Phase 1 Clinical Trials 2026: First-in-Human Studies and Early Drug Development

The common picture of Phase 1 as a last-resort situation for desperate patients is outdated — and partly wrong to begin with. For oncology specifically, the risk calculus changed substantially as targeted agents replaced broad cytotoxics. A tyrosine kinase inhibitor in a Phase 1 dose escalation, administered to a patient with EGFR-mutant lung cancer at a dose that produces adequate plasma concentration, may produce tumor shrinkage. Response rates of 10–20% in Phase 1 oncology studies are real. That doesn't mean Phase 1 should be entered without careful consideration of the risks, but the question "what is this drug likely to do to me?" has a more optimistic expected answer in 2026 than it did twenty years ago. The landscape has also fractured: healthy volunteer Phase 1 studies for non-oncology drugs are a completely different experience from patient Phase 1 cancer trials, and understanding which you're considering changes everything.

What Phase 1 Trials Actually Test — and How They're Designed

Before a drug enters Phase 1, FDA must have reviewed and not placed a clinical hold on an Investigational New Drug (IND) application that documents the mechanism, preclinical efficacy and toxicology, proposed starting dose, and monitoring plan. The starting dose is calculated based on preclinical toxicology data — typically 1/10th of the most severely toxic dose in the most sensitive animal species, with additional safety factors for novel mechanisms. This calculation is more complex for immunomodulatory drugs, which is why the BIA 10-2474 disaster in 2006 — six healthy volunteers with severe cytokine storm from a CD28 superagonist — has had lasting effects on how immunomodulatory starting doses are selected and how early Phase 1 cohorts are monitored.

The traditional "3+3" dose escalation design — enroll 3 patients, wait for dose-limiting toxicities (DLTs), escalate or not — is increasingly giving way to model-based Bayesian designs including the BOIN (Bayesian Optimal Interval) and mTPI (modified Toxicity Probability Interval) designs. These use Bayesian statistical updating after each cohort to make better-informed decisions about the next dose level. The practical advantages are significant: they find the optimal dose with fewer patients exposed to sub-therapeutic or excessive doses, and they're more adaptive to the actual emerging toxicity data. Most major oncology Phase 1 programs running in 2026 use model-based designs.

For most modern targeted oncology agents, the goal is not the maximum tolerated dose (MTD) — it's the recommended Phase 2 dose (RP2D) based on pharmacokinetic/pharmacodynamic modeling. Kinase inhibitors, monoclonal antibodies, and ADCs often have activity at doses that don't cause significant toxicity, so toxicity-based escalation doesn't necessarily find the biologically optimal dose. PK/PD modeling that tracks drug concentration against tumor marker responses guides dose selection more rationally than toxicity endpoints alone.

Patient Phase 1 vs Healthy Volunteer Phase 1: A Meaningful Distinction

Oncology Phase 1 trials enroll patients with advanced cancer who have exhausted standard treatment options. The risk-benefit rationale is clear: these patients are already in a high-risk clinical situation, the preclinical data justifies the trial, and the potential for benefit exists. Non-oncology Phase 1 trials — for cardiovascular drugs, CNS agents, antibiotics, metabolic treatments, vaccines — typically enroll healthy volunteers. Exposing healthy people to experimental oncology drugs isn't ethically justified; exposing healthy people to an experimental antihypertensive with a clean preclinical safety profile to characterize its PK is a different calculation entirely.

Healthy volunteer Phase 1 studies are conducted at specialized clinical pharmacology units — dedicated facilities with intensive monitoring, frequent PK blood sampling, 24-hour physician coverage, and strict confinement periods where participants stay on-site to enable dense sampling. The experience involves frequent blood draws (sometimes every 15–30 minutes post-dose during the first several hours), possible ECG monitoring, meals controlled to study protocol specifications, and limitations on outside contact during confinement. Compensation is typically $200–$400/day for the duration of the stay, plus additional amounts for outpatient follow-up visits. For a single-dose PK study with 1 overnight stay plus 2–3 outpatient visits, total compensation might be $1,500–$2,500. For a multi-period crossover study with multiple confinement periods over several months, compensation can reach $10,000–$15,000.

What Participants in Phase 1 Cancer Trials Experience

Phase 1 cancer trial participation differs substantially from healthy volunteer studies. Patients receive treatment on a cycle schedule — for example, IV infusion every 3 weeks — with additional assessments beyond what standard oncology care would involve: PK blood draws before and at multiple time points after each infusion in the first cycle, pharmacodynamic biomarker assessments (including tumor biopsies at baseline and on-treatment in some programs), and more frequent imaging than routine surveillance. Visit burden is highest in the first cycle, when the DLT observation period runs and PK data is collected most intensively.

