Relapsing classical Hodgkin lymphoma

Bristol Myers Squibb (BMS) has shared positive overall survival (OS) results from a late-stage study of its Opdivo (nivolumab) combination in non-small cell lung cancer (NSCLC). The phase 3 CheckMate-816 study has been evaluating the drug alongside platinum-doublet chemotherapy as a neoadjuvant treatment for adults with resectable cases of the disease. The final analysis of the trial demonstrated a statistically significant and clinically meaningful improvement in the key secondary endpoint of OS for Opdivo-treated patients compared to those receiving neoadjuvant chemotherapy alone. The safety profile of the Opdivo combination was also found to be consistent with previously reported studies, with no new safety signals observed. The results come after CheckMate-816 showed statistical significance in the primary endpoints of event-free survival and pathological complete response, which supported the US approval of Opdivo in this indication in March 2022. “This is the first and only phase 3 study of a neoadjuvant-only immuno-oncology therapy to show a statistically significant [OS] benefit in patients with resectable NSCLC,” said Dana Walker, vice president, global programme lead, late development, oncology, BMS. “The final analysis of OS in the CheckMate-816 study underscores the potential of Opdivo in combination with chemotherapy to provide a meaningful survival benefit for patients with resectable NSCLC,” Walker said. More than 200,000 people are diagnosed with lung cancer in the US every year, with NSCLC accounting for up to 85% of cases. Opdivo is a programmed death-1 immune checkpoint inhibitor designed to use the body’s own immune system to help restore anti-tumour immune response. Beyonds its NSCLC indications, the drug holds approvals to treat certain cases of melanoma, pleural mesothelioma, renal cell carcinoma, classical Hodgkin lymphoma, squamous cell carcinoma of the head and neck, and colorectal cancer, among other cancer types. The latest results come less than two months after an injectable form of Opdivo was approved by the US Food and Drug Administration for most previously approved adult, solid tumour intravenous (IV) Opdivo indications. It is hoped that the subcutaneous formulation will be more convenient for patients, reducing the steps required for preparation and offering an average administration time of three to five minutes compared to 30 minutes for the drug’s IV form.

iStock, JHVEPhoto Leaked data showed that Pfizer’s mevrometostat has strong therapeutic potential in metastatic castration-resistant prostate cancer, while recent readouts also position the pharma as a strong contender in colorectal cancer and bladder cancer. Pfizer on Wednesday nabbed another approval for its antibody-drug conjugate Adcetris, which the FDA cleared for the treatment of certain non-Hodgkin lymphomas. The label expansion covers the use of Adcetris with lenalidomide and rituximab after at least two lines of systemic therapy in certain patients with relapsed or refractory large B-cell lymphoma. These indications include diffuse large B-cell lymphoma (DLBCL) not otherwise specified, DLBCL arising from indolent lymphoma and high-grade B-cell lymphoma. To qualify for Acetris, patients should not be eligible for autologous hematopoietic stem cell transplantation or CAR T therapy, as per Wednesday’s release. “More than 3,500 patients in the U.S. with this aggressive form of non-Hodgkin lymphoma experience treatment failure or relapse after two prior lines of therapy” each year, Pfizer’s chief oncology officer Roger Dansey said in a statement. Adcetris’ expansion into this indication underlines its role “as an existing standard of care with overall survival improvement shown for certain types of lymphomas,” Dansey continued, adding that the antibody-drug conjugate can now provide patients and physicians with an alternative to CAR T therapies and chemotherapy for LBCL treatment. Pfizer established the efficacy and safety of Adcetris in DLBCL via the Phase III ECHELON-3 study, which found that Adcetris plus lenalidomide and ritxumab lowered the risk of death by 37% versus placebo in patients with relapsed or refractory disease. The drug also led to improvements in overall response rate and progression-free survival. Wednesday’s label expansion brings Adcetris’ total number of indications up to eight. The antibody-drug conjugate is also approved for various types of anaplastic large cell lymphoma, peripheral T-cell lymphoma and classical Hodgkin lymphoma. Pfizer has been on a winning streak in cancer recently. Earlier this week, leaked Phase I data set to be presented at the ASCO Genitourinary Cancers Symposium showed that its investigational EZH2 blocker mevrometostat, when used with standard hormone therapy, could reduce disease progression rates by half in patients with metastatic castration-resistant prostate cancer. Last week, the pharma announced that Braftovi significantly boosted survival in the Phase III BREAKWATER study in colorectal cancer, opening up a path for the kinase inhibitor’s full approval. Last month, Pfizer also revealed that its PD-1 candidate sasanlimab—when combined with Bacillus Calmette-Guérin (BCG) immunotherapy—could elicit “ clinically meaningful and statistically significant ” improvement in event-free survival among patients with non-muscle invasive bladder cancer, as compared with BCG alone.

After multiple clinical failures, it’s finally the end of the road for Merck’s TIGIT program. The company is dropping development of its anti-TIGIT candidate vibostolimab after two more Phase 3 studies of a fixed-dose combination with Keytruda ended in disappointment. Merck is also discontinuing a separate LAG-3 targeting antibody asset called favezelimab, which it was also testing alongside Keytruda, according to a company release Tuesday. The pipeline cuts mean Merck won’t be able to stave off generic competition for its blockbuster PD-1 medicine by launching fixed-dose combinations with other targeted therapies, Leerink analysts wrote Tuesday. They added that the drugmaker will instead have to focus on converting patients to a subcutaneous formulation of Keytruda, which could launch as soon as next year. The decision to nix vibostolimab was made after two trials of the drug plus Keytruda in certain patients with non-small cell lung cancer — KeyVibe-003 and KeyVibe-007 — met prespecified futility criteria for the overall survival primary endpoint. These flops add to a spate of late-stage disappointments earlier this year in small cell lung cancer and skin cancer . The company is also axing the KeyVibe-006 test of vibostolimab plus Keytruda and chemoradiotherapy in stage 3 NSCLC, which is still enrolling, according to clinicaltrials.gov. Merck did not offer much explanation of what drove the most recent failures, but the Leerink analysts said TIGIT/PD-1 combinations tend to have high levels of toxicity that can lead to patients discontinuing treatment, making it difficult to establish a long-term survival benefit. Merck is not the only drugmaker that has struggled with developing TIGITs. Last month, Roche’s candidate tiragolumab plus its PD-L1 drug Tecentriq missed the OS primary endpoint in a registrational NSCLC test. But there’s still potential for TIGIT drugs that are Fc-incompetent because they could have better safety, the Leerink analysts said. These include Gilead and Arcus’ domvanalimab and Compugen’s COM902. Elsewhere, Merck stopped enrollment in the Phase 3 KEYFORM-008 trial of a fixed-dose combination of favezelimab and Keytruda in certain patients with relapsed or refractory classical Hodgkin lymphoma as it ended the broader KEYFORM development program. The company said the decision was not driven by safety concerns. In September, the favezelimab regimen failed a separate study in metastatic colorectal cancer.