results, and the ability to monitor changes over time. Some trials are even using dynamic eligibility: if your biomarker changes after starting treatment, you might be switched to a different drug mid-trial.

AI is helping too. Top pharmaceutical companies now use machine learning to find new biomarker patterns in huge datasets, speeding up discovery. By 2025, over two-thirds of new trials are expected to use multi-omic panels-combining DNA, RNA, protein, and metabolic data-to get a fuller picture.

The big shift? From biomarkers as a tool, to biomarkers as the standard. In 2022, 92% of new cancer drug approvals came with a biomarker-restricted label. That means if you don’t have the biomarker, you won’t get the drug-even after approval. This isn’t the future. It’s today.

What Patients Need to Know

If you’re considering a clinical trial, ask these questions early:

• What biomarker tests are required?
• Where will the test be done? Will I need to travel?
• How long will results take?
• What happens if the test is negative?
• Is there a backup trial if I don’t qualify?

Don’t assume your oncologist knows every trial’s requirements. Biomarker rules change monthly. Ask for a referral to a trial navigator or a specialized cancer center. Many large hospitals now have dedicated teams just for this.

Also, know your rights. If a trial requires a test you can’t access locally, you can often request that the sponsor cover the cost and send your sample to a central lab. It’s not guaranteed, but it’s worth asking.

The Bottom Line

Biomarkers have turned clinical trials from broad net fishing into targeted surgery. They’re making treatments more effective, safer, and faster to approve. But they’re also making access more complicated. The system works better for patients who can get tested quickly, live near specialized centers, and have the resources to navigate the paperwork.

The goal is precision. The challenge is equity. As these tools become standard, we need systems that don’t leave behind patients in rural areas, low-income communities, or developing countries. Until then, knowing how biomarkers work isn’t just helpful-it’s essential.