August 2015PDF



High-Risk Subset of CLL Patients Shows Benefit in Phase II Trial

A statistically significant percentage of chronic lymphocytic leukemia patients in a phase II clinical trial responded to venetoclax therapy.

The open-label study, sponsored by AbbVie, met its primary endpoint, achieving overall response rates in patients with relapsed/refractory or previously untreated CLL with 17p deletion, according to an independent review analysis.

The study enrolled 157 patients, 107 in the main study cohort evaluating efficacy, and 50 patients in the safety expansion cohort.

The primary efficacy endpoint is overall response rate, and the primary safety endpoints are the number and percentage of patients who experienced treatment-related adverse events, changes in physical exam findings, including vital signs, changes in clinical laboratory test results and changes in cardiac assessment findings.


Lung Cancer

Atezolizumab Immunotherapy Meets Response Endpoint in Phase II NSCLC Study

A phase II study of atezolizumab immunotherapy met its primary endpoint, shrinking tumors in patients with locally advanced or metastatic non-small cell lung cancer whose disease expressed PD-L1.

The study showed the amount of PD-L1 expressed by a person’s cancer correlated with their response to the medicine.

The study, BIRCH, is an open-label, multicenter, single-arm study that evaluated the safety and efficacy of atezolizumab in 667 people. Results from the study will be presented at an upcoming medical meeting, according to the drug’s sponsor, Genentech, a member of the Roche Group.



Drugs and Targets

European Commission Approves Unituxin in Pediatric High-Risk Neuroblastoma

The European Commission granted a marketing authorization for Unituxin (dinutuximab) for the treatment of high-risk neuroblastoma in patients aged 12 months to 17 years, who have previously received induction chemotherapy and achieved at least a partial response, followed by myeloablative therapy and autologous stem cell transplantation.

Unituxin is administered in combination with granulocyte-macrophage colony-stimulating factor, interleukin-2, and isotretinoin.

The European approval was based on demonstration of improved event-free survival and overall survival in a multicenter, open-label, randomized trial (ANBL0032) sponsored by NCI under a Cooperative Research and Development Agreement with the drug’s sponsor, United Therapeutics Corp., and conducted by the Children’s Oncology Group.


Liver Cancer

ThermoDox plus RFA Increase OS By 58 Percent in HEAT Study


Carcinoid Syndrome

Oral Telotristat Etiprate Trial Meets Phase III Primary Endpoint


NCI CTEP-Approved Trials for the Month of August

August 2015
July 2015PDF



Phase II Trial Shows Benefit with Imbruvica In Activated B-cell-like Subtype of DLBCL

A phase II clinical trial identified patients with a specific molecular subtype of diffuse large B-cell lymphoma that are more likely to respond to Imbruvica (ibrutinib) treatment.

In the trial, patients with the activated B-cell-like subtype of DLBCL were more likely to respond to Imbruvica than patients with the germinal center B-cell-like subtype. The trial was jointly conducted by NCI and Pharmacyclics Inc., and was published in Nature Medicine.


Drugs and Targets

FDA Approves Odomzo in Advanced BCC, Kyprolis Combination in Multiple Myeloma

FDA approved Odomzo (sonidegib) capsules for the treatment of patients with locally advanced basal cell carcinoma that has recurred following surgery or radiation therapy, or those who are not candidates for surgery or radiation therapy. Odomzo is marketed by Novartis Pharmaceuticals Corp.

The approval was based on demonstration of a durable objective response rate in an international, multi-center, double-blind, randomized, two-arm, non-comparative trial in patients with locally advanced basal cell carcinoma not amenable to local therapy or metastatic basal cell carcinoma.


Prostate Cancer

Researchers: As Many as 40% of Patients Could be Receiving Overtreatment

As many as 40 percent of patients with lower-risk prostate cancers may be currently receiving overtreatment, according to researchers that examined common treatment practices.

Monitoring men with very low- and low-risk prostate cancers using watchful waiting or active surveillance, or expectant management, is a useful approach for a large number of men with localized tumors and could spare them the debilitating side effects of aggressive treatments that are too often unnecessarily used in this patient population, according to a study led by researchers at UCLA.


