Posts Tagged ‘Opdivo (nivolumab)’

Immuno-Therapy Strategies on BioMarker’s cutoff value for defining PD-L1 positive/negative patients: First-line and Second-line setting – FDA stand on BMS’s “Test-free Prescribing” in Opdivo (nivolumab) vs Merck’s “Companion Diagnostic” in Keytruda (pembrolizumab) vs Genetech’s “Complementary Diagnostics” and “Companion Diagnostic”?? in Tecentriq (atezolizumab)

Reporter: Aviva Lev-Ari, PhD, RN


UPDATED on 3/11/2019

Roche’s I-O drug Tecentriq picks up key first-in-class breast cancer nod

In a first for the immuno-oncology field, Roche’s Tecentriq has a big new approval in breast cancer. And once again, the Swiss drugmaker has nabbed a piece of the immuno-oncology market all for itself.

On Monday, the FDA greenlighted the immuno-oncology drug, in combination with Celgene chemo drug Abraxane, as a treatment for patients with triple-negative breast cancer (TNBC) whose tumors express the protein PD-L1. The go-ahead makes it the first immunotherapy regimen cleared in TNBC—and in breast cancer in general.

Regulators based their positive decision on data presented last fall that showed that adding Tecentriq to Abraxane in newly diagnosed patients could pare down the risk of disease worsening or death by 20%. The duo staved off progression by a median 7.2 months, compared with 5.5 months for Abraxane on its own.

Now, Roche will lead the way in TNBC without market competition from its PD-1/PD-L1 nemeses—at least for now. Tecentriq’s other two therapy areas, bladder cancer and lung cancer, are ultracrowded, thanks to drugs such as Merck’s Keytruda and Bristol-Myers Squibb’s Opdivo, both of which hit the scene before Tecentriq did.

“The response from the physician community has been phenomenal,” Amreen Husain, M.D., global development team leader for Roche immuno-oncology, said in an October interview.

RELATED: ESMO: Roche’s Tecentriq posts ‘unprecedented’ benefit in triple-negative breast cancer

But when it comes to breast cancer, Roche is used to leading the way, and the company will no doubt lean on its marketing expertise—gleaned through years selling drugs like Herceptin and, more recently, Perjeta and Kadcyla—to get Tecentriq off the ground.

RELATED: Can Kadcyla give Roche a softer landing when Herceptin biosims hit? New data could help

Meanwhile, the approval is an exciting one for doctors and patients who’ve battled the notoriously tough-to-treat disease for years with few good options.



UPDATED on 2/14/2019

Dive Insight:

Checkpoint inhibitors like Merck’s Keytruda (pembrolizumab) have changed cancer care across a number of tumor types, but none are currently approved for prostate cancer. Neither are any of three PARP inhibitors currently on the U.S. market for ovarian and breast cancers.

Merck hopes to change that through these late-stage studies, pairing Keytruda with the PARP inhibitor Lynparza (olaparib), chemotherapy and approved prostate cancer agent Xtandi (enzalutamide).

Patients with mCRPC pose a particular challenge to treat. Metastatic cancer has spread to other parts of the body, while castration-resistant tumors have continued to grow despite surgery or treatment to lower the amount of male sex hormones, or androgens, that typically drive prostate cancer.

Current treatment options for this type of prostate cancer are led by Zytiga (abiraterone acetate), a Johnson & Johnson drug now facing generic competition, and Pfizer and Astellas’ Xtandi.

Merck’s Phase 1b/2 study tested four Keytruda combinations, pairing the immunotherapy with both of those current treatment options as well as with chemotherapy and with Lynparza, which is jointly owned by AstraZeneca and Merck.

Results presented Thursday came from a small number of patients, but showed some positive responses in previously treated patients.




UPDATED on 5/1/2018

Dive Insight:

While both Keytruda and Opdivo won initial U.S. approval just months apart in 2014, Bristol-Myers’ drug saw much faster sales growth to start. Securing OKs in first-line lung cancer has been Merck’s ticket to catching Bristol-Myers, and Keytruda sales in the first quarter were roughly even with Opdivo’s.

Merck expects the success of its KEYNOTE-189 study will further drive uptake of Keytruda as a first-line treatment for advanced NSCLC. Results, presented last month at the annual meeting of the American Association of Cancer Research, showed a combination of Keytruda and chemotherapy cut the risk of death in half compared to chemotherapy alone.

