Because malignant tumors are life-threatening, the death rate from these diseases is high, and
existing therapies have limited effectiveness, it is desirable to provide new, effective anticancer
drugs to patients more expeditiously.
There have been no internationally accepted objectives or recommendations on the design and
conduct of nonclinical studies to support the development of anticancer pharmaceuticals in
clinical trials for the treatment of patients with advanced disease and limited therapeutic options.
Nonclinical evaluations are conducted to:
(1) identify the pharmacologic properties of a pharmaceutical,
(2) establish a safe initial dose level for the first human exposure, and
(3) understand the toxicological profile of a pharmaceutical (e.g., identification of target
organs, exposure-response relationships, and reversibility).
In the development of anticancer drugs, clinical studies often involve cancer patients whose
disease condition is progressive and fatal. In addition, the dose levels in these clinical studies
often are close to or at the adverse effect dose levels. For these reasons, the type, timing, and
flexibility called for in the design of nonclinical studies of anticancer pharmaceuticals can differ
from those elements in nonclinical studies for other pharmaceuticals.
This guidance provides information for pharmaceuticals that are intended to treat cancer in
patients with serious and life threatening malignancies. For the purpose of this guidance, this
patient population is referred to as patients with advanced cancer. The guidance applies to both
small molecule and biotechnology-derived pharmaceuticals (biopharmaceuticals), regardless of
the route of administration. This guidance describes the type and timing of nonclinical studies in
relation to the development of anticancer pharmaceuticals in patients with advanced cancer and
references other guidance as appropriate. It describes the minimal considerations for initial
clinical trials in patients with advanced cancer whose disease is refractory or resistant to
available therapy, or where current therapy is not considered to be providing benefit. The
nonclinical data to support Phase 1 and the clinical Phase 1 data would normally be sufficient for
moving to Phase 2 and into second or first line therapy in patients with advanced cancer. The
guidance also describes further nonclinical data to be collected during continued clinical
development in patients with advanced cancer. When an anticancer pharmaceutical is further
investigated in cancer patient populations with long expected survival (e.g., those administered
pharmaceuticals on a chronic basis to reduce the risk of recurrence of cancer), the
recommendations for and timing of additional nonclinical studies depend upon the available
nonclinical and clinical data and the nature of the toxicities observed.
This guidance does not apply to pharmaceuticals intended for cancer prevention, treatment of
symptoms or side effects of chemotherapeutics, studies in healthy volunteers, vaccines, or
cellular or gene therapy. If healthy volunteers are included in clinical trials, the ICH M3
guidance should be followed. Radiopharmaceuticals are not covered in this guidance, but some
of the principles could be adapted.