Colorectal Cancer

Vectibix Improves OS in Phase III Trial of mCRC


Liver Cancer

Cyramza Trial Fails OS Endpoint; Subgroup Data to Form New Study



Pracinostat/Vidaza Combination Shows Response in Phase II Trial


Bladder Cancer

Study: Robotic Surgery Shows Long-term Results Similar to Traditional Open Surgery


NCI CTEP-Approved Trials for the Month of July

August 2015
June 2015PDF



Adding Imbruvica to Bendamustine/Rituximab Combination Increases PFS in Phase III Trial

Patients with previously treated chronic lymphocytic leukemia or small lymphocytic lymphoma that received Imbruvica (ibrutinib) in combination with bendamustine and rituximab experienced an 80 percent reduction in the risk of progression or death when compared to patients receiving bendamustine, rituximab and placebo in a phase III trial.

Imbruvica patients also experienced a higher overall response rate, including achieving a higher rate of complete responses, after a median follow-up of 17 months.
On March 16, an independent data monitoring committee recommended that the trial, named HELIOS, be unblinded based on clinically meaningful and statistically significant treatment benefit observed in the Imbruvica arm compared to placebo and BR.



Trial: Tafinlar/Mekinist Combination Benefits BRAF V600E/K Mutation-Positive Patients

Data from the phase III COMBI-d study showed a significant survival benefit for patients with BRAF V600E/K mutation-positive metastatic melanoma when treated with the combination of Tafinlar and Mekinist compared to Tafinlar alone.

The final analysis included the 423 patients enrolled in COMBI-d and showed that the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) achieved a statistically significant overall survival benefit compared to Tafinlar monotherapy, with median of 25.1 months compared to 18.7 months, respectively (HR=0.71 [95% CI, 0.55-0.92], p=0.011).


Lung Cancer

Gilotrif Reduces Risk of Death by 19 Percent In Phase III Squamous Cell Carcinoma Trial

Overall survival results from the LUX-Lung 8 trial comparing two EGFR-directed treatments, Gilotrif (afatinib) and Tarceva (erlotinib), in patients with advanced squamous cell carcinoma of the lung progressing after treatment with first-line chemotherapy, demonstrated that treatment with Gilotrif significantly reduced the risk of death by 19 percent, extending the survival of patients to a median of 7.9 months compared to 6.8 months on Tarceva.

Significantly more patients treated with Gilotrif were still alive at one year compared to those treated with Tarceva (36.4 vs. 28.2 percent).


Prostate Cancer

Retrospective Analysis Shows Benefit with Custirsen in mCRPC Patients with Poor Prognosis



Pacritinib Demonstrates Control Of Symptoms in Phase III Trial


Kidney Cancer

Phase II Study Compares Afinitor As Second-Line Treatment Following Various VEGFR Inhibitors and Cytokine Therapy


Pancreatic Cancer

PEGPH20 Shows Doubling of PFS Among Patients with High Levels Of Hyaluronan in Phase II Trial


Breast Cancer

Phase III Prolia Trial Meets Endpoint in Clinical Fractures



Electric Nerve Stimulation Shown to Be as Effective as Pilocarpine in Treating Radiation-Induced Dry Mouth


Drugs and Targets

Lenvatinib Launched in U.K. For Advanced Thyroid Cancer

 NCI CTEP-Approved Trials for the Month of June
June 2015
May 2015PDF


NCI MATCH Trial to Begin Patient Enrollment in July

CHICAGO—NCI’s long-planned, large scale precision medicine trial will open to patient enrollment in July, investigators announced June 1 at the annual meeting of the American Society of Clinical Oncology.

NCI-MATCH: Molecular Analysis for Therapy Choice will assign patients to therapies based on molecular profiles of their tumors, rather than the organ site where their cancer began. The purpose is to determine whether targeted therapies for people whose tumors have specific gene mutations will be effective regardless of their cancer type.

The phase II trial will incorporate more than 20 different study drugs or drug combinations, each targeting a specific gene mutation, to match each patient with a therapy that targets a molecular abnormality in their tumor.


ASCO to Launch its First Clinical Trial: TAPUR

CHICAGO—The American Society of Clinical Oncology announced June 1 that it will move forward with its first-ever clinical trial, a study designed to offer patients with advanced cancer access to molecularly-targeted cancer drugs and to collect data on clinical outcomes to learn the best uses of these drugs outside of FDA-approved indications.