Importantly, data supported the combination’s benefit across varying levels of PD-L1 expression , a biomarker used to identify patients most likely to respond to immunotherapy. Merck previously won a conditional approval for the combo from a smaller study, but physicians have been hesitant to broadly prescribe without further data.

Now, impressive results in hand, Merck hopes more doctors will prescribe Keytruda plus chemotherapy to NSCLC patients with PD-L1 expression levels below 50% or even below 1% — patient populations currently not served by Keytruda monotherapy.



UPDATED on 3/26/2018

Gaining steam in PD-1/L1 race, Roche reports positive PhIII OS data on Tecentriq combo in NSCLC

by brittany meiling — on March 26, 2018 06:29 AM EDT



UPDATED on 3/20/2018

In a phase 3 study, Roche’s Tecentriq combined with chemo beat out solo chemo at cutting the risk of disease worsening or death in previously untreated patients with the squamous form of the disease. As of now, researchers haven’t seen evidence of a benefit to overall survival, but the trial, dubbed IMpower131, is continuing to collect that data.

The results hand Roche the chance to nab a first-to-market lead in the front-line squamous setting. Squamous NSCLC affects just 25% to 30% of all NSCLC patients, but it’s more complicated, and patients have fewer treatment options than those with non-squamous NSCLC, Jefferies analyst Ian Hilliker wrote in a note to clients. Hilliker predicts $1.1 billion in peak sales for Tecentriq in that set of patients.




UPDATED on 11/21/2017

Roche Cancer Drug Rises To Challenge Merck, Bristol-Myers

Roche’s study had three arms. All patients received carboplatin and paclitaxel, the cancer drug once sold as Taxol. The control group also received Avastin, one of Roche’s best-selling cancer drugs. Then two groups got Tecentriq, one with Avastin and one without. What Roche has announced today is that the Avastin-Tecentriq-chemotherapy combination did better than Avastin and chemotherapy alone, and that the survival results so far are “encouraging.” That leaves a big question: how are the patients who got Tecentriq, but not Avastin, doing?




UPDATED on 7/25/2017

Close to a year after Merck $MRK won an accelerated FDA OK to use its PD-1 checkpoint star Keytruda for treating second-line cases head and neck squamous cell carcinoma in combination with platinum-containing chemo, the pharma giant announced that its big Phase III study for that indication failed.

The pivotal KEYNOTE-040 trial failed to meet the primary endpoint on overall survival in comparing the blockbuster checkpoint against standard therapies, the pharma giant reported. But the current approval stands nevertheless, Merck said in a statement.

“The company noted that the FDA remains comfortable with the drug’s current accelerated approval in this indication despite the trial results,” observed Leerink’s Seamus Fernandez. “Importantly, Keytruda appears to have another shot on goal for full approval in H&N cancer, as the Keynote-048 study in first-line patients could, if positive, serve as the confirmatory trial.”



UPDATED on 5/11/2017

Merck increases grip on its lead in lung cancer, winning approval for Keytruda/chemo combo as first-line therapy

UPDATED on 5/10/2017

Roche’s shocking Tecentriq fail raises red flag for bladder cancer rivals

Roche’s Tecentriq wasn’t supposed to fail its phase 3 trial in second-line bladder cancer. But that’s what it just did—and the data shortfall not only endangers the drug’s conditional FDA approval, but could augur trouble ahead for other checkpoint inhibitors that followed Tecentriq into the field.

Tecentriq, approved last year on the basis of phase 2 data showing a durable response to the drug, failed to prove it could actually prolong patients’ lives, the company said Wednesday. The bladder cancer indication, Tecentriq’s first, accounts for about 70% of the med’s current sales, analysts say, and the FDA could well decide to strike that approval off the drug’s label.

“[W]e assume that this will put this indication at risk of being removed from the label,” Leerink analyst Seamus Fernandez wrote Wednesday morning, noting that the results were unexpected. “This comes as a surprise to us, considering Merck’s Keytruda showed an overall survival benefit.”



