Anamorelin HCl in the Treatment of Non-Small Cell Lung Cancer - Cachexia (NSCLC-C): An Extension Study;(ROMANA-3)

Unexpected and rapid weight loss is universally recognized as a sign of
disease. The importance of weight loss as both a symptom of cancer and
contributor to morbidity and mortality from the disease has been recognized for
many years. Up to 80% of terminally ill patients with cancer develop cachexia,
which is often the direct cause of death. Despite the significant importance of
cancer cachexia, treatments are lacking. The drugs most commonly employed on an
off-label basis are the appetite stimulants megestrol acetate and dronabinol,
however, the majority of their induced weight gain is fat, not LEAN BODY MASS.
Anamorelin HCl, by virtue of its ghrelin agonist activity and growth hormone
(GH) releasing effects, serves a dual role in the reversal of cancer induced
anorexia and cachexia. Anamorelin HCl is an orally active ghrelin mimetic and
GH secretagogue. Growth hormone and GH secretagogues have a broad array of
beneficial actions on various body systems, characterized by anabolic effects
on Lean Body Mass and bone. The ghrelin mimetic, MK-7677, increases body weight
and reverses the negative nitrogen balance induced by starvation in healthy
volunteers; these effects are independent of its orexigenic effects. Acute
administration of ghrelin to cancer patients exhibiting anorexia and weight
loss increases appetite and food intake.
In Phase II clinical studies conducted by Helsinn Therapeutics, Anamorelin HCl
was administered to patients with cancer-induced cachexia, and demonstrated an
increase in Lean Body Mass, handgrip strength (HGS), and directional benefit in
patient-reported outcomes. The non-peptidic small molecule Anamorelin HCl
offers the promise of an orally available drug.
Weight loss with cachexia is a common presenting sign in NSCL-C. Overall the
patients with weight loss had a significantly lower response rate, shorter
progression free survival, and shorter overall survival than those not
reporting weight loss.

Based on the data available, Anamorelin HCl produces an increase in total body
weight and Lean Body Mass in patients with advanced cancer, and specifically in
patients with NSCLC, in addition to increasing muscle strength and improving
quality of life measures. Therefore, the 100 mg daily dosing and study
duration for 12 weeks was selected based on both the safety and efficacy data
obtained in previous Anamorelin HCl clinical trials, and a low survival rate in
NSCLC patients.
The primary purpose of this extension trial is permit patients to have the
option to continue to receive randomized study drug for an additional 12 weeks.
At the same time the effect of Anamorelin HCl will be measured on Body weight
and on muscle strength as measured by Hand Grip Strength in patients with
advanced NSCLC-C.

This study is an extension study of HT-ANAM-301 with Anamorelin HCl in NSCLC-C
patients.
A Randomized, Double-Blind, Placebo-Group extension study to assess the Safety
and Efficacy of Anamorelin HCl in Patients with NSCLC-C.

Patients who completed dosing in the original trial will have the option of
continuing in this separate double-blind extension study (HT-ANAM-303) in which
patients will continue to be administered Anamorelin HCl 100 mg QD or placebo
QD for an additional 12 weeks. The study will be approximately 17 weeks in
duration including a screening period of up to 1 week, a 12-week treatment
period and a 4-week follow-up period.

Patients are allowed to initiate a new chemotherapy and/or radiation therapy
regimen during the 12-week treatment period.

Investigational drug is Anamorelin HCl; 100 mg tablets; oral administration QD
for 12 weeks, at least 1 hour before the first meal of the day. Subjects will
have their blood drawn at 3 visits.

The study consists of a period of 17 weeks with 1) a screening period of up to
1 week, 2) a dubbel blind treatment period of 12 weeks and 3) a follow-up
period of 4 weeks. There will be 6 visits in total. After this the patient will
be tracked to register survival according their original protocol HT-ANAM-301.
Blood will be drawn at 3 visits. There will be 1 physical examination and 2
ECGs. The Hand Grip Strenght will be measured 2 times.

Anamorelin HCl has been studied in approximately 156 healthy volunteers and in
approximately 254 patients with cancer. Side effects that were reported
frequently (in more than 10% of patients) with the use of the study drug are
the following: swelling of the hands or feet, diarrhea, nausea, constipation,
weakness, fever, and increased blood sugar. Infrequent side effects (occurring
in fewer than 10% of patients) include: decreases in blood pressure following
the first dose and increases in liver function tests. The studies conducted so
far are not large enough to determine if there is an effect (either improvement
or worsening) of Anamorelin HCl on either overall survival or tumor growth. As
such the effect of the study drug on survival is not yet known.