October 23, 2023
Rybrevant and Lazertinib Combination Shows Promise in EGFR-NSCLC First-Line Therapy
Janssen presented the Phase 3 MARIPOSA study, demonstrating the efficacy of Rybrevant (amivantamab) plus lazertinib versus osimertinib in patients with EGFR-NSCLC as first-line therapy. The combination reduced the risk of disease progression or death by 30 percent.
After a median follow-up of 22 months, the median progression-free survival was 23.7 months in patients on Rybrevant plus lazertinib, compared to 16.6 months in patients on osimertinib.
In patients with CNS-only first progressions, the median PFS was 27.5 months in patients on Rybrevant (amivantamab) plus lazertinib, as opposed to 18.5 months in patients on osimertinib.
The median duration of response (DOR) was 25.8 months in patients on Rybrevant (amivantamab) plus lazertinib, while it was 16.8 months in patients on osimertinib.
The adverse events observed were consistent with the safety profile of each product, primarily consisting of Grade 1 or 2 adverse events.
October 23, 2023
Datopotamab Deruxtecan Shows Significant Progression-Free Survival Benefit in TROPION-Lung01 Phase III Trial for Previously Treated Non-Small Cell Lung Cancer.
AstraZeneca and Daiichi Sankyo's datopotamab deruxtecan reduce the risk of disease progression or death by 25% in the overall population and by 37% in patients with non-squamous NSCLC tumours. Datopotamab deruxtecan is the first antibody-drug conjugate to demonstrate a statistically significant improvement in PFS over docetaxel in this setting of high unmet need.
Positive outcomes from the pivotal TROPION-Lung01 Phase III trial reveal that datopotamab deruxtecan (Dato-DXd) offers a substantial improvement in progression-free survival (PFS) compared to docetaxel, the current standard of care, for patients with locally advanced or metastatic non-small cell lung cancer (NSCLC). These patients had previously received at least one line of therapy.
Datopotamab deruxtecan, a TROP2-directed DXd antibody-drug conjugate (ADC) engineered specifically, is being jointly developed by AstraZeneca and Daiichi Sankyo.
In the dual primary endpoint analysis, datopotamab deruxtecan reduced the risk of disease progression or death by 25% when compared to docetaxel.
Median PFS was 4.4 months for patients treated with datopotamab deruxtecan, whereas it was 3.7 months for those treated with docetaxel. The results also revealed a confirmed objective response rate (ORR) of 26.4% in patients treated with datopotamab deruxtecan, compared to 12.8% in patients treated with docetaxel.
In the case of patients with non-squamous NSCLC, datopotamab deruxtecan showed a clinically meaningful benefit by reducing the risk of disease progression or death by 37% when compared to docetaxel. The median PFS for datopotamab deruxtecan-treated patients was 5.6 months, while it was 3.7 months for docetaxel-treated patients. An observed confirmed ORR of 31.2% was noted with datopotamab deruxtecan, compared to 12.8% in patients on docetaxel.
Datopotamab deruxtecan exhibited a favourable safety profile when compared to docetaxel, with no new safety concerns identified.
Lilly's Retevmo showed promising results as first-line therapy in patients with RET-positive NSCLC.
In the Phase 3 LIBRETTO-431 study, Retevmo was evaluated for its efficacy in patients with RET fusion-positive non-small cell lung cancer (NSCLC) who had not received prior treatment. Patients with advanced or metastatic disease were included in the trial.
Patients were randomly assigned to receive either Retevmo or a combination of pemetrexed and platinum-based chemotherapy (cisplatin or carboplatin) with or without pembrolizumab, a standard-of-care treatment. This trial is the first to compare the safety and effectiveness of a targeted therapy against a combination of a PD-1 inhibitor and chemotherapy in a specific group of NSCLC patients identified by biomarkers.
Among the patients who received Retevmo in the group with pembrolizumab, the median progression-free survival (PFS) was 24.8 months, whereas the control arm showed a median PFS of 11.2 months. The overall response rate (ORR) for Retevmo patients was 83.7%, compared to 65.1% in the control arm.
Furthermore, intracranial baseline assessments were conducted for 192 patients within the central nervous system (CNS)-pembrolizumab group. The time to CNS progression was notably longer for patients receiving Retevmo than those in the control arm. Specifically, 6.7% of patients on Retevmo experienced a first event of CNS progression, as opposed to 18.1% in the control arm.
