Yidafan (ivonescimab) / Akesobio, Summit Therapeutics - LARVOL DELTA

ASCO 2024: Research Roundup (Cancer Therapy Advisor) - "An update of the CROWN trial revealed 'unprecedented' results in advanced non-small cell lung cancer (NSCLC), according to study presenter Benjamin Solomon, MBBS, PhD...'This PFS observed with first-line lorlatinib corresponds to the longest PFS reported in ALK-positive lung cancer and indeed with any targeted therapy in advanced non-small cell lung cancer,' Dr Solomon said during his presentation."

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Apple: AK112 Plus Platinum-based Chemotherapy for EGFR/ALK/ROS1 Positve NSCLC (clinicaltrials.gov) - P1/2 | N=150 | Not yet recruiting | Sponsor: Hunan Province Tumor Hospital | Initiation date: Apr 2024 ➔ Oct 2024

Trial initiation date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

A Phase 3 Study of AK112 Plus AK117 Versus Pembrolizumab in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma (R/M HNSCC) (clinicaltrials.gov) - P3 | N=510 | Not yet recruiting | Sponsor: Akeso

Combination therapy • Metastases • New P3 trial • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

AK112 Combined With Chemotherapy Versus Durvalumab Combined With Chemotherapy in Advanced Biliary Tract Cancer (clinicaltrials.gov) - P3 | N=682 | Not yet recruiting | Sponsor: Akeso

Metastases • New P3 trial • Biliary Cancer • Biliary Tract Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

Phase III Study of AK112 for NSCLC Patients (clinicaltrials.gov) - P3 | N=420 | Active, not recruiting | Sponsor: Summit Therapeutics | Recruiting ➔ Active, not recruiting

Enrollment closed • Metastases • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Miracle-03: Lvosidenib (AK112) Combined With CapeOX and Radiotherapy in Patients With Unresectable Metastatic MSS-type Colorectal Cancer (clinicaltrials.gov) - P2 | N=36 | Not yet recruiting | Sponsor: Fudan University

Metastases • New P2 trial • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

Evaluation of the safety and efficacy of ivonescimab in combination with ligufalimab as first-line (1L) treatment for PD-L1 positive recurrent/metastasis head and neck squamous cell carcinoma (R/M HNSCC) (ESMO 2024) - P1/2 | "Ivonescimab with or without ligufalimab showed promising anti-tumor activity in pts with PD-L1 positive R/M HNSCC with a favorable safety profile."

Clinical • Combination therapy • IO biomarker • Head and Neck Cancer • Oncology • Oral Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • PD-L1

The efficacy and safety of ivonescimab with or without ligufalimab in combination with FOLFOXIRI as first-line (1L) treatment for metastatic colorectal cancer (mCRC) (ESMO 2024) - P2 | "Background: FOLFOXIRI plus bevacizumab is the standard 1L treatment for mCRC... Ivonescimab with or without ligufalimab in combination with FOLFOXIRI showed promising efficacy and tolerable safety as 1L treatment in pts with mCRC."

Clinical • Combination therapy • IO biomarker • Metastases • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • BRAF • KRAS

The safety and efficacy of ivonescimab in combination with chemotherapy as first-line (1L) treatment for triple-negative breast cancer (TNBC) (ESMO 2024) - P2 | "Pts received ivonescimab at 20 mg/kg Q2W and paclitaxel at 90 mg/m2 or nab-paclitaxel at 100 mg/m2 on the 1st, 8th, and 15th day of each four-week treatment cycle. Ivonescimab in combination with chemotherapy showed promising anti-tumor activity and tolerable safety as 1L treatment of TNBC. Further trials to confirm the results are warranted."

Clinical • Combination therapy • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • PD-L1

Akeso's Ivonescimab plus Chemo in First-Line Triple-negative Breast Cancer Showed Promising Preliminary Efficacy and Good Safety at ESMO 2024 (PRNewswire) - P2 | N=80 | NCT05227664 | Sponsor: Akeso | "As of May 31, 2024, a total of 30 patients with locally advanced unresectable or metastatic TNBC were enrolled...Although the follow-up period is relatively short and the data are not yet mature, the study still demonstrates that the ivonescimab combination regimen demonstrates excellent progression-free survival (PFS) benefits for TNBC patients, with safety consistent with previous ivonescimab-related studies...Ivonescimab combination regimen demonstrated high efficacy in tumor response and disease control, with an objective response rate (ORR) of 72.4% and a disease control rate (DCR) of 100%, including a complete response (CR) rate of 6.9%; Ivonescimab combination regimen showed a promising trend towards improved long-term survival benefits, with a median progression-free survival (PFS) of 9.3 months (6.24 months -NE), and a 6-month PFS rate of 73.3%."

P2 data • Triple Negative Breast Cancer

Kangfang Bio-B (09926.HK)’s new drug has been approved to conduct Phase Ib/II clinical trials in the treatment of advanced malignant tumors in the Mainland (uSMART) - "Kangfang Bio-B (09926.HK) announced that the company's independently developed new tumor immunotherapy drug PD-1/VEGF bispecific antibody (development code AK112) has been approved by the Drug Evaluation Center of the China National Drug Administration (CDE) to conduct a Phase Ib/II clinical study for the treatment of advanced malignant tumors."

