Spencer Feldman

For patients with unresectable stage 3 EGFR-mutant non-small cell lung cancer, Tagrisso associated with positive outcomes.

Tagrisso (osimertinib) has been found to be associated with positive outcomes, including improvements in overall survival, among patients with unresectable stage 3 EGFR-mutant non-small cell lung cancer (NSCLC).

These findings, it has been posited, position Tagrisso as the new 

 for this patient population, according to findings from the international phase 3 LAURA study presented at the European Lung Cancer Congress (ELCC) 2025.

“In summary, this updated overall survival analysis from the LAURA study demonstrates an improved favorable trend for overall survival benefit with [Tagrisso] over placebo,” stated Dr. Suresh S. Ramalingam in his presentation of the data at the ELCC meeting. “This was seen despite the high proportion of patients in the placebo group that went on to receive another third generation [tyrosine kinase inhibitor], specifically [Tagrisso], nearly 80%.”

“And we also showed that there are clinically meaningful improvements for [Tagrisso] over placebo in time to first subsequent therapy, progression-free survival 2 and time to second subsequent therapy. … In conclusion, these data further substantiate the fact that [Tagrisso] after definitive chemo radiotherapy is the new standard of care for patients with locally advanced non-small cell lung cancer bearing an EGFR exon 19 or 21 mutation.”

Ramalingam is the executive director of the Winship Cancer Institute of Emory University as well as an associate vice president for cancer of Woodruff Health Sciences Center, both in Atlanta.

Results from the LAURA trial supported the U.S. Food and Drug Administration’s September 2024 

 for adults with locally advanced, unresectable stage 3 NSCLC whose disease has not progressed during or after concurrent or sequential platinum-based chemoradiation therapy and whose tumors have EGFR exon 19 deletions or exon 21 L858R mutations. The trial was held at more than 145 centers in more than 15 counties including the United States as well as in Europe, South America and Asia, according to a news release issued by AstraZeneca, the manufacturer of Tagrisso.

Updated results from the trial presented at the recent ELCC meeting showed an improvement in overall survival among patients treated with Tagrisso versus placebo, with median overall survival times of 58.8 months and 54 months, respectively. Notably, 78% of patients on placebo received subsequent treatment with Tagrisso after experiencing disease progression, according to the news release.

In the trial, patients underwent chemoradiotherapy and then, if their disease had not progressed within six weeks, they were randomized to treatment with Tagrisso (143 patients) or to receive placebo (73 patients).

With a Nov. 29, 2024 data cut-off date, the updated overall survival analysis was based on 66 events, with a median overall survival follow-up of 39.4 months in the Tagrisso arm and 35.2 months in the placebo arm.

Of the 143 patients in the Tagrisso group, 48% remained on study treatment, 38% began a first subsequent therapy and 14% received no subsequent treatment. For patients in the placebo group, those respective rates were 5%, 82% and 12%.

The median time to first subsequent treatment was 43.8 months in the Tagrisso arm and 9.5 months in the placebo arm, while median progression-free survival 2 times were 48.2 months and 47.4 months, respectively. Additionally, the median time to second subsequent therapy was not reached in the Tagrisso arm and 47.4 months in the placebo arm.

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Tagrisso (osimertinib) has demonstrated significant improvements in overall survival for patients with unresectable stage 3 EGFR-mutant NSCLC, establishing it as the new standard of care. The international phase 3 LAURA study, presented at the ELCC 2025, showed that Tagrisso outperformed placebo in overall survival, time to first subsequent therapy, and progression-free survival 2. Despite a high crossover rate to Tagrisso in the placebo group, the results were compelling. The FDA approved Tagrisso in September 2024 for this patient population, reinforcing its clinical significance.

Tagrisso is associated with positive outcomes among patients with unresectable stage 3 EGFR-mutant non-small cell lung cancer. 

Tagrisso May Improve Survival in Advanced EGFR-Mutant NSCLC

For patients with EGFR-mutant non-small cell lung cancer, the COCOON trial regimen reduced dermatologic side effects, phase 2 trial data showed.

Among patients with EGFR-mutant non-small cell lung cancer, the COCOON trial regimen (Rybrevant [amivantamab] plus Lazcluze [lazertinib] plus enhanced dermatologic management) significantly reduced the incidence of grade 2 (moderate) or higher dermatologic side effects, according to phase 2 COCOON study findings presented at the 

"At the first pre-planned interim analysis, the primary end point of COCOON was met,” said Dr. Nicolas Girard during the presentation of these findings. “We see that the prophylactic COCOON dermatologic management regimen significantly reduced the incidence of grade two or higher dermatologic [side effects]. This is a two-fold reduction of these [side effects], a two-fold reduction in grade three dermatologic [side effects and] a two-fold reduction in discontinuation due to [side effects], which allows more patients to remain on treatment."