The Targeted Agent and Profiling Utilization Registry, or TAPUR, is a prospective, non-randomized clinical trial that will collect information on the anti-tumor activity and toxicity of commercially available, targeted cancer drugs in a range of cancer types, including any advanced solid tumor, multiple myeloma, or non-Hodgkin lymphoma with a genomic variation known to be a drug target.


Pancreatic Cancer

IMM-101 Combination Improves OS in Metastatic Disease in Phase II Trial

Updated long-term survival results from IMAGE 1, a phase II clinical trial evaluating a combination of IMM-101 and gemcitabine as first-line treatment for advanced pancreatic cancer, found that, in patients with metastatic disease, IMM-101 was associated with improving the probability of survival at 12 months to 24 percent, compared to 11.5 percent in patients receiving gemcitabine alone.

This difference was amplified at 18 months to 18.3 percent for IMM-101-treated patients compared to 2.3 percent in the control group. At 24 months the corresponding survival probabilities were 11 percent and 0 percent, respectively. This is in addition to the previously reported consistent and significant improvements in overall survival and progression free survival in patients with metastatic pancreatic cancer.


Non-Small Cell Lung Cancer

MPDL3280A Immunotherapy Doubles OS in Patients with Highest Levels of PD-L1


Kidney Cancer

Study: Statins Can Improve Survival in Renal Cell Carcinoma


Stomach Cancer

Avastin Combination Improves Survival in Phase II Study


Endometrial Cancer

Phase III ZoptEC Trial to Continue Following Interim Analysis



APD403 Demonstrates Control Of Nausea and Vomiting After Highly Emetogenic Treatments


Drugs and Targets

FDA Grants Orphan Designation For Reolysin in Malignant Glioma

 NCI CTEP-Approved Trials for the Month of May 
June 2015
April 2015PDF



Keytruda Meets PFS, OS Endpoints in Phase III Advanced Melanoma Trial

A phase III study investigating Keytruda patients with advanced melanoma met two primary endpoints, demonstrating improvements in progression-free survival and overall survival compared to Yervoy. The study’s independent data monitoring committee recommended stopping the trial early.

In the trial, named KEYNOTE-006, Keytruda (pembrolizumab) improved PFS by 42 percent and extended overall survival by 34 percent compared to Yervoy (ipilimumab).

Investigators from 16 countries enrolled 834 patients with metastatic melanoma in the clinical trial, and patients were randomly assigned to Keytruda and Yervoy. The study was published online in the New England Journal of Medicine, and was presented at the annual meeting of the American Association for Cancer Research. The trial was sponsored by Merck.


Prostate Cancer

Three Xtandi Trials Show Positive Results In Castration-Resistant Prostate Cancer

Astellas Pharma Inc. and Medivation Inc. presented an updated overall survival analysis from the placebo-controlled phase III trial of Xtandi in chemotherapy-naive metastatic CRPC.

The companies also published data from two separate phase II head-to-head studies, named STRIVE and TERRAIN, comparing Xtandi (enzalutamide) to Casodex (bicalutamide).

The phase III trial, named PREVAIL, was a randomized, double-blind trial that enrolled 1,717 patients at sites in the U.S., Canada, Europe, Australia, Russia, Israel and Asia, including Japan.


Drugs and Targets

FDA Updates Zytiga Label To Include Chemotherapy-Naive Metastatic CRPC Data

FDA approved a label update for Zytiga (abiraterone acetate) plus prednisone to include overall survival results in chemotherapy-naive men with metastatic castration-resistant prostate cancer.

The update was based on the final analysis of the phase III, randomized, double-blind, placebo-controlled COU-AA-302 study, which showed that Zytiga plus prednisone significantly prolonged median overall survival, compared to placebo plus prednisone. 


Breast Cancer

Ongoing Phase II Trial Shows Correlation Between Immune Response and Recurrence



Circulating Tumor Cells Can Be Used to Detect DLBCL Recurrence, Researchers Say

 NCI CTEP-Approved Trials for the Month of April 
April 2015
March 2015PDF


Phase III Trial of Imbruvica Unblinded Following Significant Increase in PFS

An independent data monitoring committee recommended unblinding the phase III HELIOS trial, which is evaluating Imbruvica in combination with bendamustine and rituximab in patients with chronic lymphocytic leukemia or small lymphocytic lymphoma, following clinically meaningful and statistically significant treatment benefit.

