FDA draft guidance sets out how early-phase solid tumor protocols should handle eligibility, dosing and consent

A draft guidance dated November 2026, announced in a Federal Register notice of November 12, 2026, gives sponsors and clinical investigators recommendations for a first-in-human study, or a protocol for a drug or biologic with limited human experience, in solid tumors. The recommendations "are based on common issues identified during the review of INDs," the draft says, and it does not address hematologic malignancies. Comments are due January 11, 2027, under docket FDA-2026-D-13432, so the FDA considers them before it begins work on the final version.

A patient's path through an early-phase solid tumor protocol, as the draft sets it out

Who can enroll In general no upper age limit, no time-based washout unless justified, and renal and QTc cutoffs matched to the drug.
Consent Therapies with an overall survival benefit named in the consent form; written re-consent at progression before treatment continues.
Dosing A prespecified rule-based or model-based escalation design, and a dose-limiting toxicity window of at least one cycle.
Visit schedule Intensive pharmacokinetic sampling after the first dose and at steady state; ECGs around the anticipated time of maximum concentration.
Follow-up About 90 days after treatment discontinuation for all patients; at least 5 years for radiolabeled products; up to 15 years for gene therapy.

Source: FDA, Early-Phase IND Protocol Recommendations for Solid Tumors, draft guidance (November 2026).

The draft contains nonbinding recommendations, the FDA's guidance page notes. For the staff who screen, consent, dose and sample patients in a phase 1 trial, it reads as a working list.

Who can enroll

Unnecessarily restrictive eligibility criteria "may slow patient accrual, limit patient access to early-phase trials," and yield results of limited applicability, the draft says. Its recommendations include:

In general, no upper age limit; a proposed limit needs adequate justification. Adolescents may be enrolled concurrently with adults after some initial adult pharmacokinetic and toxicity data are obtained, absent development-specific safety concerns.
No time-based washout and recovery periods unless scientifically justified. Eligibility after prior therapy should rest on recovery from clinically significant adverse events.
Renal cutoffs matched to the drug: a creatinine clearance or eGFR of 60 mL/min or greater for small molecules and antibody-drug conjugates, and 30 mL/min or greater for biologics above 69 kDa.
QTc exclusions matched to the drug: above 470 milliseconds for small molecules and antibody-drug conjugates, above 450 for small molecules with high potential for QTc prolongation, and above 480 for other biologics. The FDA does not recommend different cutoffs by sex.
Thoughtful consideration of including patients with brain metastases, and patients with HIV, hepatitis B or hepatitis C.

For autologous cell and gene therapies, eligibility should be confirmed at lymphodepletion and at product administration.

Renal and QTc cutoffs the draft suggests, by product type

Criterion	Product type	The draft suggests
Renal function (creatinine clearance or eGFR)	Small molecules and antibody-drug conjugates	60 mL/min or greater
Renal function (creatinine clearance or eGFR)	Biologics above 69 kDa	30 mL/min or greater
QTc exclusion	Small molecules and antibody-drug conjugates	Above 470 milliseconds
QTc exclusion	Small molecules with high potential for QTc prolongation	Above 450 milliseconds
QTc exclusion	Biologics other than antibody-drug conjugates	Above 480 milliseconds
QTc exclusion	By sex	No different cutoffs

Renal function (creatinine clearance or eGFR)

Product type

Small molecules and antibody-drug conjugates

The draft suggests

60 mL/min or greater
Product type

Biologics above 69 kDa

The draft suggests

30 mL/min or greater

QTc exclusion

Product type

Small molecules and antibody-drug conjugates

The draft suggests

Above 470 milliseconds
Product type

Small molecules with high potential for QTc prolongation

The draft suggests

Above 450 milliseconds
Product type

Biologics other than antibody-drug conjugates

The draft suggests

Above 480 milliseconds
Product type

By sex

The draft suggests

No different cutoffs

Source: FDA draft guidance (November 2026), eligibility criteria on renal function and the QT interval.

Where therapies with a demonstrated overall survival benefit exist for the disease, "these therapies should be explicitly stated in the informed consent document by name," the draft says.

When a protocol lets patients stay on the investigational drug after radiographic progression, patients with alternative options should be re-consented in writing. That document should detail the alternative FDA-approved therapies, participation in alternative trials, and the potential clinical benefit the patient may be foregoing. It should be signed at the time of progressive disease, before treatment continues.