The trial found that the COCOON trial, also referred to as COCOON DM, reduced grade 2 or higher dermatologic side effects by 50% compared with the standard of care (Rybrevant plus Lazcluze plus standard dermatologic management). A two-fold reduction in grade 2 or higher dermatologic side effects were observed when compared with standard of care (38.6% versus 76.5%, respectively) in the first 12 weeks.

Additionally, there was a two-fold reduction in grade 3 (severe) dermatologic side effects with COCOON DM compared with standard of care (4.3% versus 8.8%). The study also reported a three-fold reduction in the number of participants who reported two or more different grade 2 or higher dermatologic side effects with COCOON DM versus standard of care (6% versus 18%).

For dermatologic side effects, 16% (11 patients) of patients receiving COCOON DM experienced dose interruption compared with 34% (23 patients) in the standard of care group. Dose reduction occurred in 7% (5 patients) of the COCOON DM group and 19% (13 patients) of the standard of care group. Discontinuation due to dermatologic side effects was 1% (1 patient) in the COCOON DM group and 4% (3 patients) in the standard of care group.

When considering any side effects, dose interruption was reported in 50% (35 patients) of the COCOON DM group and 54% (37 patients) of the standard of care group. Dose reduction for any side effects was 21% (15 patients) in the COCOON DM group and 31% (21 patients) in the standard of care group. Discontinuation due to any side effects occurred in 11% (8 patients) of the COCOON DM group and 19% (13 patients) of the standard of care group.

Venous thromboembolism was observed in 6% of participants with COCOON DM and 7% with standard of care.

The COCOON DM regimen included an oral doxycycline or minocycline for 12 weeks followed by topical clindamycin lotion on the scalp. Additionally, chlorhexidine was administered to the nails and ceramide-based moisturizer was applied to the body and face.

The standard of care regimen included general skin prophylaxis per local practice and reactive treatment, such as topical corticosteroids and systemic antibiotics.

At a median follow-up of 4.2 months, 138 participants received at least one dose of Rybrevant plus Lazcluze (safety analysis set) and had at least 12 weeks of follow-up. The median duration of Rybrevant plus Lazcluze treatment was 4.2 months with COCOON DM, compared to 4.1 months with standard of care.

The median age of participants in both the COCOON DM (70 patients) and SoC DM (68 patients) groups was 62.5 years. In the COCOON DM group, 42 participants were female (60%), compared to 37 (54%) in the standard of care group.

In the COCOON DM group, 35 participants (50%) had EGFR mutations of Ex19del versus 37 patients (54%) in the standard of care group. L858R mutations was reported in 35 participants (50%) in the COCOON DM group and 31 (46%) in the standard of care group.

The primary end point was the incidence of grade 2 or higher dermatologic side effects in the first 12 weeks after initiation of Rybrevant plus Lazcluze treatment.

First-line Rybrevant plus Lazcluze is Food and Drug Administration, and European Medicines Agency approved for EGFR-mutant advanced non-small cell lung cancer based on results from the phase 3 MARIPOSA study.

The COCOON trial is now fully enrolled with 201 patients and additional results are planned to be presented at upcoming congresses.

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The COCOON trial regimen, combining Rybrevant, Lazcluze, and enhanced dermatologic management, significantly reduced grade 2 or higher dermatologic side effects in EGFR-mutant non-small cell lung cancer patients. The trial demonstrated a two-fold reduction in both moderate and severe dermatologic side effects compared to standard care. Additionally, the regimen decreased dose interruptions, reductions, and discontinuations due to side effects. The COCOON DM regimen included specific prophylactic measures, contrasting with the standard care's general skin prophylaxis. The trial is fully enrolled, with further results anticipated at future congresses.

The COCOON trial regimen reduced dermatologic side effects in patients with EGFR-mutant non-small cell lung cancer, phase 2 trial data showed.

COCOON Trial Regimen Reduces Dermatologic Side Effects in Mutated Lung Cancer

A phase 1 clinical trial evaluating APR-1051 has dosed a patient with HPV-positive head and neck squamous cell carcinoma.