The study has met its primary endpoint in extending progression-free survival. The safety profile of Imbruvica combination was consistent with prior clinical experience. Imbruvica is jointly developed and commercialized by Pharmacyclics and Janssen Biotech Inc.

HELIOS, an international, placebo-controlled trial enrolled 578 CLL or SLL patients who had received at least one line of prior systemic therapy. Patients were randomized to receive either Imbruvica orally once daily in combination with six cycles of BR; or placebo orally once daily with six cycles of BR, with treatment continuing until disease progression or unacceptable toxicity.

 Prostate Cancer

Provenge Immune Response Continued For Two Years in Phase II Study in BRPC

Preliminary results from the phase II STAND trial showed a robust immune response with Provenge (sipuleucel-T) that continued two years after completing treatment in men with biochemically-recurrent prostate cancer. 

The STAND study is a randomized trial consisting of two patient study groups. One group completed Provenge two weeks before initiation of androgen deprivation therapy and the second received Provenge three months after the start of ADT.

Preliminary results from STAND indicate that immune responses were observed in both study arms and suggest there may be a greater cellular immune response in patients who received Provenge prior to ADT compared with those who received Provenge following three months of ADT. Humoral immune responses were observed and similar between both treatment arms.

 Drugs and Targets

FDA Grants Accelerated Approval to Farydak for Patients with Multiple Myeloma

FDA granted accelerated approval to Farydak (panobinostat) for the treatment of patients with multiple myeloma.

An improvement in survival or disease-related symptoms has not yet been established for Farydak. The drug’s sponsor, Novartis Pharmaceuticals, is required to conduct confirmatory trials to verify and describe the clinical benefit of Farydak. FDA had previously granted Farydak priority review and orphan product designation.

Farydak inhibits histone deacetylases, which may slow the over-development of plasma cells in multiple myeloma patients or cause these cells to die. Farydak is the first HDAC inhibitor approved to treat multiple myeloma. 

Also: FDA approves Unituxin, the EU approves Jakavi, and more

 Soft Tissue Sarcoma
Phase III Halaven Trial Shows Extended OS over Dacarbazine
 Brain Cancer
Study Shows 73% Survival at Three Years by Combining Radiation Therapy and Chemotherapy
Pacritinib Phase II Study Shows Reduction in Spleen Volume
 NCI CTEP-Approved Trials for the Month of March
March 2015
February 2015PDF


Gazyva Increases PFS in Phase III Trial Of Indolent Non-Hodgkin’s Lymphoma Patients

Patients with indolent non-Hodgkin’s lymphoma lived significantly longer without disease worsening or death when treated with Gazyva (obinutuzumab) plus bendamustine and followed by Gazyva alone, compared to bendamustine alone. 

The phase III trial was stopped by an independent data monitoring committee following a pre-planned interim analysis due to the level of benefit seen in the Gazyva arm compared to the bendamustine arm. The study’s primary endpoint was progression-free survival. There were no unexpected adverse events with Gazyva.


Imbruvica Demonstrates 88% Response Rate In Studies of Relapsed/Refractory CLL Patients

Two independent phase III clinical trials, LUX-Lung 3 and LUX-Lung 6, in epidermal growth factor receptor mutation-positive metastatic non-small cell lung cancer demonstrated positive results in overall survival.

In each trial, patients whose tumors have the most common EGFR mutation—deletion in exon 19—lived more than one year longer when treated with first-line afatinib (Gilotrif) compared to standard chemotherapy. The data was published in The Lancet Oncology.

 Drugs and Targets

FDA Grants Accelerated Approval to Ibrance In HER2-Negative Metastatic Breast Cancer

FDA granted accelerated approval to Ibrance (palbociclib) to treat metastatic breast cancer.

Ibrance inhibits cyclin-dependent kinases 4 and 6, which are involved in promoting the growth of cancer cells. Ibrance is intended for postmenopausal women with estrogen receptor-positive, human epidermal growth factor receptor 2-negative metastatic breast cancer who have not yet received an endocrine-based therapy. It is to be used in combination with letrozole.

