erfonrilimab (KN046)

P1, N=48, Completed, Peking University | Active, not recruiting --> Completed

In this multicenter phase 2 trial, patients with nonsquamous (non-sq) NSCLC receive pemetrexed, whereas those with sq-NSCLC receive paclitaxel, plus KN046 and carboplatin. These findings indicate that first-line treatment with KN046 and chemotherapy is effective and tolerable in metastatic NSCLC patients, warranting further investigation in a larger phase 3 trial. The trial is registered at ClinicalTrials.gov (NCT04054531).

P2, N=55, Completed, Peking University Cancer Hospital & Institute | Recruiting --> Completed | Trial completion date: May 2023 --> Mar 2024

P2, N=95, Terminated, Jiangsu Alphamab Biopharmaceuticals Co., Ltd | The overall safety of KN046 is good, and no new safety signals have been found. The decision to terminate this study was made due to the adjustment of the sponsor's development strategy.

P3, N=408, Recruiting, Jiangsu Alphamab Biopharmaceuticals Co., Ltd | Active, not recruiting --> Recruiting

P1/2, N=216, Recruiting, Suzhou Kintor Pharmaceutical Inc, | Trial completion date: Sep 2025 --> Dec 2025 | Trial primary completion date: Sep 2024 --> Apr 2025

Patients tolerated well the combination therapy. In general, KN046 combined with nab-paclitaxel showed favorable efficacy and survival benefits with tolerable toxicity in the first-line treatment of metastatic TNBC, especially PD-L1 positive, which is worth further investigation.

68Ga-FAPI PET/CT imaging is powerful in assessing tumor immunity and response to immunotherapy in metastatic CRC. This study supports future clinical application of 68Ga-FAPI PET/CT to guide CRC patients for precise TGF-β inhibition plus immunotherapy, recommending 68Ga-FAPI and 18F-FDG dual PET/CT for CRC management.

P1/2, N=41, Recruiting, Shanghai Zhongshan Hospital | Not yet recruiting --> Recruiting | Phase classification: P2 --> P1/2 | Initiation date: Jul 2023 --> Oct 2023

P2, N=39, Recruiting, Peking University Cancer Hospital & Institute

P2, N=18, Not yet recruiting, Peking University

P2, N=98, Recruiting, Peking University Cancer Hospital & Institute | Not yet recruiting --> Recruiting

P2, N=80, Not yet recruiting, Peking University Cancer Hospital & Institute

P2, N=98, Not yet recruiting, Peking University Cancer Hospital & Institute

Both 3 mg/kg and 5 mg/kg KN046 showed promising efficacy and favourable safety profile for advanced NSCLC after failure or intolerance to previous platinum-based chemotherapy.

8 patients experienced ≥ grade 3 irAE, 7 (15.2%) patients discontinued study treatment due to TRAE, but there was no death event related with KN046. Conclusions KN046 demonstrated promising antitumor activity and acceptable toxicity in thymic carcinoma patients who have received at least one line of chemotherapy.

Conclusions KN046 was well tolerated and demonstrated encouraging OS benefit in NSCLC patients who had failed prior ICI(s) therapy. Further study is warranted to confirm the clinical results.

All subjects enrolled received KN046 5 mg/kg Q3W combined with chemotherapy (Pemetrexed, 500 mg/m2, Q3W and carboplatin AUC5, Q3W), until disease progression, intolerable toxicity and other discontinuation criteria. Conclusions KN046 demonstrated encouraging OS benefit and a favorable safety profile in advanced NSCLC with EGFR sensitivity mutation who progressed after EGFR-TKI(s). Further study is warranted to confirm the clinical results.

P1a/1b, N=139, Completed, Jiangsu Alphamab Biopharmaceuticals Co., Ltd | Recruiting --> Completed | N=285 --> 139 | Trial completion date: Oct 2022 --> Feb 2023 | Trial primary completion date: Jan 2022 --> Jan 2023

P1/2, N=52, Completed, Jiangsu Alphamab Biopharmaceuticals Co., Ltd | Active, not recruiting --> Completed | Trial completion date: Sep 2023 --> Oct 2022

KN046 was well tolerated and showed promising antitumor efficacy in advanced solid tumors, especially in patients with NPC. The combination of both CD8 and PD-L1 expression improved the prediction of KN046 response.

P3, N=408, Active, not recruiting, Jiangsu Alphamab Biopharmaceuticals Co., Ltd | Recruiting --> Active, not recruiting

P2, N=41, Not yet recruiting, Shanghai Zhongshan Hospital

KN026 combined with KN046 treatment had demonstrated favorable efficacy and safety profile in HER2 positive other solid tumors (non-GC/GEJ and non-BC). Especially very promising efficacy were observed in ≥3 lines HER2 positive CRC. Based on these results, a pivotal study was planned to verify the efficacy and safety of KN026 and KN046 combo.

P1, N=48, Active, not recruiting, Peking University | Recruiting --> Active, not recruiting | N=24 --> 48

P2, N=54, Enrolling by invitation, Jiangsu Alphamab Biopharmaceuticals Co., Ltd | Not yet recruiting --> Enrolling by invitation

Use of low-dose [I] combined with a dual-target immunosuppressant could be exploited to identify the subset of treatment responders but also exhibited great potential for enhancing antitumor immune responses.

