new data on super herceptin / trastuzumab-dm1 study

[runtolive]

On September 5, 2008, Genentech reported trastuzumab-DM1 (T-DM1) Phase II clinical data at the American Society of Clinical Oncology (ASCO) Breast Cancer Symposium being held in Washington, DC. T-DM1 comprises ImmunoGen’s DM1 cell-killing agent linked to Genentech’s HER2-targeting antibody, trastuzumab, and is being developed by Genentech under a collaboration agreement with ImmunoGen.

The interim data reported were from the T-DM1 Phase II trial that began in July 2007. The trial is designed to evaluate T-DM1, administered at 3.6 mg/kg every 3 weeks, in approximately 100 efficacy-evaluable patients with HER2-positive metastatic breast cancer that progressed on treatment with HER2-directed therapy plus chemotherapy.

The study protocol included an interim analysis of activity in the first 30 efficacy-evaluable patients and it is these findings which were reported today.

Baseline demographic, disease characteristics and prior therapy information were reported for a total of 31 individuals, as there was one non-evaluable patient treated as well as the 30 evaluable patients. All of these patients had metastatic disease, with 19 (61%) having at least 3 distinct metastatic sites. They all had previously been treated with Herceptin (trastuzumab) plus chemotherapy, with a median time on Herceptin of 76.1 weeks (range: 12-379 weeks). Additionally, 13 (41.9%) of these patients also had received Tykerb (lapatinib) plus chemotherapy. The median duration of treatment with Tykerb among the patients who had received it was 25.3 weeks (range: 14-106 weeks).

The presentation conclusions focused on the findings relevant to the established interim analysis criteria. It was noted that 9 objective responses, as determined by an Independent Review Facility (IRF), were reported among the first 30 evaluable patients. This surpassed the activity criterion for study continuation, which was 5 IRF-assessed objective responses. It also was concluded that the safety profile seen with T-DM1 in this trial to date is similar to that observed in the Phase I study.

The findings section of the presentation included information on the activity of T-DM1 as assessed by a study investigator (the approach used in the T-DM1 Phase I study) as well as the IRF-assessment data. Based on investigator assessment, among the 30 evaluable patients, 1 had a complete response (CR), 12 had a partial response (PR), and 10 had stable disease (SD). The CR was ongoing through Cycle 10 when the patient discontinued treatment under the guidance of her physician due to her complete response. Eight (8) of the 12 PRs and 6 of the 10 SDs were ongoing at the time of data cut-off for presentation (May 6, 2008). The patient on T-DM1 the longest at that time had received 12 treatment cycles and had an ongoing PR.

run to live

[runtolive]

marsha / is this you they are talking about.. i recall you saying you hit NED in may 2008.

[doh2pa]

Thanks so much for posting this. I am hanging tough with Gemzar, Avastin and Tykerb right now but this DM-1 study is on deck as my next thing to try. So I am so happy to hear the positive results.

[runtolive]

doh... hopefully you wont need it. but if u do, it appears its doing the trick.. who else is on the trastuzumab-dm1, and how have you been doing lately. this drug is on the road to approval. another drug to help us..

run

[Barbara H.]

Hi,
It's not going to be approved for a few years. There is a new phase 2 trial opening up at the Dana Farber. I am doing well on the phase 1 trial. My tumor markers remain normal and I have no bone pain. Unfortunately, it takes a while for bones to hear so it is difficult to know what is going on with the cancer. Fortunately, the bones are not getting worse. As a result, would not have been possible for me to get into a phase 2 trial because my disease is no measurable. I feel fortunate to be in the phase one trial and to have few side effects. I feel no different than when I was just on Herceptin.

Last week I had a CT scan and the inflammation in my lung was stable. I am therefore allowed to wait until the next 6 week scan. As long as the inflammation is stable or better I won't have to have the lung biopsy. I am greatful for this 6 weeks because school started last week.

