November 2016PDF

 

Guidelines

New Evidence-Based Guideline on HER2 Testing for Patients with Gastric Cancer

The College of American Pathologists, the American Society for Clinical Pathology, and the American Society of Clinical Oncology released an evidence-based clinical practice guideline on human epidermal growth factor receptor 2 testing for patients with gastroesophageal cancers.

 

Urothelial Cancer

Phase III Keytruda Study Shows Better OS vs. Chemo for Advanced Urothelial Cancer

Merck announced that the phase III KEYNOTE-045 trial investigating the use of Keytruda (pembrolizumab), the company’s anti-PD-1 therapy, in patients with previously treated advanced urothelial cancer, met the primary endpoint of overall survival.

 

Regulatory Actions

FDA Approves New Indications for Darzalex, Keytruda, Opdivo

Janssen Biotech said FDA approved Nov. 21 daratumumab (Darzalex) in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of patients with multiple myeloma who have received at least one prior therapy.

 

Multiple Myeloma

Study met Primary Endpoint of Non-Inferiority Versus Zoledronic Acid in Delaying Skeletal-Related Events

Amgen announced that a phase III study evaluating XGEVA (denosumab) versus zoledronic acid met the primary endpoint of non-inferiority (hazard ratio = 0.98, 95 percent CI, 0.85 – 1.14) in delaying the time to first on-study skeletal-related event in patients with multiple myeloma.

 

Prostate Cancer

 

Testicular Cancer

High-Dose Chemo and Stem Cell Transplant Cures Most Relapsed Testis Cancer

 

Bladder Cancer

Positive Survival Results from Apatorsen Phase II Trial in Metastatic Bladder Cancer

 

Melanoma

 

Immunotherapy

Nektar Phase II Study: Anti-tumor activity in 7/18 evaluable patients with solid tumors

 

NCI CTEP-Approved Trials for November

November 2016
October 2016PDF

 

 

Non-Small Cell Lung Cancer

Phase III Tecentriq Study Shows Better Survival vs. Chemo Regardless of PD-L1 Status

Genentech said its pivotal phase III OAK study of Tecentriq (atezolizumab) showed a median survival of 13.8 months, 4.2 months longer than those treated with docetaxel chemotherapy (median overall survival [OS]: 13.8 vs. 9.6 months; HR = 0.73, 95% CI: 0.62 – 0.87).

The results were presented at the European Society of Medical Oncology 2016 Annual Meeting in Copenhagen.

The OAK study evaluated people with non-small cell lung cancer whose disease had progressed on or after treatment with one or more platinum-based chemotherapy (second-line and third-line).

 

Melanoma

Yervoy Improved OS in Fully Resected Stage III Patients from Phase III Study

Bristol-Myers Squibb Co. announced superior efficacy for Yervoy 10 mg/kg versus placebo on all survival endpoints in the phase III trial CA184-029 (EORTC 18071) evaluating stage III melanoma patients who are at high risk of recurrence following complete surgical resection.

In the study, Yervoy compared with placebo significantly improved overall survival (OS) (HR=0.72 [95.1% CI: 0.58-0.88; p=0.001]), a secondary endpoint, with five-year OS rates at 65.4% in the Yervoy group and 54.4% in the placebo group.

 

Head and Neck Carcinoma

Opdivo Stabilized Patient-Reported Outcomes in Phase III Study

Bristol-Myers Squibb Co. announced patient-reported quality-of-life data from an exploratory endpoint in the pivotal phase III CheckMate -141 trial evaluating Opdivo in patients with recurrent or metastatic squamous cell carcinoma of the head and neck after platinum therapy compared to investigator’s choice of therapy (methotrexate, docetaxel or cetuximab).

Outcome assessments showed Opdivo stabilized patients’ symptoms and functioning, including physical, role and social functioning across three separate instruments, the company said.

Both PD-L1 expressors and non-expressors treated with investigator’s choice of therapy experienced statistically significant worsening of patient-reported outcomes from baseline to week 15 versus Opdivo.

