Ten Late-Breaking Abstracts with Positive Results Announced Ahead of 2023 ESMO Congress

Oct 09, 2023 07:37 CST Updated 07:37

AstraZeneca

Biopharmaceutical Manufacturer

Bristol-Myers Squibb

Biopharmaceutical and Nutritional Product R&D and Sales

Roche

Oncology Drug Research, Development, and Manufacturing

MSD

Pharmaceutical R&D and Manufacturer

Eli Lilly

Global Pharmaceutical R&D and Production Company

Seagen

Monoclonal Antibody Developer

Genmab

Differentiated Antibody Therapy Developer

Johnson & Johnson

Healthcare Product Manufacturers, Health Service Providers

Novartis

Drug Development and Manufacturing

The 2023 ESMO Annual Meeting is set to take place from October 20 to 24 in Madrid, Spain. The official website has already released the detailed agenda, LBA.（late-breaking abstracts）Naturally, it is the focus of everyone's attention. Before the official release of specific data, corporate news announcements will disclose in advance whether some important clinical studies have met the primary and/or secondary endpoints. Here, Mofang has compiled a list of 10 LBAs that have officially announced positive results and are worth noting.

1. LBA73——MATTERHORN‍‍

Pathological complete response (pCR) to durvalumab plus 5-fluorouracil, leucovorin, oxaliplatin and docetaxel (FLOT) in resectable gastric and gastroesophageal junction cancer (GC/GEJC): interim results of the global, Phase 3 MATTERHORN study

On June 2, 2023, AstraZeneca announced positive results from the interim analysis of the Phase III MATTERHORN trial. The study showed that in patients with early and locally advanced (Stage II, III, IVA) gastric cancer and adenocarcinoma of the gastroesophageal junction (GEJ), durvalumab combined with chemotherapy demonstrated statistically significant and clinically meaningful improvement in the key secondary endpoint of pathological complete response (pCR), compared to neoadjuvant chemotherapy FLOT (fluorouracil, leucovorin, oxaliplatin, docetaxel) alone.

MATTERHORN is a randomized, double-blind, placebo-controlled, multi-center, global Phase III trial designed to evaluateDurvalumabEfficacy in the perioperative treatment of patients with resectable stage II-IVA gastric cancer and gastroesophageal junction cancer. In this trial, 948 patients were randomly assigned to receive either 1500 mg of durvalumab combined with FLOT or placebo combined with FLOT every 4 weeks preoperatively for two cycles; followed by durvalumab or placebo every 4 weeks; with up to 12 cycles of postoperative treatment (including two cycles of durvalumab or placebo combined with FLOT, and 10 cycles of durvalumab or placebo monotherapy).The primary endpoint of the study is EFS, with key secondary endpoints including pCR and OS.

2. LBA1 - CheckMate 77T

CheckMate 77T：Phase 3 study comparing neoadjuvant nivolumab (NIVO) plus chemotherapy (chemo) vs neoadjuvant placebo plus chemo followed by surgery and adjuvant NIVO or placebo for previously untreated, resectable stage II–IIIB NSCLC.

On September 22, 2023, Bristol-Myers Squibb announced that the Phase III study CheckMate-77T met its primary endpoint assessed by Blinded Independent Central Review (BICR), demonstrating improved event-free survival (EFS) in patients with resectable non-small cell lung cancer (NSCLC) at stages IIA to IIIB. In a pre-specified interim analysis, the perioperative regimen of neoadjuvant nivolumab combined with chemotherapy, followed by surgery and adjuvant nivolumab therapy, showed statistically significant and clinically meaningful improvement in EFS compared to neoadjuvant chemotherapy plus placebo, sequential surgery, and placebo as adjuvant treatment. The primary endpoint of the study was EFS; secondary endpoints included OS, pCR, and major pathologic response (MPR).

3. LBA2 - ALINA

ALINA：efficacy and safety of adjuvant alectinib versus chemotherapy in patients with early-stage ALK+ non-small cell lung cancer (NSCLC)

On September 1, 2023, Roche announced that the Phase III study ALINA of alectinib in treating ALK-positive early-stage NSCLC had met its primary endpoint of disease-free survival (DFS) in a pre-specified interim analysis. The results showed that compared with the platinum-based chemotherapy group, using alectinib as adjuvant therapy for completely resected Stage IB to IIIA ALK-positive NSCLC patients could reduce the risk of disease recurrence and death. At the time of this analysis, OS was not yet mature.

