NuCana announced combined results from cohorts one and two of the ABC-08 study at the European Society for Medical Oncology Congress 2018 in Munich, Germany. In this Phase Ib multi-center, open-label study in front-line treatment of patients with advanced biliary tract cancer, Acelarin combined with cisplatin was observed to continue to achieve approximately a doubling of the response rate expected with the standard of care, gemcitabine plus cisplatin. In addition, results showed the combination was well-tolerated and several patients achieved significant reductions in their tumor volume as well as further tumor shrinkage over time. Fourteen patients with advanced/metastatic biliary tract cancer received Acelarin and cisplatin on days one and eight of a three-week cycle. In the intent-to-treat group of patients, a Complete Radiological Response was achieved in one patient and a Partial Response in six patients, resulting in an Objective Response Rate of 50%. In the eleven Efficacy Evaluable patients, an Objective Response Rate of 64% was achieved. Additionally, the combination of Acelarin and cisplatin was well-tolerated over multiple cycles with no unexpected adverse events, no dose-limiting toxicities, no discontinuations due to Acelarin-associated toxicity and no Grade 4 adverse events. Based on these data from the ABC-08 study and discussions with the U.S. Food and Drug Administration, NuCana anticipates initiating a global randomized Phase III clinical study comparing Acelarin and cisplatin with gemcitabine and cisplatin in patients with front-line advanced biliary tract cancer.

Incyte announced updated data from its ongoing Phase 2 FIGHT-202 trial evaluating pemigatinib, its selective fibroblast growth factor receptor inhibitor, in patients with advanced/metastatic or surgically unresectable cholangiocarcinoma who failed at least one previous treatment. In patients with FGFR2 translocations who were followed for at least eight months, interim study results demonstrated an overall response rate of 40%, the primary endpoint, and a median progression free survival of 9.2 months, a key secondary endpoint. Pemigatinib was well-tolerated. The most common treatment-emergent adverse events were hyperphosphatemia, alopecia, diarrhea, decreased appetite and fatigue. Five patients had TEAEs with a fatal outcome, none of which were related to study treatment.

Loxo Oncology (LOXO) announced updated clinical data for larotrectinib, an investigational oral, selective, and CNS-active TRK inhibitor, in adult and pediatric patients with TRK fusion cancers. The update included approximately one year of additional follow-up for the 55 patients described in the larotrectinib New England Journal of Medicine publication from February 2018. In addition, the update included data for an additional 67 patients who were subsequently enrolled across the larotrectinib development program. As of a data cut-off date of July 30, 2018, median duration of response had not been reached in either dataset. Loxo Oncology and Bayer (BAYRY) are engaged in a collaboration for the development and commercialization of larotrectinib. The U.S. Food and Drug Administration has accepted the New Drug Application submitted by Loxo Oncology, and granted Priority Review for larotrectinib for the treatment of adult and pediatric patients with locally advanced or metastatic solid tumors harboring a neurotrophic tyrosine receptor kinase gene fusion. The FDA has set a target action date of November 26, 2018, under the Prescription Drug User Fee Act. Bayer has submitted a Marketing Authorization Application in the EU and additional filings in other markets are underway. Larotrectinib was well tolerated, with the majority of adverse events recorded as grade 1 or 2. No treatment-related grade 3 or 4 adverse events occurred in more than 5% of patients. Eleven patients required larotrectinib dose reductions. In all cases, patients whose doses were reduced maintained their best response at the lower dose. One patient discontinued larotrectinib due to an adverse event.

Genentech, a member of the Roche, announced results from an integrated analysis of the pivotal Phase II STARTRK-2, Phase I STARTRK-1 and Phase I ALKA-372-001 trials that showed the investigational personalized medicine entrectinib shrank tumors in more than half of people with neurotrophic tropomyosin receptor kinase fusion-positive solid tumors. Objective responses to entrectinib were seen across 10 different solid tumor types, including in people with and without central nervous system metastases at baseline. Importantly, entrectinib shrank tumors that had spread to the brain in over half of people, with more than a quarter of these people having a complete response. The safety profile of entrectinib was consistent with that seen in previous analyses. Entrectinib has been granted Breakthrough Therapy Designation by the U.S. Food and Drug Administration for the treatment of NTRK fusion-positive, locally advanced or metastatic solid tumors in adult and pediatric patients who have either progressed following prior therapies or have no acceptable standard therapies. Breakthrough Therapy Designation is designed to expedite the development and review of medicines intended to treat serious or life-threatening diseases and to help ensure people have access to them through FDA approval as soon as possible. Genentech plans to submit results from these integrated analyses to global health authorities for the treatment of NTRK fusion-positive solid tumors and ROS1-positive NSCLC.

