Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as AK112, Ivonescimab Injection, AK112 Injection, Ivonescimab Dose 1, Ivonescimab RP3D, SMT112
Ivonescimab · 16 trials · 30 indications
the time from the date of randomization to the date of death from any cause. Patients still alive at the time of analysis will be censored at the date of their last known alive date
Progression-free survival (PFS) assessed by IRRC per RECIST v1.1
Progression-free survival (PFS) assessed by IRC per RECIST v1.1 in the ITT population.
ORR was defined as the percentage of participants achieving complete response (CR) and partial response (PR) on treatment based on RECIST v1.1 criteria.
Time interval between the date of randomization and the date of intracranial progression or neurological related death, whichever occurs first
The objective response rate is defined as the percentage of patients with a complete response (CR) or a partial response (PR) for a given treatment
Overall Response Rate (ORR) defined as the proportion of participants achieving complete response (CR) or partial response (PR) as best response on treatment based on RECIST v1.1 criteria at each dose level.
All grade 3-5 adverse events (AE) with treatment attribution of possibly, probably or definite based on Common Terminology Criteria for Adverse Events Version 5.0 (CTCAE V5.0) that are not resolved in accordance with treatment guidelines will be counted. Rate is the proportion of treated participants experiencing at least one of these adverse events as defined during the time of observation.
The analysis of the primary efficacy endpoint will be conducted in all eligible patients, based on the disease control rate (DCR) at 12 weeks according to mRECIST 1.1 for mesothelioma, which was defined as the proportion of patients with compete response (CR), partial response (PR) or stable disease (SD) at 12 weeks as assessed by the independent review committtee.
ORR is the proportion of subjects with complete response(CR) or partial response(PR) , based on RECIST v1.1
An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment.
Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0
Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0
Adverse events (AEs) as characterized by type, incidence, severity, seriousness, and relationship to study treatment
PFS per RECIST v1.1 by Independent Radiology Review Committee (IRRC)
| Arm | Type | Description |
|---|---|---|
| Bras A: Ivonescimab | EXPERIMENTAL | Ivonescimab (10 mg/kg iv, 60 min ± 10 min infusion, Q3W) |
| Bras B: Ivonescimab - Ligufalimab | EXPERIMENTAL | Ivonescimab (10 mg/kg iv, 60 min ± 10 min infusion, Q3W), and ligufalimab (45 mg/kg iv, 120 min ± 15 min infusion, Q3W). |
| Bras C: Pembrolizumab | ACTIVE_COMPARATOR | Pembrolizumab (200 mg iv, 60 min ± 10 min infusion, Q3W). |
| Arm A: Ivonescimab in combination with mFOLFOX6 | EXPERIMENTAL | Subjects will receive Ivonescimab Plus mFOLFOX6 via intravenous infusion (IV) Q2W, up to 8 cycles. Afterward, Ivonescimab plus Leucovorin and 5-FU will be used for maintenance treatment (administered on Day 1 of each cycle, Q2W) up to 2 years. |
| Arm B: Bevacizumab in combination with mFOLFOX6 | ACTIVE_COMPARATOR | Subjects will receive bevacizumab Plus mFOLFOX6 (Oxaliplatin, Leucovorin and 5-Fluorouracil) via intravenous infusion (IV) Q2W, up to 8 cycles in treatment periods per the randomization schedule. Afterward, bevacizumab Plus 5-FU and Leucovorin will be used for maintenance treatment (administered on Day 1 of each cycle, Q2W) up to 2 years. |
| Arm A - Ivonescimab | EXPERIMENTAL | Subject will receive ivonescimab as an IV injection |
| Arm B - Pembrolizumab | ACTIVE_COMPARATOR | Subject will receive pembrolizumab as an IV injection |
| Arm A - Ivonescimab and chemotherapy | EXPERIMENTAL | Subject will receive ivonescimab and chemotherapy |
| Arm B - Pembrolizumab and chemotherapy | ACTIVE_COMPARATOR | Subject will receive pembrolizumab and chemotherapy |
| AK112 in combination with Pemetrexed and Carboplatin | EXPERIMENTAL | Subjects will receive AK112 Plus Pemetrexed and Carboplatin via intravenous infusion (IV) Q3W, up to 4 cycles. Afterward, AK112 Plus Pemetrexed will be used for maintenance treatment (administered on Day 1 of each cycle, Q3W) up to 2 years. |
| Placebo in combination with Pemetrexed and Carboplatin | ACTIVE_COMPARATOR | Subjects will receive Placebo Plus Pemetrexed and Carboplatin via intravenous infusion (IV) Q3W, up to 4 cycles in treatment periods per the randomization schedule. Afterward, Placebo Plus Pemetrexed will be used for maintenance treatment (administered on Day 1 of each cycle, Q3W) up to 2 years. |