I have been on this trial for year this month. As long as I am doing well I am allowed to stay on the drug. I would certainly reccommend it to anyone who can meet the criteria. Although some members on this board have had a difficult time with it, my oncologist says that most patients do not. I believe that he is one of the leaders for investigating this trial.

Best wishes,
Barbara H.

[runtolive]

barb.. how are the other ladies doing in the weekly dosed arm of the trial you took part in at Dana Farber

[Barbara H.]

As far as I have heard the majority are doing very well.
Barbara H.

[RobinP]

You Are Paving The Way To New And Innovative Treatment! So Far Dmi With Herceptin Looks Very Promising.

[runtolive]

Trastuzumab-DM1 - a 'smart bomb' for breast cancer treatment

Published: Sunday, 7-Sep-2008 Printer Friendly Email to a Friend
Drug Trials

Sarah Cannon Research Institute (SCRI) investigators have found that "smart bomb" therapies are effective in treating breast cancer patients while minimizing side effects.

Howard A. Burris III, M.D., SCRI's chief medical officer, is presenting interim Phase II clinical trial results of a drug named Trastuzumab-DM1 (T-DM1), a novel antibody drug conjugate, at the American Society of Clinical Oncology's Breast Cancer Symposium in Washington, D.C.
T-DM1 is built from the widely used antibody Herceptin. T-DM1 combines Herceptin's HER2 blocking activity with a targeted intracellular delivery of a potent anti-microtubule agent directly into HER2-positive breast cancer cells. In 20 percent of breast cancer cases, the patient's cancer has too much of the HER2 protein, which makes the cancer cells grow and divide more quickly. T-DM1 is designed to focus delivery of treatment to HER2-positive cancer cells and limit delivery to surrounding healthy tissue.
Dr. Burris and his team were the first oncologists to treat patients with T-DM1 in December 2006. Minimal toxicities have been observed in the trial to date.
"Physicians call it a 'smart bomb' because it's designed to hit the target cancerous cells with minimal collateral damage to its neighboring non-cancerous cells," Dr. Burris said.
Thirty-one patients with HER2-positive metastatic breast cancer whose tumors had progressed on prior HER2-directed therapy in the trial received 3.6 mg/kg of T-DM1 by IV every three weeks. The interim findings of the Phase II study include evidence of tumor shrinkage in some patients.
Murfreesboro, Tenn. resident Nancy Fann, 64, had been on at least three chemotherapy treatments since cancer had spread from her lung to her liver and breast, but the tumors kept coming back. In May 2007 she enrolled in the T-DM1 clinical trial.
"The tumors are considerably smaller than they were to begin with," Fann said. "This drug doesn't seem to affect me as much as some of the others I've been on. I don't get sick and I haven't lost my hair."
Denise A. Yardley, M.D., SCRI's director of breast cancer research, also is presenting her research on two trials today at noon. Both trials focus on targeted therapies for patients with HER2-positive metastatic breast cancer.
One trial shows preliminary results from a Phase II trial of a combination of Herceptin and the chemotherapy drug oxaliplatin. Twenty-one patients have enrolled in the trial so far, and early results show the treatment is active with little to no significant side effects seen to date.
The other trial focuses on a combination treatment of Avastin and the chemotherapy drug docetaxel for early-stage, metastatic breast cancer. A cohort of patients with HER2-positive disease also receives Herceptin as part of the study. Data for the first 138 patients enrolled indicate the treatment is reasonably well-tolerated without unexpected side effects.
"As knowledge about tumors and tumor biology grows, we're learning that all breast cancers are not identical," Dr. Yardley said. "These smart new drugs help target treatment specific to certain types of tumors, causing less damage to healthy cells and reducing side effects."
SCRI is one of the largest clinical research programs in the nation, conducting community-based clinical trials in oncology, cardiology, gastroenterology and other therapeutic areas through affiliations with a network of nearly 500 physicians in 24 states. Additionally, SCRI offers management, regulatory and other research support services to drug development sponsors and strategic investigator sites across the country.
http://www.sarahcannonresearch.com/