 

Bladder Cancer

Phase III Trial Confirms ORR in Previously Treated Patients who Received Opdivo

 

Renal Cell Carcinoma

Durable Responses Seen With Opdivo and Yervoy in Updated Analysis

 

Colorectal Cancer

 

Breast Cancer

Novartis’s LEE011 + Letrozole Shows Superior PFS as First-Line Treatment for HR+/HER2- Advanced Breast Cancer

 

Pancreatic Cancer

ONIVYDE Regimen Produced OS, PFS Benefit In Metastatic Disease

 

Multiple Myeloma

Kyprolis Study in Newly Diagnosed Disease Doesn’t Meet Primary Endpoint—PFS

 

Retinoblastoma

Triple-drug Chemo with Topotecan Helps Preserve Vision in Patients

 

NCI CTEP-Approved Trials For the Month of October

 

Regulatory Actions

  • Genentech receives second Breakthrough Therapy Designation from FDA for Alecensa
  • Gamida Cell granted Breakthrough Therapy Designation for NiCord
  • Janssen Research & Development submits supplemental NDA for ibrutinib
  • European Medicines Agency recommends conditional marketing authorization for olaratumab in combination with doxorubicin
  • FDA accepts Array Biopharma’s NDA for binimetinib
October 2016
13380
August/September 2016PDF

 

 

Non-Small Cell Lung Cancer

Tecentriq Demonstrates Increase In Overall NSCLC Survival in Phase III Study

Genentech announced positive results for Tecentriq (atezolizumab) from the Phase III study OAK. The study met its co-primary endpoints and showed a statistically significant and clinically meaningful improvement in overall survival compared with docetaxel chemotherapy in people with locally advanced or metastatic non-small cell lung cancer whose disease progressed on or after treatment with platinum-based chemotherapy.

Adverse events were consistent with what has been previously observed for Tecentriq. Genentech, a member of the Roche Group, will present full results at an upcoming medical meeting in 2016.

Also:

 

Lymphoma

Adcetris Improves ORR4 in Phase III Trial

Takeda Pharmaceutical Co. Ltd. and Seattle Genetics Inc. said that the phase III ALCANZA clinical trial evaluating Adcetris (brentuximab vedotin) in cutaneous T-cell lymphoma met its primary endpoint, demonstrating a highly statistically significant improvement in the rate of objective response lasting at least four months (ORR4).

This randomized trial, which received a Special Protocol Assessment from FDA and scientific advice from the European Medicines Agency, compared the use of single-agent Adcetris to a control arm of investigator’s choice of standard therapies, methotrexate or bexarotene, in 131 patients with CD30-expressing CTCL who received prior systemic or radiation therapy.

 

Breast Cancer

Abemaciclib Phase III Trial Continues After Interim Efficacy Criteria Not Met

Eli Lilly and Co. said that following a pre-planned interim analysis of the MONARCH 2 trial, an independent data monitoring committee provided the recommendation to continue the study without modification as the interim efficacy criteria were not met.

The phase III trial compares abemaciclib plus fulvestrant versus placebo with fulvestrant in women with hormone-receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) locally advanced or metastatic breast cancer.

 

Prostate Cancer

Custirsen Trial Fails to Show Improvement in Survival

 

Melanoma

Two-drug Immunotherapy May Produce Better Survival in Advanced Melanoma

 

Hepatocellular Carcinoma

Study Confirms Association Between RFA Burn Time, OS In Patients Receiving ThermoDox

 

Kidney Cancer

Study Finds HIF-2 Inhibitors More Effective Than Sunitinib

 

Regulatory Actions

Novartis, MEI Pharma. Receive Breakthrough Therapy Designations

 

NCI CTEP-Approved Trials for the Months of August and September

 

Screening

FDA Warns Against Ovarian Cancer Screening

September 2016
July 2016PDF

 

 

Ovarian Cancer

Niraparib Demonstrates Prolonged PFS in Phase III Trial,
Achieving Primary Endpoint

Niraparib achieved its primary endpoint in a phase III ovarian cancer trial, demonstrating prolonged progression-free survival compared to placebo among patients who are germline BRCA mutation carriers; among patients who are not germline BRCA mutation carriers, but who have homologous recombination deficient tumors as determined by the Myriad myChoice HRD test; and overall in patients who are not germline BRCA mutation carriers.