New P1/2 trial • Oncology

Frontline Ivonescimab May Further Reduce Progression or Death Risk Versus Keytruda in NSCLC Subset (Cure Today) - "'HARMONI-2 is a well-designed randomized phase 3 study comparing ivonescimab with [Keytruda] in the frontline, PD-L1 TPS [of at least] 1% setting in China,' Dr. John V. Heymach...said. 'For the PD-L1 TPS 1% to 49% group, [Keytruda] monotherapy is approved but would not be the preferred comparator in the U.S. and the rest of the world,' he added, noting that a different study design likely will be required before changes are made to current practices."

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EGFR-mutated NSCLC: A roadmap to treatment sequences. (PubMed, Med) - "Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are the standard of care for the management of EGFR-mutated non-small cell lung cancer. Recent results from the HARMONi-A trial lead to considering ivonescimab-a first-in-class, bispecific antibody targeting PD-1 and VEGF-plus chemotherapy as a new second-line option following third-generation TKIs."

IO biomarker • Journal • Review • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

Akeso Published Ivonescimab plus Ligufalimab as First-Line Treatment for PD-L1-Positive Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma at ESMO 2024 (PRNewswire) - P1b/2 | N=114 | NCT05229497 | Sponsor: Akeso | "The objective response rate (ORR) for ivonescimab monotherapy group is 30%, while the ORR increases to 60% in ivonescimab plus ligufalimab group. The disease control rate (DCR) is 80% for ivonescimab monotherapy group improves to 90% with ligufalimab...The ORR for ivonescimab monotherapy and the combination of ivonescimab plus ligufalimab was to 40% and 65%, respectively. The median progression-free survival (mPFS) for ivonescimab monotherapy group was 5.0 months, with the 6-month PFS rate not yet reached. For the combination with ligufalimab group, the mPFS was 7.1 months, with a 6-month PFS rate of 71.8%. The safety profile of the ivonescimab for first-line treatment of PD-L1-positive R/M HNSCC was manageable, with no treatment-related adverse events (TRAE) leading to drug discontinuation or death in both the ivonescimab monotherapy and the ivonescimab plus ligufalimab groups."

P2 data • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

Akeso Published First-Ever Efficacy Data for PD-1/VEGF Bispecific Antibody Ivonescimab with or without CD47 Antibody plus FOLFOXIRI for mCRC at ESMO 2024 (PRNewswire) - P2 | N=104 | NCT05382442 | Sponsor: Akeso | "As of February 29, 2024, the median follow-up time for the ivonescimab plus ligufalimab combination with FOLFOXIRI group was 9.6 months, and 9.0 months for the ivonescimab plus FOLFOXIRI group...For first-line treatment of MSS/pMMR mCRC with ivonescimab, either alone or in combination with ligufalimab and FOLFOXIRI, the objective response rate (ORR) was 88.2%, and the disease control rate (DCR) was 100%. At a median follow-up of 9.6 months, the median progression-free survival (mPFS) has not yet been reached, with a 9-month PFS rate of 86.2%. In the first-line treatment of MSS/pMMR mCRC with ivonescimab combined with FOLFOXIRI, the ORR was 81.8% and the DCR was 100%. At a median follow-up of 9 months, the median PFS has not yet been reached, with a 9-month PFS rate of 81.4%. Both groups demonstrated acceptable safety profiles, with manageable treatment-related adverse events (TRAEs)."

P2 data • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

Antibodies to watch in 2024. (PubMed, MAbs) - "In this installment, we discuss key details for 16 antibody therapeutics granted a first approval in 2023, as of November 17 (lecanemab (Leqembi), rozanolixizumab (RYSTIGGO), pozelimab (VEOPOZ), mirikizumab (Omvoh), talquetamab (Talvey), elranatamab (Elrexfio), epcoritamab (EPKINLY), glofitamab (COLUMVI), retifanlimab (Zynyz), concizumab (Alhemo), lebrikizumab (EBGLYSS), tafolecimab (SINTBILO), narlumosbart (Jinlitai), zuberitamab (Enrexib), adebrelimab (Arelili), and divozilimab (Ivlizi))...These nearly 50 product candidates include numerous innovative bispecific antibodies, such as odronextamab, ivonescimab, linvoseltamab, zenocutuzumab, and erfonrilimab, and antibody-drug conjugates, such as trastuzumab botidotin, patritumab deruxtecan, datopotamab deruxtecan, and MRG002, as well as a mixture of two immunocytokines (bifikafusp alfa and onfekafusp alfa)...Our analyses indicate that these molecules have approval success rates in the range of 14-32%, with higher rates..."