October 21, 2023
Rybrevant Plus Chemotherapy Shows Remarkable Efficacy in Treating EGFR Exon 20 Insertion Mutation-Positive NSCLC: PAPILLON Study Highlights
New findings from the Phase 3 PAPILLON study have unveiled the potential of Rybrevant (amivantamab) in conjunction with chemotherapy (carboplatin-pemetrexed) as a promising first-line treatment for patients grappling with advanced non-small cell lung cancer (NSCLC) carrying EGFR exon 20 insertion mutations. The new data showed a 60 percent reduction in disease progression or mortality risk in previously untreated patients with advanced or metastatic NSCLC bearing these specific mutations compared to those receiving chemotherapy alone.
Additionally, Rybrevant plus chemotherapy exhibited substantial enhancements in the objective response rate (ORR) and progression-free survival (PFS) after the first subsequent therapy (PFS2).
At median follow-up of 14.9 months disclosed that patients treated with Rybrevant plus chemotherapy experienced significantly prolonged PFS compared to their counterparts who solely received chemotherapy (median, 11.4 months versus 6.7 months, respectively). Impressively, at the 18-month mark, 31 percent of patients administered with Rybrevant and chemotherapy combo were alive and free from disease progression, compared to a mere 3 percent for those on chemotherapy alone.
The advantages of PFS associated with Rybrevant plus chemotherapy extended consistently across various patient subgroups.
The combination of Rybrevant and chemotherapy achieved an ORR of 73 percent, in contrast to the 47 percent ORR observed in patients solely undergoing chemotherapy. Moreover, the median PFS2 was significantly more prolonged with Rybrevant plus chemotherapy than chemotherapy alone, further underscoring the potential suitability of Rybrevant and chemotherapy as a first-line approach.
Notably, a substantial proportion of patients receiving chemotherapy alone (76 percent) subsequently received Rybrevant as their second-line therapy. In an interim overall survival (OS) analysis, patients treated with Rybrevant plus chemotherapy displayed a favourable trend compared to those receiving chemotherapy alone, with two-year survival rates of 72 percent and 54 percent, respectively.
October 21, 2023
AstraZeneca's new data on Tagrisso aims to treat brain disease in patients with NSCLC.
The results of the FLAURA2 Phase III trial have shed light on the effectiveness of AstraZeneca's Tagrisso (osimertinib) when combined with chemotherapy for EGFR positive non-small cell lung cancer (NSCLC) patients with brain metastases at the trial's outset.
In this specific group of patients, the addition of chemotherapy to Tagrisso led to a notable 42% improvement in central nervous system (CNS) progression-free survival (PFS) compared to Tagrisso used alone. The combined treatment reduced the risk of CNS disease progression or death by 42%. After two years of follow-up, 74% of patients treated with Tagrisso plus chemotherapy had not experienced CNS disease progression or death, contrasting with 54% of patients receiving Tagrisso monotherapy. Furthermore, the data revealed that a greater proportion of patients attained a CNS complete response (CR) when treated with Tagrisso plus chemotherapy (59%), in contrast to those treated with Tagrisso alone (43%).
These findings underscore the potential of combining Tagrisso with chemotherapy as a promising approach to reduce the risk of brain disease progression in patients with EGFR-mutated advanced lung cancer and baseline brain metastases.
October 20, 2023
Merck Presented Positive Results of Keytruda as Neoadjuvant Therapy for NSCLC.
Merck has presented findings from the Phase 3 KEYNOTE-671 trial, which explored the use of Keytruda (pembrolizumab) as a perioperative treatment regimen for resectable stage II, IIIA, or IIIB non-small cell lung cancer (NSCLC) patients. This innovative regimen involved treatment both before surgery (neoadjuvant) and after surgery (adjuvant).
Following the second interim analysis of the trial with a median follow-up of 36.6 months, the neoadjuvant Keytruda plus chemotherapy, followed by Keytruda as a single agent after surgical resection, demonstrated a remarkable 28% reduction in the risk of death compared to neoadjuvant placebo plus chemotherapy followed by adjuvant placebo, regardless of PD-L1 expression. For patients receiving the KEYTRUDA-based regimen, median overall survival (OS) was not reached, while 52.4 months for those in the chemotherapy-placebo regimen. The 36-month OS rates were 71.3% for the Keytruda-based regimen and 64.0% for the chemotherapy-placebo regimen.