A patient with human papillomavirus (HPV)-positive head and neck squamous cell carcinoma (HNSCC) has been dosed in ACESOT-1051, a phase 1 clinical trial evaluating APR-1051 in advanced solid tumors with cancer-associated gene alterations.

The development was announced in a news release from clinical-stage biopharmaceutical company Aprea Therapeutics, Inc.

APR-1051, according to the National Cancer Institute, is an oral inhibitor of the WEE1 protein kinase. Overexpression of WEE1 occurs in several different cancer types, with a high expression of WEE1 associated with poor outcomes. APR-1051 treatment is intended, by inhibiting WEE1, to promote premature cell division and prolonged blocking of the cell cycle, resulting in an accumulation of unrepaired DNA damage and leading to the death of susceptible tumor cells.

The patient with HPV-positive HNSCC was the first patient to be dosed in Cohort 5 of ACESOT-1051, receiving 70 milligrams once daily of APR-1051, according to the news release. Open-label data from the study are expected to be released in the second half of 2025, Aprea reported.

Oropharynx: the middle part of the throat, behind the mouth, including the soft palate, the side and back walls of the throat, the tonsils and the back third of the tongue.

Pharmacokinetics: study of how the drug is absorbed, distributed, metabolized and excreted in the body, providing insight into the drug's action and optimal dosing.

Pharmacodynamics: assessment of the drug's biochemical and physiological effects on the body and its mechanism of action against cancer cells.

HPV-positive cancers, according to the news release, are among those potentially susceptible to WEE1 inhibition, and approximately 70% of the 20,000 cases oropharyngeal squamous cell carcinoma, or HNSCC that occurs in the oropharynx, diagnosed each year in the United States are attributable to HPV.

The ACESOT-1051 trial, evaluating APR-1051 monotherapy among patients with advanced solid tumors, is currently recruiting, with an anticipated eventual enrollment of 79 patients, according to its listing on clinicaltrials.gov. The trial is being held at three locations in Texas, including The University of Texas MD Anderson Cancer Center in Houston, NEXT Oncology – Dallas in Irving and NEXT Oncology – San Antonio. The trial has an estimated primary completion date of June 2027, and an estimated study completion date of June 2028, according to the listing.

“Enrollment of the first patient with HPV+ head and neck cancer in the phase 1 ACESOT-1051 trial is an important step and is in line with our goal of identifying patient populations most likely to benefit from WEE1 inhibition,” said Dr. Philippe Pultar, senior medical advisor and lead WEE1 clinical development of Aprea. “We are pleased with the progress of the trial and encouraged by the safety profile of APR-1051 to date. We look forward to continuing the study as we work toward identifying the optimal dose for future studies. We continue to believe that APR-1051 has best in class potential.”

Cancers known as head and neck cancers, according to the National Cancer Institute, usually begin the squamous cells lining the mucosal surfaces of the head and neck, such as inside the mouth, the throat and the voice box, and are referred to as squamous cell carcinomas of the head and neck.

ACESOT-1051 has been designed to evaluate the safety, pharmacokinetics, pharmacodynamics and preliminary effectiveness of APR-1051. The drug will be administered once a day for 28-day cycles. Part 1 of the study will be a dose-escalation phase, expected to enroll up to 39 patients, with Part 2 with up to 40 patients being designed for dose optimization with the goal of selecting a recommended phase 2 dose, according to the news release, which stated that the study will eventually be performed at up to 10 sites across the United States.

For more information on the trial, use the trial ID, NCT06260514, at clinicaltrials.com.

A patient with HPV-positive head and neck squamous cell carcinoma has been dosed in a phase 1 trial evaluating APR-1051, an oral WEE1 protein kinase inhibitor. This trial, ACESOT-1051, aims to assess the safety, pharmacokinetics, pharmacodynamics, and preliminary effectiveness of APR-1051 in advanced solid tumors. The trial is recruiting at three Texas locations, with an anticipated enrollment of 79 patients. The study's primary completion is expected by June 2027, with full completion by June 2028. Open-label data is anticipated in the second half of 2025.

A patient with HPV-positive head and neck squamous cell carcinoma was dosed in a phase 1 clinical trial evaluating APR-1051.

Patient With Head and Neck Cancer Dosed in Trial of APR-1051

Relacorilant plus chemotherapy met its primary end goal of progression-free survival and overall survival. 

The primary end goal was met in a phase 3 trial of relacorilant plus nab-paclitaxel chemotherapy in patients with platinum resistant ovarian cancer, which improved progression-free survival, according to the drug’s manufacturer, Corcept Therapeutics Inc.

