Press Release: Novartis reports clinically relevant improvement in median overall survival data in final analysis of pivotal NETTER-1 study with targeted rad...

-- At final analysis, study showed clinically relevant improvement in median

overall survival with a difference of 11.7 months between arms (Hazard

ratio (HR): 0.84 with 95% CI: (0.60, 1.17) (p=0.30, two-sided))1

-- No new safety signals emerged in long-term follow-up with median of 6.3

years; safety profile consistent with previously reported results1

-- Previously reported primary analysis demonstrated statistically

significant improvement in progression free survival2

-- Novartis is committed to reimagining cancer through radioligand therapy

with more than 15 dedicated research and discovery programs; recent

investments and partnerships further strengthen platform capabilities

Basel, June 3, 2021 -- Novartis today reported the final analysis from

the NETTER-1 phase III study comparing treatment using Lutathera(R)

(INN: lutetium (177Lu) oxodotreotide / USAN: lutetium Lu 177 dotatate)

plus 30 mg octreotide LAR to 60 mg of octreotide LAR in patients with

midgut neuroendocrine tumors. The previously reported primary analysis

of the trial demonstrated a statistically significant improvement in

progression free survival (PFS) (HR: 0.18*, p < 0.0001)(3). In the

final analysis of overall survival, a secondary objective of the trial,

treatment with Lutathera resulted in a clinically relevant prolongation

in median overall survival of 11.7 months [48.0 months (95%CI:

37.4-55.2) compared to the control arm (36.3 months (95%CI:

25.9-51.7)](1.) While this analysis did not reach statistical

significance (Hazard ratio for OS (HR): 0.84 with 95% CI: (0.60, 1.17)

(p=0.30, two-sided))(1), the analyses of overall survival may have been

impacted by multiple factors, including the crossover of patients from

the control arm receiving subsequent radioligand therapy (36% of

patients) as well as heterogenous subsequent anti-cancer treatments in

both study arms(1). No new safety signals emerged in the final

analysis(1). These results will be presented during the 2021 American

Society of Clinical Oncology (ASCO) Annual Meeting on June 4.

Jonathan Strosberg, MD, Principal Investigator and Associate Professor,

Section Head, Neuroendocrine Tumor Program at Moffitt Cancer Center,

said, "Lutathera plus long-acting octreotide was associated with a

nearly 12-month difference in median overall survival compared to

high-dose long-acting octreotide in these difficult to treat patients

with inoperable midgut NETs progressing under standard dose octreotide

LAR treatment. While not statistically significant, I consider this

difference to be clinically relevant for these patients. It is also

important to emphasize that PFS was the primary endpoint of this study.

Moreover, 36% of patients in the control arm crossed over to receive

subsequent radioligand treatment, which may have impacted the comparison

of survival between both study arms."

"We are proud of our 30-year legacy as an innovator for patients in the

neuroendocrine tumor community," said John Tsai, Head of Global Drug

Development and Chief Medical Officer for Novartis. "Since its approval

by the European Commission in 2017 and the FDA in 2018, Lutathera has

been administered to more than 9,000 gastroenteropancreatic

neuroendocrine tumor (GEP-NET) patients in Europe and the United

States(1). We believe in the potential of targeted radioligand therapy

and are investing in new discovery and expansion of this important

platform, including exploration of new radioisotopes and combinations

with complementary mechanisms of action, such as immunotherapy and

inhibitors of DNA damage response."

At this final analysis, no new safety signals emerged in the long-term

safety follow-up with a median of 6.3 years. In terms of secondary

hematological malignancies, no new cases of MDS or acute leukemia were

reported in the long term follow up(4).

Radioligand therapy combines a targeting compound that binds to

receptors expressed by tumors and a radioactive isotope, causing DNA

damage that inhibits tumor growth and replication and may lead to cell

death(5) (-) (7). In the case of Lutathera, it binds to somatostatin

receptor type 2, which is over-expressed on certain types of cells, such

as gastroenteropancreatic neuroendocrine tumor cells(8,9).

Novartis has established global expertise and specialized supply chain

and manufacturing capabilities across its network of four radioligand

therapy production sites, and is further increasing capacity to ensure

delivery of future targeted radioligand therapies to patients in need.

Novartis is the only pharmaceutical company which is pursuing four

different cancer treatment platforms. These include targeted radioligand

therapy, cell and gene therapy, targeted therapy and immunotherapy, with

an opportunity to combine these platforms for the best outcomes for each

cancer patient.

Visit https://www.hcp.novartis.com/virtual-congress/a-2021/ for the

latest information from Novartis, including our commitment to the

Oncology community, and access to our ASCO21 Virtual Scientific Program

data presentations (for registered participants).