Background: Despite recent FDA approval of immune checkpoint inhibitor pembrolizumab and drug-antibody conjugate in the treatment of mTNBC, the overall survival benefit of these patients remains modest. The combination therapy of KN046 plus nab-paclitaxel has shown favorable clinical efficacy in mTNBC, especially in PD-L1 positive patients. By the cut-off date, the mOS is not mature and there is still more than half of pts alive, which demonstrated an encouraging 2- year OS rate. Pts in this trial tolerated well to the combination therapy and safety profile was manageable.

All subjects enrolled will receive KN046 5 mg/kg Q3W combined with chemotherapy (Pemetrexed, 500 mg/m2, Q3W and carboplatin AUC5, Q3W), until disease progression, intolerable toxicity and other discontinuation criteria. The most common TRAEs of grade 3 or higher were infusion reaction (6/26 [23.1%]), decreased platelet cell count (4/26 [15.4%]) and anemia(3/26 [11.5%]), etc. Conclusions The bispecific antibody, KN046 was well tolerated and effective in treatment of advanced NSCLC with EGFR sensitivity mutation who failed prior EGFR-TKIs. Prospective study is needed to validate the clinical outcome.

The most common TRAEs of grade 3 or higher were infusion reaction (7/64 [10.9%]), hepatic dysfunction (3/64 [4.7%]), pneumonia (2/64 [3.1%]), etc. Conclusions The bispecific antibody, KN046 was well tolerated and effective as second line treatment of advanced NSCLC. KN046 showed promising OS benefit in both squamous and non-squamous NSCLC.

Conclusions KN026 combined with KN046 treatment had demonstrated outstanding efficacy and manageable safety in HER2 positive GC/GEJ patients without prior systemic treatment. It might be deserved to plan a randomized study to compare the KN026+KN046 treatment and the standard of care to further confirm the efficacy and safety.

P2, N=54, Not yet recruiting, Jiangsu Alphamab Biopharmaceuticals Co., Ltd

KN046+Lenvatinib demonstrated a promising efficacy in ORR and PFS and the manageable safety profile in the first-line advanced unresectable or metastatic HCC treatment. These result support the KN046 plus Lenvatinib as a potential new treatment option for this population.

P1, N=24, Recruiting, Peking University | Trial completion date: Dec 2020 --> Dec 2023 | Trial primary completion date: Dec 2020 --> Dec 2022

This chemotherapy-free regimen of KN046 in combination with KN026 has shown promising clinical efficacy and manageable toxicity in HER2-positive non-breast and non-gastric solid tumors with ≥ 1 line prior systemic therapy.The trial is currently ongoing. ClinicalTrials.gov Number, NCT04521179

P1/2, N=216, Recruiting, Suzhou Kintor Pharmaceutical Inc, | Not yet recruiting --> Recruiting

Here we reported the preliminary results from an ongoing phase II trial assessing the safety and efficacy for KN046 (a bispecific antibody blocks both PD-L1 interaction with PD-1/CD80 and CTLA-4 interaction with CD80/CD86) in combination with KN026 (a bispecific antibody that binds to two different HER2 epitopes shared by trastuzumab and pertuzumab) in HER2-positive metastatic breast cancer patients, who have progressed after prior anti-HER2 combinational therapies. The combination of KN046 and KN026, as a chemo free regimen, has shown favorable clinical efficacy with manageable side effects in heavily pre-treated patients with metastatic HER2-positive breast cancer. This trial is currently ongoing. ClinicalTrials.gov number, NCT04521179.

P1/2, N=216, Not yet recruiting, Suzhou Kintor Pharmaceutical Inc,

KN026 combined with KN046 as a chemo-free regimen was safe and demonstrated potential superior clinical benefit to available standard of care in both treatment-naïve and heavily pretreated HER2-postive gastrointestinal tumors. Pivotal trials in HER2-positive GC/GEJ are planned.

Here, we report from a cohort of systemic therapy naive NSCLC pts with resistant oncogenic driver alterations. Patients (pts) with systemic treatment naive, stage IV NSCLC harboring a driver oncogenic alteration were enrolled and received KN046 at 5mg/kg Q3W in combination with 4 cycles’ pemetrexed (500 mg/m2, for non-squamous NSCLC) or paclitaxel (175 mg/m2, for squamous NSCLC) and carboplatin (area under the curve 5 mg/m2) until progressive disease, unacceptable toxicity, withdrawal of informed consent or death. KN046 combined with platinum-based chemotherapy is well tolerated and has demonstrated promising, albeit preliminary anti-tumor activity as 1L treatment for stage IV NSCLC pts with resistant oncogenic driver alterations (including EGFR and HER2 exon 20 insertion mutation, EGFR amplification, RET fusion).

Background: In IMbrave 150 study combo treatment of PD-L1 inhibitor (Atezolizumab) with VEGFR inhibitor（Bevacizumab）prolonged the overall survival dramatically in HCC. KN046+Lenvatinib showed promising antitumor activity with relatively high ORR and a tolerable safety profile in 1st line HCC treatment.

KN046 combined with nab-paclitaxel is well tolerated and has shown favorable clinical efficacy in PD-L1 positive TNBC. Preliminary overall survival data is encouraging. Clinical trial information: NCT03872791