UPDATED on 4/13/2017

World’s Top Ten Cancer Drugs by 2020  (million USD)


Opdivo Setback May Yield Lessons for Pharma Advancing Immunotherapies With PD-L1 Testing


UPDATED on 10/9/2016

Opdivo (nivolumab) Shows Durable Response in Longest Follow-up for a PD-1 Inhibitor in Previously Treated Advanced Non-Small Cell Lung Cancer


Opdivo (nivolumab) Shows Durable Response in Longest Follow-up for a PD-1 Inhibitor in Previously Treated Advanced Non-Small Cell Lung Cancer

Updated data from CheckMate -057 and -017 show Opdivo-treated patients had tripled the duration of response compared to those treated with docetaxel, with a minimum follow-up of two years

In CheckMate -057, durable responses and complete responses were observed with Opdivo in both PD-L1 expressors and non-expressors

Patient-reported outcomes from CheckMate -057 show favorable overall health status with Opdivo versus docetaxel in previously treated advanced non-small cell lung cancer patients

Bristol-Myers Squibb Company (NYSE: BMY) announced today updated results from two pivotal Phase 3 studies, CheckMate -057 and CheckMate -017, which showed more than one-third of previously treated metastatic non-small cell lung cancer (NSCLC) patients in both trials experienced ongoing responses with Opdivo, compared to no ongoing responses in the docetaxel arm. The median duration of response (DOR) with Opdivo versus docetaxel in CheckMate -057 was 17.2 months (95% CI: 8.4, NE) and 5.6 months (95% CI: 4.4, 6.9), respectively, and in CheckMate -017 it was 25.2 months (95% CI: 9.8, 30.4) and 8.4 months (95% CI: 8.4, NE), respectively. In CheckMate -057, patients with PD-L1 ≥1% had a median DOR of 17.2 months (95% CI: 8.4, NE) and in patients with PD-L1 <1%, it was 18.3 months (95% CI: 5.5, NE). In both studies, durability of response was observed in both PD-L1 expressors and non-expressors, and in CheckMate -057, one out of the four complete responses occurred in a patient with <1% PD-L1 expression.

There were no new safety signals identified for Opdivo in the pooled safety analysis from both studies. No new treatment-related deaths occurred between one and two years’ minimum follow-up despite the longer treatment exposure, and new events were observed in 11/418 patients with an additional one year of follow up.

These findings were presented today, October 9, during a poster discussion session at the 2016 European Society for Medical Oncology Congress from 3:46-4:06 p.m. CEST (Abstract #1215PD).

“Further evaluation of Opdivo in previously treated non-small cell lung cancer showed continued superior survival and the potential for durable responses compared to docetaxel across histologies in this patient population,” said Martin Reck, M.D., Ph.D., head of thoracic oncology at the Hospital Grosshansdorf. “Notably, the median duration of response with Opdivo was more than three times that observed with docetaxel.”



UPDATED on 9/25/2016

Genentech dives into mRNA, betting $310M on BioNTech’s personalized cancer vaccine tech

For a review of all the complexities involved in the emerging market for BioMarkers in Immuno-Therapy, see

Opdivo Setback May Yield Lessons for Pharma Advancing Immunotherapies With PD-L1 Testing


PD-L1 testing as part of the tumor profiling workup for patients. Diaceutics’ surveys show a sharp uptick in the number of labs offering PD-L1 testing over the past year-and-a-half and 52 labs in the US offer at least one PD-L1 test. The company also reviewed biomarkers being studied in 95 Phase II/III NSCLC, and found that approximately half are incorporating patients’ PD-L1 status either alone or in combination with other markers, such as EGFR and ALK mutations.

At Cancer Genetics over the past year, there has also been a notable ramp up in orders for PD-L1 testing for lung cancer patients, but also for melanoma and head and neck cancer patients.

Labs are also challenged by having to decide whether to invest in validating and offering all four FDA-approved PD-L1 tests. “If you look from a laboratory perspective, in the ideal world, you need one test, and clear instructions about the algorithm and cutoff values to assign patients to treatment,” Braendle said. “Four different tests creates quite a confusing situation for the labs and the physicians.”


Diaceutics Group Report Reveals Significant Real-Time PD-L1 Testing Gaps in the US



Opdivo Setback May Yield Lessons for Pharma Advancing Immunotherapies With PD-L1 Testing



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