As previously disclosed, KEYNOTE-671 had already met the dual primary endpoint of event-free survival (EFS) at the first interim analysis. In this second interim analysis, the EFS benefit persisted, with the Keytruda arm demonstrating an improvement of nearly two and a half years in median EFS compared to the placebo and chemotherapy arm (47.2 months versus 18.3 months, respectively). The 36-month EFS rates were 54.3% for the Keytruda-based regimen and 35.4% for the chemotherapy-placebo regimen.
In response to the OS and EFS results from KEYNOTE-671, the U.S. Food and Drug Administration (FDA) had previously approved KEYTRUDA for the treatment of patients with resectable (tumours≥4 cm or node-positive) NSCLC. The treatment involves the combination of Keytruda with platinum-containing chemotherapy as neoadjuvant treatment, followed by Keytruda as a single agent for adjuvant treatment after surgery.
October 18, 2023
Roche presented effective data in ALK-positive early-stage non-small cell lung cancer.
Roche has unveiled groundbreaking results from the Phase III ALINA study, demonstrating the remarkable effectiveness of Alecensa (alectinib) in reducing the risk of disease recurrence or death by an unprecedented 76% in individuals with ALK-positive early-stage non-small cell lung cancer (NSCLC).
Approximately one in two individuals with early-stage NSCLC face the challenge of disease recurrence following surgery, even with the addition of adjuvant chemotherapy. As a result, there is an urgent need for more effective treatment options to provide the best chance of a cure.
During the initial examination of the Phase III ALINA trial, Roche presented findings that demonstrate a significant and clinically meaningful improvement in the primary endpoint, DFS. These results confirm that Alecensa substantially decreases the risk of disease recurrence or death by 76% compared to platinum-based chemotherapy. This positive outcome is particularly promising for individuals with completely resected stage IB to IIIA ALK-positive NSCLC.
The primary analysis of the ALINA study demonstrated that the median DFS had not yet been reached for patients treated with Alecensa, in contrast to 41.3 months for those receiving chemotherapy, underscoring the remarkable efficacy of Alecensa.
Grade 3 or 4 side effects were reported in 30% of individuals receiving Alecensa, compared to 31% in the chemotherapy group. Importantly, no Grade 5 events were observed in either treatment arm.
October 10, 2023
Merck Unveils Positive Results from KEYNOTE-671 Trial in the Treatment of Resectable NSCLC
Merck shared promising news regarding its Phase 3 KEYNOTE-671 trial. This clinical trial evaluated the effectiveness of Keytruda (pembrolizumab), Merck's anti-PD-1 therapy, as a perioperative treatment for stage II, IIIA, or IIIB non-small cell lung cancer (NSCLC) patients. The trial successfully met its dual primary endpoint: overall survival (OS).
At the pre-specified interim analysis, the combination of Keytruda and chemotherapy before surgery (neoadjuvant), followed by surgical resection and Keytruda as a standalone treatment after surgery (adjuvant), exhibited a significant and clinically meaningful increase in overall survival compared to the group receiving neoadjuvant placebo and chemotherapy, followed by adjuvant placebo.
Crucially, the safety profile of Keytruda in this trial aligned with previous studies, with no identification of new safety concerns. The full results from the analysis of KEYNOTE-671 will be presented at the ESMO Congress 2023 and shared with regulatory authorities worldwide.
Moreover, the KEYNOTE-671 trial had previously achieved the other primary endpoint of event-free survival (EFS) during its first interim analysis, along with critical secondary endpoints, including pathological complete response (pCR) and major pathological response (mPR).
Based on these results, the U.S. Food and Drug Administration (FDA) accepted Merck's new supplemental Biologics License Application (sBLA) with a target action date of October 16, 2023, under the Prescription Drug User Fee Act (PDUFA).