Journal • Infectious Disease • Novel Coronavirus Disease • Oncology • Respiratory Diseases

Phase 3 Study of Ivonescimab (AK112) vs. Pembrolizumab as First-line Treatment for PD-L1-positive Advanced NSCLC: Primary Analysis of HARMONi-2 (IASLC-WCLC 2024) - "Conclusions : Compared to pembrolizumab, ivonescimab demonstrated a statistically significant and clinically meaningful improvement in PFS in PD-L1 positive NSCLC. The data support ivonescimab monotherapy as a new first-line treatment option for PD-L1 positive aNSCLC pts."

Clinical • IO biomarker • Metastases • P3 data • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • ALK • EGFR • PD-L1

A Phase II Study of Perioperative Ivonescimab Alone or Combined with Chemotherapy in Resectable Non-Small Cell Lung Cancer (IASLC-WCLC 2024) - "Pts received neoadjuvant ivonescimab (20 mg/kg) monotherapy in cohort 1 or ivonescimab (20 mg/kg or 30 mg/kg) plus cisplatin/carboplatin and paclitaxel in cohort 2 once every 3 weeks for 3-4 cycles, followed by surgery and adjuvant ivonescimab once every 3 weeks for up to 16 cycles. Higher rates of MPR and pCR were seen with ivonescimab plus chemotherapy than with ivonescimab alone, with ivonescimab 30 mg/kg plus chemotherapy than 20 mg/kg plus chemotherapy, and with squamous NSCLC than non-squamous NSCLC. The safety profile was manageable, and no TRAEs impeded the surgery."

P2 data • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma

PC02. Press Conference (IASLC-WCLC 2024) - "These sessions are open only to registered media who have been credentialed to cover the meeting. PL02.07 - NeoCOAST-2: Efficacy and Safety of Neoadjuvant Durvalumab (D) + Novel Anticancer Agents + CT and Adjuvant D ± Novel Agents in Resectable NSCLC PL02.08 - Perioperative vs Neoadjuvant Nivolumab for Resectable NSCLC: Patient-Level Data Analysis of CheckMate 77T vs CheckMate 816 PL02.11 - Normalized Membrane Ratio of TROP2 by Quantitative Continuous Scoring is Predictive of Clinical Outcomes in TROPIONLung 01 PL02.14 - Triaging ILST Screening Participants at Program Entry: Comparative Performance of PanCan versus LungRADSv1.1 Protocol PL02.04 - Phase 3 Study of Ivonescimab (AK112) vs Pembrolizumab as First-line Treatment for PD-L1-positive Advanced NSCLC: Interim Analysis of HARMONi-2"

Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • PD-L1

Summit Therapeutics Raises $235 Million (Businesswire) - "Summit Therapeutics Inc...today announced that the Company accepted offers from multiple leading biotech institutional and individual investors to purchase an aggregate of approximately 10.35 million shares of the Company’s common stock at $22.70 per share, the closing price on Wednesday, September 11, 2024, for aggregate gross proceeds to the Company of approximately $235 million. The capital raise was completed without bankers’ fees...Summit intends to use the net proceeds to advance, in part, the clinical development of ivonescimab, including in non-small cell lung cancer and in settings outside of lung cancer by leveraging the data that will be presented at ESMO, which may include, but is not limited to, colorectal cancer, and triple-negative breast cancer, in addition to working capital needs and general corporate purposes."

Financing • Breast Cancer • Colorectal Cancer • Gastrointestinal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer

The world’s first CD47 solid tumor phase III: Kangfang Biopharma AK112+AK117 vs. K drug [Google translation] (bydrug.pharmcube.com) - "On September 11, the Drug Clinical Trial Registration and Information Disclosure Platform showed that Kangfang Biopharma launched a head-to-head Phase III study of AK112 (ivonescimab) combined with AK117 (Lefalimab/Ligufalimab) versus Pembrolizumab (K drug) for the treatment of head and neck squamous cell carcinoma."

New P3 trial • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck

Ivonescimab a new agent for #lungcancer patients ! great news for our patients ! we r improving PFS over pembrolizumab! at #WCLC2024 @IASLC @GO2forLungCancr @LungSummit @LUNGevity @LungCancerRx @lcfamerica @LungCancerEu @ClinicalLung @LungCancerFaces

Hot off the presses HARMONI2 has an HR of 0.51, with median PFS of 11.14 vs 5.82 months…appropriate safety profile…hey oncology friends is ivonescimab going to sneak in as 1st line treatment internationally??? #WCLC2024 #thoraciconcology #LungCancer #MedTwitter

Ivonescimab versus pembrolizumab in PD-L1 positive NSCLC patients. Significant benefit with bispecific antibody. Harmony 2 study. What is the mechanism for enhanced efffect of adding VEGF blockade ?

Ivonescimab: Possible New First-Line Standard in PD-L1-Positive Advanced NSCLC? (Medscape) - "The PFS benefit seen with ivonescimab in HARMONi-2 is 'striking,' and the results 'highlight the potential benefits of combined VEGF and PD-1 blockade together,' said John Heymach, MD...who served as discussant for the study....Although the 'really impressive and clinically meaningful' PFS benefits extended across different subgroups, 'we await the overall survival results and additional studies done outside of China to confirm the benefit seen,' Heymach noted."

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