* HR: 0.21 (0.13, 0.32) in the US Package Insert

About NETTER-1

NETTER-1 is a Phase III international, multicenter, controlled,

randomized study that compared treatment using Lutathera(R) every eight

weeks plus best standard of care (octreotide LAR 30 mg) to 60 mg of

octreotide LAR (dosed every four weeks) in patients with inoperable

midgut NETs progressing under standard dose octreotide LAR treatment and

overexpressing somatostatin receptors(3).

The primary endpoint was to compare the progression-free survival (PFS)

after treatment with Lutathera(R) plus octreotide LAR 30 mg versus

octreotide LAR 60 mg using RECIST 1.1 criteria(3). Secondary trial

endpoints included comparing objective response rate, overall survival,

time to tumor progression, duration of response and safety between the

two study arms(3).

About GEP-NETs

Neuroendocrine tumors (NETs) are a type of cancer that originate in

neuroendocrine cells throughout the body. NETs are commonly considered

slow-growing malignancies. However, some NETs are associated with rapid

progression and poor prognosis(1) (0-11). In many cases, NET diagnosis

is delayed until patients have advanced disease(12). Symptoms such as

fatigue, diarrhea, and abdominal pain can occur on a daily basis(1) (3)

. Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are subdivided

into two categories: tumors of the gastrointestinal (GI) tract and

pancreas(1) (4). There is a need for additional treatment options for

inoperable or advanced GEP-NET, including those who have progressed

while taking first-line somatostatin analogs.

The estimated age-adjusted incidence, or rate of new cases of NETs in

the United States is approximately 6.98/100,000 per year (as of 2012),

while the estimated 20-year limited-duration prevalence for 2014, based

on the National Cancer Institute's Surveillance, Epidemiology, and End

Results (SEER) database, was 171,321(11). Even though NETs have

historically been considered to be rare (orphan disease), their

incidence has grown over 500% over the last 3 decades (10) (,) (11) (,)

(12) (,) (1) (5).

About Lutathera(R)

Lutathera(R) (lutetium Lu 177 dotatate) is an Advanced Accelerator

Applications product approved in the United States for the treatment of

somatostatin receptor-positive gastroenteropancreatic neuroendocrine

tumors (GEP-NETs), including foregut, midgut and hindgut neuroendocrine

tumors in adults(1) (6).

Lutathera(R) (lutetium ((177) Lu) oxodotreotide) is also approved in

Europe for the treatment of unresectable or metastatic, progressive,

well differentiated (G1 and G2), somatostatin receptor positive

gastroenteropancreatic neuroendocrine tumors (GEP-NETs) in adults(3).

Important Safety Information

LUTATHERA(R) (lutetium Lu 177 dotatate) is a prescription medicine used

to treat adults with a type of cancer known as gastroenteropancreatic

neuroendocrine tumors (GEP-NETs) that are positive for the hormone

receptor somatostatin, including GEP-NETs in the foregut, midgut, and

hindgut.

LUTATHERA is associated with some serious safety considerations, and in

some cases these may require a healthcare provider to adjust or stop

treatment. Treatment with LUTATHERA will expose patients to radiation

which can contribute to long-term radiation exposure. Overall radiation

exposure is associated with an increased risk for cancer. The radiation

will be detectable in urine for up to 30 days following administration

of the drug. It is important to minimize radiation exposure to household

contacts consistent with good radiation safety practices as advised by

your healthcare provider. Treatment with LUTATHERA increases the risk of

myelosuppression, a condition in which bone marrow activity is decreased,

resulting in a drop in blood cell counts. You may experience

blood-related side effects such as low red blood cells (anemia), low

numbers of cells that are responsible for blood clotting

(thrombocytopenia), and low numbers of white blood cells (neutropenia).

Speak with your healthcare provider if you experience any signs or

symptoms of infection, fever, chills, dizziness, shortness of breath or

increased bleeding or bruising. Other serious conditions that you may

develop as a direct result of treatment with LUTATHERA include blood and

bone marrow disorders known as secondary myelodysplastic syndrome and

cancer known as acute leukemia. Your healthcare provider will routinely

check your blood cell counts and tell you if they are too low or too

high. Treatment with LUTATHERA will expose kidneys to radiation and may

impair their ability to work as normal. You may be at an increased risk

for kidney problems after LUTATHERA treatment if you already have kidney

impairment before treatment. In some cases, patients have experienced

(MORE TO FOLLOW) Dow Jones Newswires

June 03, 2021 17:05 ET (21:05 GMT)