BMS announced three-year CheckMate-816 trail results demonstrating the advantage of Opdivo as neoadjuvant therapy in NSCLC patients
Bristol Myers Squibb presented the findings of the three-year follow-up data of the Phase 3 CheckMate -816 trial, showing the advantages of utilizing neoadjuvant Opdivo (nivolumab) plus chemotherapy for patients with resectable non-small cell lung cancer (NSCLC). These benefits extend across various PD-L1 expression levels.
The study revealed that neoadjuvant Opdivo in conjunction with chemotherapy has decreased the disease recurrence rate, progression, or mortality compared to chemotherapy alone, regardless of the patient's PD-L1 expression levels. Furthermore, patients who underwent this combined treatment experienced improvements in pathologic complete response (pCR) and major pathologic response (MPR) when compared to those who received chemotherapy exclusively, both in the PD-L1 ≥1% and <1% patient groups. Notably, the safety profile of the Opdivo-based regimen remained consistent across all PD-L1 subgroups.
With a median follow-up duration of 41.4 months, the exploratory analyses of the CheckMate -816 trial yielded the following key findings:
| Neoadjuvant Opdivo + Chemotherapy | Chemotherapy Alone |
Overall Survival (OS) | | |
PD-L1 Expression ≥1% | 85% | 66% |
PD-L1 Expression <1% | 71% | 60% |
Event-Free Survival (EFS) | | |
PD-L1 Expression ≥1% | 72% | 47% |
PD-L1 Expression <1% | 42% | 39% |
Pathologic Complete Response (pCR) | | |
PD-L1 Expression ≥1% | 32.6% | 2.2% |
PD-L1 Expression <1% | 16.7% | 2.6% |
Major Pathologic Response (MPR) | | |
PD-L1 Expression ≥1% | 44.9% | 5.6% |
Major Pathologic Response (MPR) | 29.5% | 14.3% |
Definitive Surgery | | |
PD-L1 Expression ≥1% | 84% | 74% |
Definitive Surgery | 81% | 77% |
BMS presented efficacy results of the CheckMate-77T trial, demonstrating the efficacy of Opdivo as neoadjuvant therapy in NSCLC patients
Bristol Myers Squibb presented findings from the Phase 3 CheckMate -77T trial, showcasing a promising perioperative strategy for non-small cell lung cancer (NSCLC) patients. Opdivo is evaluated in patients with resectable stage IIA to IIIB NSCLC patients.
This innovative approach combines neoadjuvant Opdivo (nivolumab) with chemotherapy, surgery, and adjuvant Opdivo. The results of this trial demonstrate a remarkable advancement in event-free survival (EFS) for this patient population when compared to neoadjuvant chemotherapy with a placebo, followed by surgery and adjuvant placebo.
| Neoadjuvant Opdivo + Chemotherapy | Neoadjuvant Chemotherapy + Placebo |
Pathologic Complete Response (pCR) | 25.3% | 4.7% |
Major Pathologic Response (MPR) | 35.4% | 12.1% |
Definitive Surgery Rates | 78% | 77% |
Complete Resection Rates | 89% | 90% |
Overall survival was not achieved.
In this significant study, the company's second successful Phase 3 randomized trial employing an immunotherapy-based combination for non-metastatic NSCLC, the perioperative regimen proved to be a statistically significant and clinically meaningful improvement in EFS.
October 17, 2023
BeiGene's Aims to Establish Tislelizumab as Neoadjuvant Therapy for NSCLC with RATIONALE 315 Data
BeiGene's PD-L1 inhibitor, tislelizumab, has exhibited a significant improvement in the pathological response rate and event-free survival when compared to chemotherapy in patients with non-small cell lung cancer (NSCLC).
BeiGene presented data from the Phase 3 RATIONALE 315 trial, illustrating the efficacy of tislelizumab as a neoadjuvant therapy for patients with stage II or IIIA NSCLC. This treatment involves administering the drug in combination with chemotherapy before surgery and as monotherapy following the surgical procedure.
The combination of tislelizumab and chemotherapy demonstrated an impressive pathological response rate of 56.2%, a substantial increase when contrasted with the 15.0% observed in patients who received chemotherapy alone. Notably, 40.7% of patients in the tislelizumab combination group achieved a pathological complete response, while only 5.7% of patients on chemotherapy attained the same outcome.
BeiGene also reported that they have twenty-one registration-enabling clinical trials currently underway across more than thirty countries.