4. LBA21 - KEYNOTE-756

KEYNOTE-756：Phase 3 study of neoadjuvant pembrolizumab (pembro) or placebo (pbo) + chemotherapy (chemo), followed by adjuvant pembro or pbo + endocrine therapy (ET) for early-stage high-risk ER+/HER2– breast cancer

On July 28, 2023, MSD announced that in the pivotal Phase III neoadjuvant/adjuvant study (KEYNOTE-756) conducted in high-risk, early-stage ER+/HER2- breast cancer patients, the combination regimen of pembrolizumab with chemotherapy achieved one of the dual primary endpoints, pCR rate. The trial will continue without changes to the study design to evaluate the other primary endpoint, EFS.

KEYNOTE-756 is a randomized, double-blind Phase III clinical trial designed to evaluatePembrolizumabCombination chemotherapy as neoadjuvant therapy, followed byPembrolizumabEfficacy and Safety of Combined Endocrine Therapy as Adjuvant Treatment for High-Risk, Early-Stage ER+/HER2- Breast Cancer Patients. The dual primary endpoints are pCR rate and EFS, with key secondary endpoints including OS and safety.

5. LBA38——ENGOT-cx11/GOG-3047/KEYNOTE-A18

Pembrolizumab plus chemoradiotherapy for high-risk locally advanced cervical cancer: A randomized, double-blind, phase 3 ENGOT-cx11/GOG-3047/KEYNOTE-A18 study

On July 19, 2023, MSD announced that the supplemental Biologics License Application (sBLA) for Pembrolizumab (Keytruda) has been granted Priority Review by the FDA. The indication is for the treatment of newly diagnosed high-risk locally advanced cervical cancer patients in combination with concurrent chemoradiotherapy.This sBLA is primarily based on the positive results of the Phase III KEYNOTE-A18 study.

This study is a randomized, double-blind, parallel-controlled Phase III clinical trial, enrolling a total of 1060 previously untreated patients with high-risk (lymph node-positive Stage IB2-IIB or Stage III-IVA) locally advanced cervical cancer. It aims to evaluate the efficacy and safety of pembrolizumab combined with concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone. The primary endpoints of the study are PFS and OS. The results showed that the study met its primary endpoint for PFS. OS also demonstrated a trend toward extension, although the data are not yet mature.

6. LBA4 - LIBRETTO-431

Randomized Phase 3 Study of First-line Selpercatinib versus Chemotherapy and Pembrolizumab in RET Fusion-positive NSCLC

On August 4, 2023, Eli Lilly announced the results of the LIBRETTO-431 study, which evaluated the efficacy of selpercatinib (Retevmo) versus pemetrexed plus platinum-based chemotherapy (with or without pembrolizumab) as a first-line treatment for patients with RET fusion-positive advanced or metastatic NSCLC. The study met its primary endpoint, demonstrating a statistically significant and clinically meaningful improvement in PFS with selpercatinib compared to the control group. LIBRETTO-431 is the first randomized study to compare the safety and efficacy of targeted therapy versus PD-1 inhibitor plus chemotherapy in a specific genomic biomarker patient population.

7. LBA7——CheckMate 901

Nivolumab plus gemcitabine-cisplatin versus gemcitabine-cisplatin alone for previously untreated unresectable or metastatic urothelial carcinoma: results from the phase 3 CheckMate 901 trial

On July 11, 2023, Bristol-Myers Squibb (BMS) announced that the sub-study of the Phase III CheckMate-901 trial met the dual primary endpoints of OS and PFS assessed by BICR in the final analysis.

CheckMate-901 is a randomized, open-label, Phase III clinical trial in previously untreated patients with unresectable or metastatic urothelial carcinoma (UC), aiming to evaluate the efficacy and safety of nivolumab + ipilimumab (primary study) or nivolumab + chemotherapy (sub-study) versus standard chemotherapy. The primary endpoints of the primary study include: overall survival (OS) in patients ineligible for cisplatin-based chemotherapy, and OS in patients with tumor cell PD-L1 expression ≥1%. Key secondary endpoints include: OS, PFS, and safety in all randomized patients. The primary endpoints of the sub-study include OS and PFS.