Also: FDA approves Lenvima, expands label for Revlimid, and more

 Prostate Cancer
Researchers: Cabazitaxel Functions Differently Than Other Taxanes
 Childhood Cancer
Cranial Irradiation Can Increase Risk of Pituitary Hormone Deficiencies Later in Life, Study Says
Study: Lymphoseek Patients Had Fewer Sentinel Lymph Nodes Removed Per Procedure
 Head and Neck Cancers
TCGA Researchers Discover Genomic Differences in Cancers Caused by Infection
 NCI CTEP-Approved Trials for the Month of February
February 2015
January 2015PDF

 Colorectal Cancer

Amgen Presents Phase II and III Vectibix Studies in Wild-Type RAS Colorectal Cancer

Amgen presented data from the phase II PEAK and phase III PRIME studies evaluating first-line use of Vectibix (panitumumab) in combination with FOLFOX chemotherapy regimen in patients with wild-type RAS metastatic colorectal cancer.

In an exploratory analysis from the phase II study, treatment with Vectibix compared to Avastin (bevacizumab) resulted in a significantly higher proportion of patients with earlier tumor shrinkage at week eight (64 percent vs. 45 percent, respectively; 95 percent CI, p=0.0232), and among responding patients, a significantly longer duration of response (11.4 vs. 8.5 months, respectively; 95% CI, p=0.0142) and greater depth of response (65 percent vs. 46 percent, respectively; p=0.0007). 

 Lung Cancer

Two Phase III LUX-Lung Trials of Gilotrif Demonstrate Benefits in Overall Survival

Two independent phase III clinical trials, LUX-Lung 3 and LUX-Lung 6, in epidermal growth factor receptor mutation-positive metastatic non-small cell lung cancer demonstrated positive results in overall survival.

In each trial, patients whose tumors have the most common EGFR mutation—deletion in exon 19—lived more than one year longer when treated with first-line afatinib (Gilotrif) compared to standard chemotherapy. The data was published in The Lancet Oncology.

 Drugs and Targets

FDA Approves Opdivo in Metastatic Melanoma

FDA approved Opdivo (nivolumab) injection for the treatment of patients with unresectable or metastatic melanoma and disease progression following Yervoy (ipilimumab) and, if BRAF V600 mutation positive, a BRAF inhibitor.

This indication was granted under an accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. Opdivo is sponsored by Bristol-Myers Squibb Company.

The efficacy of Opdivo was evaluated based on a single-arm, non-comparative planned interim analysis of the first 120 patients who received Opdivo with a minimum of six months follow-up in the phase III CheckMate-037 trial.

Also: Updated approvals for Imbruvica, Gazyva and the MarginProbe medical device

 Breast Cancer
Phase III MARIANNE Study Fails To Improve PFS with Kadcyla
 Polycythemia Vera
Jakavi Trial Shows Hematocrit Control Without Phlebotomy
CPX-351 Shows Clinical Benefit In Poor-Risk AML in Phase II
 NCI CTEP-Approved Trials for the Month of January
February 2015
December 2014PDF

 Drugs and Targets

FDA Grants Approvals to Lynparza, Blincyto, Xgeva, Gardasil 9 and Cyramza

FDA approved Lynparza (olaparib) capsules as monotherapy for the treatment of patients with deleterious or suspected deleterious germline BRCA mutated advanced ovarian cancer who have been treated with three or more prior lines of chemotherapy. FDA also approved a molecular companion diagnostic.

The approval of Lynparza, sponsored by AstraZeneca Pharmaceuticals LP, is based on objective response rate from the international single-arm trial in patients with deleterious or suspected deleterious gBRCAm advanced cancers. The trial enrolled 137 patients with measurable, gBRCAm-associated ovarian cancer treated with three or more prior lines of chemotherapy.


Tasigna Shows High Response, PFS Benefit Compared to Gleevec in Phase III CML Study

Six-year results from the randomized phase III ENESTnd study continued to show higher rates of early, deep and sustained molecular responses when using Tasigna (nilotinib) compared to Gleevec (imatinib mesylate) in newly-diagnosed Philadelphia chromosome-positive chronic myeloid leukemia. 