BioLineRx (BLRX) disclosed additional data from the in-depth analyses of biopsies of the dual combination arm of the Phase 2a COMBAT/KEYNOTE-202 study, evaluating patients with metastatic pancreatic adenocarcinoma treated with BL-8040 in combination with Keytruda, an anti-PD-1 therapy marketed by Merck (MRK). The results presented demonstrate that BL-8040 significantly improves T-cell infiltration into the tumor and reduces immunosuppression in the tumor microenvironment. The study included 37 patients with metastatic PDAC who had disease progression after one or more previous lines of treatment. Study treatment consisted of an initial 5-day priming period of BL-8040 monotherapy, followed by repeated 3-week cycles of BL-8040 in combination with Keytruda. In addition to clinical efficacy assessments, the study included a number of pharmacodynamic assessments to support BL-8040's mechanism of action as an immuno-oncology agent. The additional data from in-depth analyses of biopsies taken at screening and following monotherapy or combination treatment of BL-8040 and Keytruda demonstrate that in 75% of the available biopsies, BL-8040 treatment promotes an increase in the number of infiltrating CD4+, CD8+ and CD8+Granzyme B+ cytotoxic T-cells. The greatest improvement in T-cell infiltration was observed following combination treatment of BL-8040 and Keytruda and was correlated with stable disease for 8 cycles of treatment. Furthermore, increased infiltration of activated CD4 and CD8 T-cells was accompanied by a pronounced decrease in the number of tumor cells, as well as by a decrease in myeloid-derived suppressor cells, a cell type known to impede the anti-tumor immune response.

Genentech, a member of the Roche, announced positive results from the Phase III IMpassion130 study of Tecentriq plus chemotherapy - Abraxane - for the initial treatment of unresectable locally advanced or metastatic triple-negative breast cancer. The Tecentriq and chemotherapy combination significantly reduced the risk of disease worsening or death compared with chemotherapy alone in all randomized patients and the PD-L1-positive population, a subgroup determined by PD-L1 biomarker testing. At this interim analysis, statistical significance was not met for overall survival in the ITT population, but showed a clinically meaningful 9.5-month OS improvement in the PD-L1-positive population. Due to the hierarchical statistical design, results in the PD-L1-positive population were not formally tested. Follow-up will continue until the next planned analysis. Safety in the Tecentriq plus nab-paclitaxel arm appeared consistent with the known safety profiles of the individual medicines, and no new safety signals were identified with the combination.

Merck announced the first presentation of preliminary data from a Phase 1 clinical trial evaluating MK-1454, an investigational STING agonist, as monotherapy and in combination with Keytruda, Merck's anti-PD-1 therapy, in patients with advanced solid tumors or lymphomas. MK-1454 is one of more than 20 novel investigational immuno-therapeutic candidates Merck is evaluating as part of its broad oncology pipeline. In this Phase 1, open-label, multi-arm, multicenter, dose-escalation clinical trial, MK-1454 was administered to patients with advanced solid tumors or lymphomas by intratumoral injection every week for nine weeks for three cycles then every three weeks thereafter. Dose escalations for MK-1454 were 10-3,000 microg and 90-2,000 microg using accelerated titration followed by modified toxicity probability interval design. Keytruda was administered as an intravenous injection at a dose of 200 mg every three weeks. Patients receiving MK-1454 as monotherapy who progressed while on therapy were eligible for crossover to the MK-1454-Keytruda combination arm. Study objectives included evaluation of safety, tolerability, pharmacodynamics, pharmacokinetics and tumor responses evaluated using RECIST v1.1 criteria. Interim data presented at ESMO were based on findings from 26 patients enrolled in the MK-1454 monotherapy arm and 25 patients enrolled in the combination arm with Keytruda, plus 9 patients who crossed over from monotherapy to receive the combination regimen. In the monotherapy arm, no complete or partial responses were observed. In the combination arm, partial responses were observed in 24% of patients, with median reductions of 83% in the size of both target-injected and non-injected tumors. At the time of analysis, all of the partial responses were ongoing and had lasted six months or longer. None of the responders had previously received a PD-1/PD-L1 inhibitor therapy. The disease control rates were 20% and 48% for the monotherapy and combination arms, respectively. Treatment-related adverse events occurred in 82.6% and 82.1% of patients in monotherapy and combination arms, respectively. TRAEs resulting in trial discontinuation occurred in 7.1% of patients in the combination arm. No TRAE discontinuations were recorded in patients in the monotherapy arm.