The trial, NOVA, is a double-blind, international trial that enrolled more than 500 patients with recurrent ovarian cancer who were in a response to their most recent platinum-based chemotherapy. There is currently no therapy approved by FDA for maintenance treatment of patients with recurrent ovarian cancer following response to platinum, according to Tesaro Inc., niraparib’s sponsor. Niraparib is an oral, once-daily PARP inhibitor.

 

Breast Cancer

Phase III Trial Rules Out Inferiority of
Trastuzumab Biosimilar ABP 980

Amgen and Allergan plc announced results from a phase III study evaluating efficacy and safety of biosimilar ABP 980 compared with trastuzumab in patients with human epidermal growth factor receptor 2-positive early breast cancer.

ABP 980 is being developed as a biosimilar to trastuzumab, a recombinant DNA-derived humanized monoclonal immunoglobulin G1 kappa antibody which targets HER2. The active ingredient of ABP 980 is a humanized monoclonal antibody that has the same amino acid sequence as trastuzumab. ABP 980 has the same pharmaceutical dosage form and strength as trastuzumab in the U.S. and the European Union.

 

Drugs and Targets

 

Colorectal Cancer

 

Lymphoma

 

NCI CTEP-Approved Trials For the Month of July

August 2016
June 2016PDF

 

 

Leukemia and Lymphoma

Three Phase III Studies of Imbruvica Presented at ASCO Annual Meeting

AbbVie published longer-term follow-up results from three phase III studies of Imbruvica (ibrutinib) in chronic lymphocytic leukemia and small lymphocytic lymphoma: RESONATE, RESONATE-2 and HELIOS.

These data were presented at the annual meeting of the American Society of Clinical Oncology. Imbruvica is jointly developed and commercialized in the U.S. by Pharmacyclics LLC, an AbbVie company, and Janssen Biotech Inc.

“Our clinical data presented at this year’s ASCO from several randomized studies demonstrate solid durability of response with Imbruvica in patients with CLL/SLL with additional follow-up of up to three years,” said Danelle James, head of oncology at Pharmacyclics.

Also:

 

Breast Cancer

Combination of Surgery and Standard Therapy Increases Survival in Stage IV, Study Says

A combination of surgery to remove the primary tumor in women diagnosed with stage IV breast cancer, followed by standard therapies, can add months to patients’ lives when compared with standard therapy alone, according to an international phase III study.

“Our findings will change the standard of care for women newly diagnosed with stage IV breast cancer,” said lead investigator Atilla Soran, clinical professor of surgery at the University of Pittsburgh School of Medicine and breast surgical oncologist with UPMC CancerCenter. “We’ve shown that surgery to remove the primary tumor—either through lumpectomy or mastectomy—followed by standard therapy, is beneficial over no surgery.”

Also:

 

Drugs and Targets

FDA Approves EGFR Companion Diagnostic For Tarceva Therapy

 

Melanoma

 

Soft Tissue Sarcoma

Phase III Eribulin Trial Boosts OS in Liposarcoma Patients

 

Multiple Myeloma

Kyprolis, Lenalidomide and Dexamethasone Combination Improves PFS, OS in Phase III

 

NCI CTEP-Approved Trials for the Month of June

June 2016
May 2016PDF

 

 Multiple Myeloma

Study: Combination of ASCT and Bortezomib
Can Increase Survival

Early findings from a phase III clinical trial showed that patients with multiple myeloma who received an autologous stem cell transplant survived longer without disease progression than those who received only chemotherapy using novel agents.

The study was the largest reported aimed at comparing ASCT with a bortezomib-based regimen alone in patients younger than 65, and will be presented at this year’s annual meeting of the American Society of Clinical Oncology, June 3-7 in Chicago.

“Even in an age of novel therapies, proven approaches can retain their value. This study demonstrated that combining the best of both worlds—initial therapy with a novel agent followed by stem cell transplant—resulted in the best patient outcomes,” said ASCO President Julie Vose in a statement.

 Colorectal Cancer

Cancers Originating on Left Side of Colon
Associated with Longer Survival, Study Says

A retrospective analysis found that the location of the primary tumor within the colon predicts survival and may help inform optimal treatment selection for patients with metastatic colorectal cancer.