The results of this sub-study showed that for patients with unresectable or metastatic UC who are eligible for cisplatin chemotherapy, compared with standard chemotherapy as first-line treatment,NivolumabAfter combined chemotherapyNivolumabMonotherapy demonstrated statistically significant benefits in OS and PFS. As early as May 16, 2022, BMS announced the primary study results, showing that compared with chemotherapy, the combination of O+Y failed to improve OS in patients with tumor cell PD-L1 expression ≥1%. However, at that time, the data had not been unblinded yet, and the Independent Data Monitoring Committee (IDMC) recommended the trial to continue for the evaluation of other primary and secondary endpoints. In this press release, BMS stated that the primary study is still ongoing.

8. LBA9 - innovaTV 301/ENGOT-cx12/GOG-3057

innovaTV 301/ENGOT-cx12/GOG-3057：A Global, Randomized, Open-Label, Phase 3 Study of Tisotumab Vedotin vs Investigator’s Choice of Chemotherapy in 2L or 3L Recurrent or Metastatic Cervical Cancer

On September 4, 2023, Seagen and Genmab jointly announced that the global Phase III clinical study innovaTV 301 met its primary endpoint of OS. The study results showed that, in patients with recurrent or metastatic cervical cancer whose disease progressed during or after first-line treatment, OS was significantly improved in those receiving tisotumab vedotin (an ADC drug) compared to chemotherapy alone. The Independent Data Monitoring Committee confirmed at the interim analysis that OS exceeded the pre-specified efficacy threshold. Additionally, key secondary endpoints assessed by investigators, such as PFS and ORR, were also statistically significant.

innovaTV 301/ENGOT cx-12/GOG 3057 is a global, randomized, open-label Phase III clinical trial that complements the results of the innovaTV 204 study. Previously, based on the positive results of the innovaTV 204 study, the United States granted accelerated approval (AA) fortisotumab vedotinMarketing Application(Note: September 20, 2021), for the treatment of adult patients with recurrent or metastatic cervical cancer whose disease has progressed during or after first-line chemotherapy. The results of the innovaTV 301 study will serve as the pivotal confirmatory study for U.S. accelerated approval. Zai Lab has initiated the innovaTV 301 extension study in China and is continuing to enroll patients. This is the first approved ADC drug for cervical cancer.

9. LBA14——MARIPOSA

Amivantamab Plus Lazertinib vs Osimertinib as First-line Treatment in Patients With EGFR-mutated, Advanced Non-small Cell Lung Cancer (NSCLC): Primary Results From MARIPOSA, a Phase 3, Global, Randomized, Controlled Trial

On September 28, 2023, Johnson & Johnson announced positive data from the Phase III MARIPOSA study evaluating Rybrevant (amivantamab), an EGFR/c-MET bispecific antibody, in combination with the third-generation EGFR inhibitor Lazertinib versus osimertinib as a first-line treatment for patients with EGFR-mutated locally advanced or metastatic NSCLC. The results showed that the MARIPOSA study met its primary endpoint, demonstrating superiority compared to the osimertinib group.amivantamab + Patients in the Lazertinib treatment group experienced a statistically significant and clinically meaningful improvement in PFS. Additionally, the interim analysis showed that the combination therapy group also demonstrated a trend toward OS benefit. Johnson & Johnson also announced this month.amivantamabThe Phase III MARIPOSA-2 Study of Lazertinib in Combination with Chemotherapy vs. Chemotherapy Alone in Osimertinib-Resistant Patients Met its Primary Endpoint of PFS.

10. LBA13——PSMAfore

Phase 3 trial of [177Lu]Lu-PSMA-617 in taxane-naive patients with metastatic castration-resistant prostate cancer (PSMAfore)

On December 5, 2022, Novartis announced that the pivotal Phase III PSMAfore study of Pluvicto [lutetium (177Lu) vipivotide tetraxetan], a PSMA-targeted nuclear radioligand therapy for the treatment of patients with PSMA-positive metastatic castration-resistant prostate cancer (mCRPC), met its primary endpoint. In mCRPC patients who were previously treated with an androgen receptor pathway inhibitor (ARPI) and were PSMA-positive, treatment with Pluvicto demonstrated a statistically significant and clinically meaningful improvement in radiographic progression-free survival (rPFS) compared to switching to another ARPI. This suggests that Pluvicto can also provide clinical benefit to mCRPC patients who have not received taxane-based chemotherapy.

The VISION study had previously validated the efficacy of Pluvicto in the treatment of advanced prostate cancer. The VISION study indicated that, in patients with mCRPC who were PSMA-positive and had previously received ARPI and taxane-based chemotherapy, the risk of death was significantly reduced in the group receiving Pluvicto combined with standard treatment compared to the standard treatment alone group.

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