How dosing moves

The draft asks for a prespecified rule-based or model-based escalation design. In accelerated titration with single-patient cohorts, it says to switch to larger cohorts, such as a minimum of 3 patients, after any Grade 2 or higher adverse event regardless of attribution, unless clearly related to the underlying disease or an extraneous cause. Intra-patient dose escalation should occur only if Grade 2 or lower toxicity was observed in the previous cycle, and only up to the highest cleared dose level.

Where expected toxicities make dosing several patients at once an unreasonable risk, sponsors may need a plan to stagger patients within and between cohorts. In first-in-human studies with risks of acute respiratory or hemodynamic compromise, inpatient monitoring may be warranted for the initial patients.

For dose-limiting toxicity, all adverse events that occur or worsen after one dose "should be considered at least possibly related to the study drug regardless of investigator/sponsor/safety review committee causality assessment," except those clearly related to disease progression or extraneous causes. The evaluation window should generally be at least one cycle, such as 21 or 28 days. An adverse event that requires a hold should return to Grade 1 or baseline within 14 days before therapy resumes.

The dosing rules the draft sets, from escalation design to dose holds

Escalation design Prespecified, rule-based or model-based.
Single-patient cohorts In accelerated titration, switch to larger cohorts, such as a minimum of 3 patients, after any Grade 2 or higher adverse event regardless of attribution.
Dose-limiting toxicity window Generally at least one cycle, such as 21 or 28 days; adverse events after one dose count as at least possibly related.
Intra-patient dose escalation Only if Grade 2 or lower toxicity was observed in the previous cycle, and only up to the highest cleared dose level.
Dose hold The adverse event returns to Grade 1 or baseline within 14 days before therapy resumes.

Source: FDA draft guidance (November 2026), dose escalation trial design and dose-limiting toxicity criteria.

What the visit schedule holds

The sampling recommendations shape the calendar:

Pharmacokinetics: intensive sampling after the first dose and at steady state or after multiple doses, plus sparse sampling throughout the study.
ECGs: for small molecules, antibody-drug conjugates and some biologics, monitoring before dosing and around the anticipated time of maximum concentration, after the first dose and at steady state or after multiple doses. Triplicate ECGs can support QT-concentration analysis.
Immunogenicity: for biologics, samples collected before dosing at each cycle for at least the first three cycles, then every other cycle for three to four cycles, then every four cycles.
Food: typically a modified fasted condition, at least 1 hour before and 2 hours after a meal.

Follow-up runs longer for some products. All patients should be monitored for approximately 90 days after treatment discontinuation, or longer based on the mechanism of action, for late-onset toxicities such as delayed immune-related ones. Patients who receive radiolabeled products should be followed for at least 5 years after the last dose, and gene therapy follow-up of up to 15 years may be required.

For expansion cohorts, the draft prefers a new IND once activity and safety signals appear in one tumor type, rather than expanding that cohort beyond 40 patients under the early-phase IND.

How long follow-up runs under the draft

Patients	Follow-up
All patients	Approximately 90 days after treatment discontinuation, or longer based on the mechanism of action, for late-onset toxicities
Patients who receive radiolabeled products	At least 5 years after the last dose
Patients who receive gene therapy products	Up to 15 years of long-term follow-up may be required

All patients

Follow-up

Approximately 90 days after treatment discontinuation, or longer based on the mechanism of action, for late-onset toxicities

Patients who receive radiolabeled products

Follow-up

At least 5 years after the last dose

Patients who receive gene therapy products

Follow-up

Up to 15 years of long-term follow-up may be required

Source: FDA draft guidance (November 2026), dose-limiting toxicity criteria and safety monitoring.

Where these trials run

When this analysis was prepared, the registry at clinicaltrials.gov listed:

651 recruiting studies that list phase 1 among their phases, match a "solid tumor" condition search and have at least one United States location (registry query);
531 of those with an industry lead sponsor (registry query);
256 of those that also list phase 2 (registry query).

The counts come from a condition search, so they show a pool of listed studies, not every early-phase solid tumor trial.

What remains uncertain

The draft is labeled not for implementation, and neither it nor the notice gives a date for a final version. Its eligibility and sampling sections each say they are not an exhaustive list (FDA draft guidance).