Exelixis announced results from two analyses evaluating the effect of PD-L1 expression or prior treatment with immune checkpoint inhibitors on the efficacy of cabozantinib in patients with advanced renal cell carcinoma. An analysis of data from the CABOSUN and METEOR trials demonstrated that cabozantinib improved clinical outcomes regardless of PD-L1 status in patients with advanced RCC, relative to sunitinib or everolimus, the respective comparator arms for each trial. Tumor tissue from 110 patients in the CABOSUN trial and 306 patients in the METEOR trial were evaluated to determine whether PD-L1 expression predicted outcomes or response to treatment. The findings showed that PD-L1 expression was associated with shorter median progression-free survival and overall survival in both METEOR and CABOSUN. Treatment with cabozantinib, however, improved PFS and OS compared with everolimus and sunitinib in both PD-L1 positive and PD-L1 negative patients. An additional analysis evaluating the activity of cabozantinib in 69 patients with advanced RCC who progressed on immune checkpoint inhibitors found that cabozantinib was active in patients previously treated with immune checkpoint inhibitors, either alone or in combination with anti-VEGF or other therapies. At a median follow-up of 12 months, objective response rate was 33%, disease control rate was 79 percent and the one-year overall survival rate was 53%.

OncoMed Pharmaceuticals announced interim results from its ongoing Phase 1b trial investigating navicixizumab, OncoMed's anti-DLL4/VEGF bispecific antibody, in combination with paclitaxel in patients with platinum-resistant ovarian cancer. The patients had received a median of four prior therapies, all of whom had received prior paclitaxel and 69% had received prior bevacizumab. 22 of the 26 patients treated with the novel regimen experienced clinical benefit. Notably 11 of the 26 patients achieved a partial response and the median progression-free survival was 5.4 months. Historical response rates for patients with heavily pretreated platinum-resistant ovarian cancer treated with chemotherapy are typically 15% or less. The ongoing Phase 1b multicenter, open-label, dose-escalation and expansion trial is designed to assess the safety, preliminary efficacy, immunogenicity, pharmacokinetics and biomarker effects of navicixizumab plus paclitaxel. The trial has been expanded to enroll up to 60 patients with platinum-resistant ovarian cancer who have previously received bevacizumab and/or have failed at least two prior therapies.

Bristol-Myers Squibb announced follow-up data evaluating Opdivo monotherapy and Opdivo in combination with Yervoy in patients with platinum-pretreated metastatic urothelial carcinoma. Results from the Phase 1/2 CheckMate -032 trial showed that patients who received the combination of Opdivo 1 mg/kg plus Yervoy 3 mg/kg experienced a higher objective response rate compared to those who received Opdivo 3 mg/kg plus Yervoy 1 mg/kg or Opdivo alone. Patients in the study were heavily pretreated, with most receiving at least two prior treatment regimens. At a minimum follow-up of 7.9 months for the expanded cohort of patients receiving O1:Y3, the ORR was 38%. For patients receiving O3:Y1, at a minimum follow-up of 38.8 months the ORR was 27%, and for patients receiving Opdivo alone, at a minimum follow-up of 37.7 months the ORR was 26%. Median progression-free survival and overall survival, secondary endpoints in the study, were numerically longer in the O1:Y3 treatment cohort compared to the O3:Y1 and Opdivo monotherapy cohorts. The overall safety profile was consistent with prior studies of Opdivo in combination with Yervoy with these dosing schedules. Grade 3 or 4 treatment-related adverse events occurred in 27%, 31% and 39% of patients treated with Opdivo monotherapy, O3:Y1 and O1:Y3, respectively; grade 5 TRAEs were observed in one patient each in the Opdivo monotherapy and O3:Y1 groups; no grade 5 TRAEs were observed in the O1:Y3 group. The combination of Opdivo plus Yervoy was also well tolerated, with 13% discontinuation rate due to TRAEs in the O1:Y3 group and 13% discontinuation rate in the O3:Y1 group. The discontinuation rate due to TRAEs in the Opdivo monotherapy group was 4%.