Recent findings that supported this decision come from the phase 3 trial ROSELLA.

“Patients with advanced ovarian cancer have few good treatment options and, unfortunately, patients with recurrent disease eventually develop resistance to available therapies,” Dr. Alexander B. Olawaiye said in the news release. “The ROSELLA results represent an important advancement in the development of a treatment for patients with platinum-resistant ovarian cancer.”

Olawaiye is the Director of gynecological cancer research at Magee-Women’s Hospital of the University of Pittsburgh and Principal Investigator in the ROSELLA trial.

In the ROSELLA trial, patients treated with relacorilant plus nab-paclitaxel had a 30% lower risk of disease progression than those receiving nab-paclitaxel alone. Median progression-free survival by blinded independent central review was 6.5 months versus 5.5 months, respectively. An interim overall survival analysis showed a significant improvement with relacorilant, with a median of 16 months compared with 11.5 months for nab-paclitaxel alone.

Overall survival: the time from treatment initiation until death from any cause.

Progression-free survival: the time at which half of the patients in a clinical trial experience disease progression or death.

Orphan drug designation: a status granted by regulatory agencies to drugs developed for rare diseases, providing benefits like market exclusivity and tax credits.

Regarding safety, relacorilant was well tolerated, with no new safety signals. Safety and tolerability were consistent between groups, as seen in the company’s phase 2 trial.

Full results will be presented at a medical conference this year. Findings from Corcept’s phase 2 trial in platinum-resistant ovarian cancer were published in the 

“Platinum-resistant ovarian cancer poses a significant treatment challenge. The ROSELLA results demonstrate that relacorilant in combination with nab-paclitaxel has the potential to become a key strategy to help improve patient outcomes,” Dr. Domenica Lorusso, Director of the Gynaecological Oncology Unit at Humanitas Hospital San Pio X, Milan, and Full Professor of Obstetrics and Gynaecology, Humanitas University, Rozzano and investigator in the ROSELLA trial, said in the news release.

The ROSELLA trial enrolled 381 patients with platinum-resistant ovarian cancer at sites in the United States, Europe, South Korea, Brazil, Argentina, Canada and Australia. Biomarker selection was not required. Patients were randomly assigned to receive either relacorilant plus nab-paclitaxel or nab-paclitaxel alone.

The trial has dual primary end goals: progression-free survival by blinded independent central review and overall survival. A positive outcome is achieved if either end goal is met.

Relacorilant is an oral therapy and a selective glucocorticoid receptor antagonist that modulates cortisol activity by binding to the glucocorticoid receptor without affecting other hormone receptors, as per the release. Corcept is studying relacorilant for ovarian cancer and other serious conditions, including endogenous hypercortisolism, also known as Cushing’s syndrome, and prostate cancer.

Relacorilant has been designated an orphan drug by the Food and Drug Administration and the European Commission for the treatment of hypercortisolism and by the European Commission for ovarian cancer.

“The improvement in survival seen in ROSELLA, without an increased safety burden, brings us closer to delivering a new standard-of-care treatment for patients with platinum-resistant ovarian cancer,” Bill Guyer, Corcept’s Chief Development Officer, said in the news release. “We deeply appreciate the patients and investigators who participated in the trial, and we look forward to presenting the trial’s full results in the coming months. We expect to submit our [new drug application] in the third quarter and our [Marketing Authorization Application] shortly thereafter.”

A phase 3 trial, ROSELLA, demonstrated that relacorilant combined with nab-paclitaxel significantly improved progression-free survival in patients with platinum-resistant ovarian cancer. The trial showed a 30% reduction in disease progression risk and a median progression-free survival of 6.5 months compared to 5.5 months with nab-paclitaxel alone. Relacorilant was well tolerated, with no new safety concerns. The trial enrolled 381 patients globally, and the results suggest relacorilant could become a key treatment strategy. Full results will be presented at an upcoming medical conference.

The phase 3 trial showed relacorilant with chemotherapy improved progression-free and overall survival in platinum-resistant ovarian cancer.

Spencer Feldman

Tagrisso May Improve Survival in Advanced EGFR-Mutant NSCLC

COCOON Trial Regimen Reduces Dermatologic Side Effects in Mutated Lung Cancer

Patient With Head and Neck Cancer Dosed in Trial of APR-1051

Relacorilant Plus Chemo Meets Primary Goal in Ovarian Cancer Trial

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