The data also demonstrated a reduced risk of progression compared to Gleevec. The update was presented at the annual meeting of the American Society of Hematology in San Francisco.

The difference in the rates of MR4.5 showed continued improvement for both Tasigna 300 mg and 400 mg twice-daily arms compared to Gleevec (MR4.5: 6-10 percent difference by one year, 22-23 percent difference by six years). MR4.5 represents an extremely low level of detectable BCR-ABL protein, the cause of Ph+ CML (measured in the blood at 0.0032 percent or less on a standardized international scale). 


 Breast Cancer

Ovarian Suppression Treatment Plus Tamoxifen Can Lower Recurrence Risk

Premenopausal women who received ovarian suppression treatment along with tamoxifen had a lower risk of breast cancer recurrence, according to data from a clinical trial sponsored and supported by NCI.

The study showed that suppressing ovarian function reduced breast cancer recurrence in premenopausal women receiving the drug tamoxifen after surgery for early-stage breast cancer. 

The phase III trial, SOFT (Suppression of Ovarian Function Trial), used either monthly injections of the drug triptorelin, surgical removal of both ovaries, or radiation of the ovaries as methods of ovarian suppression in women with hormone receptor-positive breast cancer. 

Phase II Imbruvica Trial Shows 47% of MCL Patients Alive at 27-Month Follow-up
 Gastric Cancer
Amgen Cancels Phase III Trials of Rilotumumab
 NCI CTEP-Approved Trials for the Month of December
January 2015
November 2014PDF


PD-1 Checkpoint Inhibitor Opdivo First to Demonstrate Survival Benefit in Phase III

A study comparing Opdivo to dacarbazine chemotherapy in treatment naïve advanced melanoma patients marks first PD-1 immune checkpoint inhibitor to demonstrate a survival benefit in a phase III trial.

The trial, CheckMate-066, met its primary endpoint of overall survival, with median OS not reached in the Opdivo (nivolumab) arm, compared to 10.8 months in patients receiving dacarbazine chemotherapy.

The one-year survival rate was 73 percent for Opdivo vs. 42 percent for DTIC, and there was a 58 percent decrease in the risk of death for patients treated with Opdivo (HR: 0.42, p<0.0001).


 Ovarian Cancer

Phase III Trebananib Trial Fails OS Endpoint In Recurrent Platinum-Resistant Ovarian Cancer

Top-line secondary endpoint results from the phase III TRINOVA-1 trial in women with recurrent platinum-resistant ovarian cancer did not demonstrate a statistically significant improvement in overall survival. The study evaluated trebananib plus paclitaxel versus placebo plus paclitaxel.

Median overall survival was 19.3 months in the trebananib arm versus 18.3 months in the control arm. The data will be submitted to a future medical conference and for publication according to Amgen, trebananib’s sponsor.

In the previously reported primary endpoint analysis, the data demonstrated a statistically significant difference in progression-free survival for trebananib. In that analysis, patients treated with trebananib showed a 34 percent reduction in the risk of disease progression or death (HR = 0.66, 95 percent CI, 0.57, 0.77, p<0.001). The median progression-free survival was 7.2 months in the trebananib arm versus 5.4 months in the control arm.


Phase III Tumor Treating Fields Trial Halted Following Positive Results in Interim Analysis

A phase III trial of Tumor Treating Fields was terminated early following early success detailed in an interim analysis. The trial evaluated patients with newly diagnosed glioblastoma being treated with the NovoTTF-100A System, developed by Novocure, in combination with standard-of-care temozolomide.

The treatment extended both progression-free survival and overall survival compared to temozolomide alone. The trial’s independent data monitoring committee recommended terminating the trial early and allowing all control patients to cross over to the treatment arm.

 Non-Small Cell Lung Cancer

 Prostate Cancer
Galeterone Shows Potential In CRPC AR Variants, Study Says
 NCI CTEP-Approved Trials for the Month of November
 FDA News

  • Cyramza approved in advanced gastric cancer

  • Lymphoseek indication expanded to include mapping in solid tumors

  • Fast Track designation granted to MM-398 adenocarcinoma of the pancreas

  • Orphan Drug designation granted to JCAR015 in ALL

  • FDA taking public comment on “first generic” ANDA processes

December 2014
Page 3 of 41234