Tesaro summarized updated Phase 1 GARNET data of TSR-042 in patients with recurrent or advanced microsatellite instability high endometrial cancer during the European Society for Medical Oncology Congress. Blinded, pooled interim safety data from the Phase 3 PRIMA trial of niraparib in patients with first-line ovarian cancer regardless of biomarker status were also presented in a poster discussion session and additional data from the QUADRA trial of niraparib for treatment of late-line ovarian cancer beyond BRCAmut were presented in a poster display. GARNET is a multicenter, open-label, Phase 1 dose-escalation study designed to assess the safety, pharmacokinetics, pharmacodynamics, and clinical activity of TSR-042 in patients with advanced solid tumors. The weight-based dose escalation and fixed-dose safety portions of the GARNET study have been completed. The ongoing cohort expansion portion of GARNET is evaluating TSR-042 at a dose of 500 milligrams every 3 weeks for the first 4 cycles, and 1000 milligrams every 6 weeks thereafter in four cohorts: MSI-H endometrial cancer, MSI-H non-endometrial cancer, MSS endometrial cancer and non-small cell lung cancer. Data presented at ESMO included safety and efficacy data from the cohort of patients with MSI-H endometrial cancer. At the time of data cutoff, 35 patients with MSI-H endometrial cancer had received treatment with TSR-042. Median duration of response was not reached. Preliminary safety findings among the 35 MSI-H endometrial patients indicate TSR-042 is generally well-tolerated. The data support the unique and convenient dose of TSR-042 of 500 mg Q3W for the first 4 doses, then 1000 mg Q6W thereafter. At this dose, TSR-042 maintained serum concentrations required to retain maximum receptor occupancy throughout the dosing cycle. The GARNET study is intended to support a Biologics License Application submission to the U.S. Food and Drug Administration in 2019. PRIMA is a double-blind, randomized Phase 3 study designed to evaluate niraparib versus placebo as maintenance therapy in first-line ovarian cancer patients. The trial remains blinded for efficacy and safety. The findings presented were from evaluable patients with greater than or equal to 30 days of safety data from blinded pooled niraparib and placebo and indicate improved tolerability with niraparib at the individualized starting dose. TEAEs grade greater than or equal to 3 were lower in the individualized dosing group as compared with the group that received a fixed starting dose of 300 mg of niraparib or placebo. There were fewer dose reductions and dose discontinuations in patients treated with the individualized starting dose compared with the fixed starting dose. TEAEs leading to treatment discontinuation remained low for both groups at 7.9% for the fixed starting dose and 5.3% for the individualized starting dose group. QUADRA, a single arm study, was conducted to assess the activity of ZEJULA monotherapy in the fourth-line or later treatment of patients with ovarian cancer, regardless of platinum sensitivity or biomarker status. Niraparib treatment demonstrated durable clinical activity in late-line patients with BRCAmut tumors, with an ORR of approximately 30%, including patients with platinum-sensitive, -resistant, and -refractory disease, and a median duration of response of 9.2 months. The clinical benefit rate at 16 weeks and 24 weeks were 56% and 38%, respectively. A gradient of clinical activity based on platinum sensitivity was demonstrated in the BRCAmut patient population, with greatest activity demonstrated in patients with platinum-sensitive disease, mOS was not reached. However, even patients with platinum-resistant and platinum-refractory disease experienced benefit from niraparib treatment with ORR of 33% and 19%, and mOS of 26.0 and 23.3 months, respectively. Clinical benefit of niraparib extended beyond patients with BRCA mutations in this late-line setting. Patients with non-BRCAmut/HRDpos platinum-sensitive disease had an ORR of 20%. In total, the biomarker-driven population included 98 patients with ORR of 26%, mDOR of 8.3 months, and a mOS of 23.3 months. The safety profile in the QUADRA treatment study was consistent with the safety profile observed in the NOVA maintenance population.