The data show that patients whose primary tumors originate on the left side of the colon—including the descending colon, sigmoid colon and rectum—survive significantly longer than those whose tumors originate on the right side, or the cecum and ascending colon.

Researchers retrospectively evaluated data from the phase III CALGB/SWOG 80405 clinical trial, a federally funded clinical trial designed to compare Avastin (bevacizumab) and Erbitux (cetuximab) in combination with chemotherapy as initial therapy for metastatic colorectal cancer.

 Drugs and Targets

FDA Approves Tecentriq, Opdivo, Imbruvica and Lenvima

FDA granted accelerated approval to Tecentriq (atezolizumab) for urothelial carcinoma, the most common type of bladder cancer. This is the first product in its class of PD-1/PD-L1 inhibitors approved to treat this type of cancer, according to the drug’s sponsor, Genentech.

Tecentriq is approved for the treatment of patients with locally advanced or metastatic urothelial carcinoma whose disease has worsened during or following platinum-containing chemotherapy, or within 12 months of receiving platinum-containing chemotherapy, either before or after surgical treatment.

Also:

Non-Small Cell Lung Cancer

 Melanoma

Phase Ib Trial Shows 40 Percent of Patients
Receiving Keytruda Alive After 36-Month Follow Up

 

Mesothelioma

WT1 Vaccine Doubles PFS in Phase II Trial

 

Breast Cancer

LEE011 Meets Primary Endpoint, Improves PFS
in Phase III Trial

 

Precision Medicine

Study: Precision Medicine Yields Better
Outcomes in Phase I Clinical Trials

 

Palliative Care

Study: Early Palliative Care Provides Benefits
for Family Caregivers of Patients

 

NCI CTEP-Approved Trials for the Month of May
June 2016
April 2016PDF

 

Head and Neck Cancers

Opdivo Extends OS in Phase III Squamous Cell Carcinoma Trial

A phase III trial of PD-1 inhibitor Opdivo showed significant survival benefit at one year—compared to investigator’s choice of methotrexate, docetaxel or cetuximab—in patients with recurrent or metastatic squamous cell carcinoma of the head and neck.

Patients treated with Opdivo (nivolumab) experienced a 30 percent reduction in the risk of death, with a median overall survival of 7.5 months (95% CI: 5.5-9.1) compared to 5.1 months (95% CI: 4.0-6.0) for investigator’s choice (HR=0.70 [97.73% CI: 0.51-0.96] p=0.0101).

The one-year survival rate for Opdivo was 36 percent compared to 16.6 percent for investigator’s choice. The safety profile of Opdivo in CheckMate-141 was consistent with prior studies, with no new safety signals identified.

     

    Melanoma

    Opdivo-Yervoy Combination Demonstrates Two-Year Survival Rate of 69 Percent

    Overall survival data from CheckMate-069, a phase II trial of a Opdivo and Yervoy combination regimen in patients with previously untreated advanced melanoma, demonstrated a two-year overall survival rate of 69 percent compared to 53 percent for Yervoy alone (HR=0.58 [95% CI: 0.31-1.08]) in patients with BRAF wild-type advanced melanoma.

    CheckMate-069 evaluated 142 patients with previously untreated unresectable or metastatic melanoma who received either the Opdivo and Yervoy combination regimen (n=95) or Yervoy alone (n=47). The trial included patients with BRAF wild-type and BRAF V600 mutation-positive melanoma, and randomization was stratified by BRAF mutation status.

       

      Drugs and Targets

      FDA Grants Accelerated Approval To Venclexta Tablets in CLL

      FDA granted accelerated approval to Venclexta tablets (venetoclax) for patients diagnosed with chronic lymphocytic leukemia with 17p deletion, as detected by an FDA-approved test, who have received at least one prior therapy.

      The indication was approved based on overall response rate, and continued approval may be contingent upon verification and description of clinical benefit in a confirmatory trial.

      Also:

         

        Ovarian Cancer

         

        Prostate Cancer

        Study: SBRT Delivers 98.6% Cure Rate at Five-Year Followup

         

        Soft Tissue Sarcoma

        Researchers: Radiation After Surgery Benefits Older Patients More than Younger Patients

         

        NCI CTEP-Approved Trials for the Month of April

         

        Letter to the Editor

        GOG Foundation Sends Rebuttal Letter to Oncolytics Biotech

        May 2016
        March 2016PDF

         

         

        Leukemia

        Vyxeos Injection Improves Overall Survival In Phase III Acute Myeloid Leukemia Trial

        A phase III trial of Vyxeos Liposome for Injection demonstrated statistically significant improvements in overall survival in patients with high-risk secondary acute myeloid leukemia.