DLTs — dose-limiting toxicities, prespecified adverse events of sufficient severity to trigger dose escalation rules — are assessed during the first cycle. If a DLT occurs in one of the first three patients at a dose level, additional patients are enrolled at that level before escalation proceeds. The DSMB reviews accumulating safety data before each dose escalation and can mandate additional patients, require dose deescalation, or halt the trial. No patient is escalated to a dose level the safety monitoring process hasn't reviewed. DLT definitions are prespecified in the protocol — typically Grade 3+ non-hematologic toxicity or Grade 4 hematologic toxicity — and are graded by the NCI Common Terminology Criteria for Adverse Events (CTCAE).

The Most Active Phase 1 Areas in 2026

Oncology drives roughly 60% of all Phase 1 activity, but the scientific diversity within oncology Phase 1 is wider than it's ever been. The fastest-growing category is antibody-drug conjugates (ADCs) — monoclonal antibodies conjugated to cytotoxic payloads via chemical linkers, delivering potent cell-killing agents directly to antigen-expressing tumor cells. Trastuzumab deruxtecan (T-DXd, DESTINY trials) and sacituzumab govitecan (Trodelvy) have moved from Phase 1 to registrational Phase 3 and approval in breast and bladder cancer, demonstrating the pathway. Over 100 Phase 1 ADC trials are currently recruiting, targeting antigens across solid and liquid tumors with varied payloads and linker chemistries.

Bispecific T cell engaging antibodies — molecules that bind CD3 on T cells and a tumor antigen simultaneously, redirecting T cells to kill tumor cells — have produced remarkable results in hematologic malignancies. Tarlatamab for small cell lung cancer (DLL3 × CD3) and mosunetuzumab for follicular lymphoma (CD20 × CD3) have advanced to approval from Phase 1/2 data. Over 50 novel bispecific programs are in Phase 1, spanning solid and liquid tumor applications, with CD3-independent NK cell engagers also entering early trials.

In vivo gene editing programs represent the most scientifically novel Phase 1 work in 2026. Intellia's NTLA-2001 (CRISPR KO of TTR gene for ATTR amyloidosis) and NTLA-2002 (KLKB1 KO for hereditary angioedema) have demonstrated durable gene editing from single IV infusions in Phase 1/2 — meaning a single treatment has permanently modified a gene in the liver, producing sustained protein knockdown without ongoing medication. Beam Therapeutics BEAM-101 uses base editing of the BCL11A enhancer to reactivate fetal hemoglobin for sickle cell disease. Each of these programs required novel safety monitoring frameworks for editing efficiency, off-target editing, and immune responses to delivery systems — there's no prior playbook for how to run first-in-human gene editing trials.

How to Find Phase 1 Clinical Trials

ClinicalTrials.gov filters by Phase (select "Early Phase 1" or "Phase 1"), disease condition, and recruiting status. For patients with advanced cancer who have progressed on standard options, the most effective approach is a consultation at a major cancer center with a dedicated Phase 1 program. MD Anderson, MSKCC, Dana-Farber, Johns Hopkins Sidney Kimmel, Penn Medicine Abramson, Stanford, and UCSF all have clinical pharmacologists and early drug development specialists who review multiple concurrent protocols simultaneously to identify the best match for a given patient. This service — sometimes called a "Phase 1 consultation" — is distinct from standard oncology consultation and is specifically focused on trial access. Many of these programs will review records from outside institutions to assess trial eligibility before a patient travels.

The NCI CTEP (Cancer Therapy Evaluation Program) maintains a searchable database of NCI-sponsored Phase 1 trials. For patients outside major metropolitan areas, NCCN guidelines explicitly list clinical trial participation as a Category 1 recommendation for patients with advanced cancer who have progressed on standard therapy — and most comprehensive cancer centers have remote evaluation services that can identify accessible options without requiring an initial in-person visit.

Key Takeaways

• Phase 1 trials test safety and PK first, but modern targeted oncology Phase 1 studies see clinical responses in 10–20%+ of participants — they are legitimate treatment options for patients who have exhausted approved therapies, not merely experimental last resorts.
• Bayesian dose escalation designs (BOIN, mTPI) are replacing "3+3" in most well-run Phase 1 programs, finding the RP2D more efficiently and with fewer patients at sub-therapeutic doses.
• The distinction between healthy volunteer Phase 1 and patient Phase 1 is fundamental — the experience, compensation structure, risk profile, and participant population are entirely different.
• The most active Phase 1 categories in 2026 are ADCs (100+ studies), bispecific T cell engagers (50+), and in vivo CRISPR/base editing programs seeking durable genetic correction from a single treatment.
• A Phase 1 consultation at a major cancer center — specifically with a clinical pharmacologist who reviews multiple concurrent early-phase protocols — is the most effective way for a patient with advanced cancer to identify relevant Phase 1 options.