        The median overall survival for patients treated with Vyxeos (cytarabine: daunorubicin) in the study was 9.56 months compared to 5.95 months for patients receiving the standard of care regimen of cytarabine and daunorubicin known as 7+3.

        The hazard ratio was 0.69 (p=0.005) which represents a 31 percent reduction in the risk of death versus 7+3, according to Celator Pharmaceuticals Inc., the drug’s sponsor, which plans to submit the data for presentation at the 2016 annual meeting of the American Society of Clinical Oncology.

         Non-Small Cell Lung Cancer

        Atezolizumab Immunotherapy Boosts OS Compared to Docetaxel in Phase II Trial

        Patients with advanced metastatic lung cancer treated with atezolizumab, a targeted immunotherapy drug, lived significantly longer and with fewer side effects than those who received docetaxel chemotherapy, according to a study published in The Lancet.

        “The results of this study demonstrate that the use of atezolizumab, a monoclonal antibody, improves the survival rate of a majority of lung cancer patients who have progressive cancer when used after first-line chemotherapy,”

        Also:

         Drugs and Targets

        FDA Approves Imbruvica in First-Line CLL

        FDA approved Imbruvica (ibrutinib) as a first-line treatment for patients with chronic lymphocytic leukemia.

        The approval is based on data from the randomized, multi-center, open-label phase III RESONATE-2 trial, which evaluated the use of Imbruvica versus chlorambucil in 269 treatment-naïve patients with CLL or small lymphocytic lymphoma aged 65 years or older. The data were previously presented at the annual meeting of the American Society of Hematology in December 2015 and also published in The New England Journal of Medicine.

        Also:

        Ovarian Cancer

        Study: Reolysin-Paclitaxel Combination Demonstrates Higher Response Than Paclitaxel Therapy Alone

         Glioblastoma

        Tocagen Expands Phase II/III Trial, Begins Enrolling in Canada

         Cachexia

        Two Phase III Anamorelin Trials Show Improved Lean Body Mass

         NCI CTEP-Approved Trials for the Month of March
        March 2016
        February 2016PDF

         

        Leukemia

        Phase III Blincyto Study Stopped Early After Meeting OS Primary Endpoint

        A phase III study of Blincyto met its primary endpoint of overall survival in patients with acute lymphoblastic leukemia following a prespecified interim analysis. The study was stopped early.

        The randomized, open-label TOWER study evaluated the efficacy of Blincyto (blinatumomab) versus the standard of care in adult patients with Philadelphia chromosome-negative relapsed or refractory B-cell precursor acute lymphoblastic leukemia.

        Patients were randomized in a 2:1 ratio to receive Blincyto or treatment with investigator choice of one of four protocol defined SOC chemotherapy regimens.

           

          Soft Tissue Sarcoma

          Halaven Study Improves Overall Survival In Liposarcomas and Leiomyosarcomas

          Full results from a phase III study showed improved median overall survival in unresectable locally advanced liposarcomas and leiomyosarcomas in patients receiving Halaven (eribulin), compared to dacarbazine.

          The clinical trial, study 309, included data from 452 adults, and was published in The Lancet, which also published an editorial discussing the study results.

          The study compared patients treated with eribulin mesilate (1.4 mg/msquared intravenously on days 1 and 8) and those treated with dacarbazine (850 mg/msquared, 1000 mg/msquared, or 1200 mg/msquared [dose dependent on center and clinician] intravenously on day 1). Additional endpoints included progression-free survival and quality of life.

             

            Breast Cancer

            OBI-822/821 Phase II/III Study Does Not Meet PFS Endpoint, But Shows Positive Results In Patients with Immune Response

            OBI Pharma Inc., announced topline results from a phase II/III study of OBI-822/821 (formerly OPT822/OPT821), which evaluated the clinical benefit and immunogenicity in patients with metastatic breast cancer. The study did not meet the primary efficacy endpoint of progression-free survival.

            However, patients who demonstrated an immune response showed highly significant improvement in progression-free survival and the secondary endpoint of overall survival is trending towards statistical significance. OBI-822/821 was generally well tolerated with no major safety concerns. Full results will be presented at an upcoming international scientific conference.

               

              Pancreatic Cancer

              Two Studies Evaluate 2nd Line Treatments Following Abraxane

               

              Non-Small Cell Lung Cancer

              Gilotrif Improves PFS Compared to Iressa in Phase IIb Trial

               

              Thyroid Cancer

              Study: Afirma Genomic Test Can Reduce Unnecessary Fine Needle Aspiration Biopsies

               

              NCI CTEP-Approved Trials for the Month of February

               

              Drugs and Targets

              • Gazyva Combination Approved In Follicular Lymphoma
              • FDA approves Afinitor for GI and lung NETs
              • Venetoclax receives third FDA Breakthrough Designation
              • FDA grants breakthrough designation to PKC412 (midostaurin)
              • FDA grants orphan drug designation to tazemetostat for malignant rhabdoid tumors
              • FDA grants orphan drug designation to CD101 IV for candidema
              February 2016
              January 2016PDF

               

              Melanoma

              Phase III Trial Binimetinib Increases PFS in NRAS-Mutant Melanoma vs. Dacarbazine

              Array BioPharma reported top-line results from the ongoing phase III clinical trial of binimetinib in patients with advanced NRAS-mutant melanoma, demonstrating that the study met its primary endpoint of improving progression-free survival when compared with dacarbazine treatment.

              The median PFS on the binimetinib arm was 2.8 months versus 1.5 months on the dacarbazine arm (HR=0.62, 95% CI 0.47-0.80, p < 0.001). Binimetinib was generally well-tolerated and the adverse events reported were consistent with previous results in NRAS melanoma patients. Binimetinib is a small molecule MEK inhibitor which targets key enzymes in the RAS/RAF/MEK/ERK pathway.

              Breast Cancer

              Survey of Breast Cancer Cell Function Identifies New Drug Uses, Combinations

              Researchers conducted a large analysis of breast cancer cell function, saying the results suggest dozens of new uses for existing drugs, new drug discovery targets, and new drug combinations.

              “This study represents the largest survey yet of how the genetic changes in breast cancer cells interfere with pathways critical to their growth and survival, pathways that might be targeted by combinations of new or existing drugs,” said lead study author Benjamin Neel, director of the Perlmutter Cancer Center at NYU Langone Medical Center.

              The study results were published in the journal Cell. The researchers combined genetic analyses of more breast cancer cell types than studied previously, new statistical methods, and comparisons with databases of molecular signatures and the effects of anti-cancer drugs.

              Ovarian Cancer

              Trial of 200,000 Women Shows Screening Can Reduce Mortality by 20 Percent

              One of the largest randomized trials ever has concluded that ovarian cancer screening may reduce ovarian cancer mortality by an estimated 20 percent after follow up of up to 14 years, but researchers say longer follow-up is needed to determine the ultimate mortality reduction and if screening the general population is cost effective.

              The United Kingdom Collaborative Trial of Ovarian Cancer Screening enrolled 202,638 women, aged 50-74 years, between 2001 and 2005 through 13 trial centers in England, Northern Ireland and Wales. The study results were published in The Lancet.

              The study tested the hypothesis that screening for ovarian cancer in the general population can reduce disease mortality without significant harm, in line with screening programs for other cancers.

              Colorectal Cancer

              Cervical Cancer

              Analysis Evaluates Moore Criteria for Bevacizumab Effectiveness

              NCI CTEP-Approved Trials for the Month of January
              Drugs and Targets

              • Opdivo-Yervoy combination granted accelerated approval in metastatic melanoma
              • Halaven approved for unresectable or metastatic liposarcoma
              • Zepatier approved for chronic hepatitis C
              • Health Canada grants conditional approval to Blincyto in Ph- acute lymphoblastic leukemia
              • FDA grants breakthrough designations to BI1482694 (HM61713) and venetoclax
              • Priority review granted to lenvatinib in renal cell carcinoma
              February 2016
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