| Cohort 1: Adenoid Cystic Carcinoma | EXPERIMENTAL | Approximately 11 participants will be enrolled to this cohort in the first stage of recruitment. If there are ≤2 participants (out of 22) with responses to the therapy, the accrual to the study will be stopped. If there are \>2 participants with response, accrual will continue. Enrolled participants will complete: * Baseline visit * Imaging tests every 9 weeks * Cycle 1 through End of Treatment (21 day cycles) --Day 1: Predetermined dose of Ivonescimab 1x daily. * End of treatment visit with imaging * Follow up: every 12 weeks |
| Cohort 2: Non-Adenoid Cystic Carcinoma Salivary Gland Carcinoma | EXPERIMENTAL | Approximately 11 participants will be enrolled to this cohort in the first stage of recruitment. If there are ≤2 participants (out of 22) with responses to the therapy, the accrual to the study will be stopped. If there are \>2 participants with response, accrual will continue. Enrolled participants will complete: * Baseline visit * Imaging tests every 9 weeks * Cycle 1 through End of Treatment (21 day cycles) --Day 1: Predetermined dose of Ivonescimab 1x daily. * End of treatment visit with imaging * Follow up: every 12 weeks |
| Sequencing arm | EXPERIMENTAL | Patients will receive SRS/FSRT for all BM within ≤14 days from randomization, followed by 4 cycles of platinum-based chemotherapy combined with ivonescimab at 20 mg/kg every 3 weeks (Q3W). The systemic therapy will be followed by maintenance therapy with ivonescimab at 20 mg/kg plus pemetrexed (for patients with non-squamous NSCLC only) Q3W, for up to 2 years. |
| Systemic treatment alone arm | EXPERIMENTAL | Patients will receive 4 cycles of platinum-based chemotherapy combined with ivonescimab 20 mg/kg Q3W, followed by maintenance ivonescimab 20 mg/kg with pemetrexed (pemetrexed non-squamous only) Q3W for a maximum of 2 years. |
| Experimental | EXPERIMENTAL | Experimental treatment under study |
| Control | ACTIVE_COMPARATOR | Standard of care second-line treatment for advanced biliary tract cancer |
| 1st line | EXPERIMENTAL | FOLFOX combined with Ivonescimab |
| 2nd line | EXPERIMENTAL | Paclitaxel or Irinotecan (at investigator discretion) combined with ivonescimab |
| Ivonescimab + FOLFIRI | EXPERIMENTAL | Ivonescimab 20 mg/kg by intravenous infusion (IV) once every 2 weeks (Q2W) combined with FOLFIRI chemotherapy (irinotecan 180 mg/m2 IV, folinic acid 400 mg/m2 IV (or L-folinic acid 200 mg/m²), and fluorouracil (5-FU) 400 mg/m² IV bolus; followed by 5 FU 2400 mg/m2 as a 46 hour continuous IV infusion), every two weeks |
| Bevacizumab + FOLFIRI | ACTIVE_COMPARATOR | Bevacizumab 5 mg/kg by intravenous infusion (IV) once every 2 weeks (Q2W) combined with FOLFIRI chemotherapy (irinotecan 180 mg/m2 IV, folinic acid 400 mg/m2 IV (or L-folinic acid 200 mg/m²), and fluorouracil (5-FU) 400 mg/m² IV bolus; followed by 5 FU 2400 mg/m2 as a 46 hour continuous IV infusion), every two weeks |
| Arm A: Ivonescimab 10 mg/kg | EXPERIMENTAL | Induction with ivonescimab 10 mg/kg, carboplatin and etoposide every 21 days x 4 cycles followed by maintenance ivonescimab 10 mg/kg every 21 days until progression, unacceptable toxicity or participant withdrawal. Up to 24 months of ivonescimab from cycle 1 day 1 of Induction. |
| Arm B: Ivonescimab 20 mg/kg | EXPERIMENTAL | Induction with ivonescimab 20 mg/kg, carboplatin and etoposide every 21 days x 4 cycles followed by maintenance ivonescimab 20 mg/kg every 21 days until progression, unacceptable toxicity or participant withdrawal. Up to 24 months of ivonescimab from cycle 1 day 1 of Induction. |
| Ivonescimab | EXPERIMENTAL | 20 mg/kg IV (a fixed dose of 3200 mg for ivonescimab should be used for patients with weight ≥160 kg), every 3 weeks. |
| Part 1_Chemotherapy Regimen Selection Stage Group A(AK112+AK117+XELOX) | EXPERIMENTAL | AK112+AK117+XELOX AK112 and AK117 and XELOX(Oxaliplatin 130 mg/sqm iv day 1, Capecitabine via oral, the total daily dose was 2000mg/sqm, day1-14) If no progression occurs during AK112 plus AK117 plus XELOX, patients will receive maintenance capecitabine plus AK112 plus AK117 at the same dose used at the last cycle of the induction treatment. Capecitabine plus AK112 plus AK117 will be repeated every 3 weeks until disease progression, unacceptable toxicity or patient's refusal. |
| Part 1_Chemotherapy Regimen Selection Stage Group B(AK112+AK117+FOLFOXIRI) | EXPERIMENTAL | AK112+AK117+FOLFOXIRI AK112 and AK117 and FOLFOXIRI(Irinotecan 150-165 mg/sqm iv day 1, Oxaliplatin 85 mg/sqm iv day 1, Leucovorin(LV) 400 mg/sqm iv day 1, 5-fluorouracil(5-FU) 2400-2800 mg/sqm 46-48 hours continuous infusion, starting on day 1) If no progression occurs during AK112 plus AK117 plus FOLFOXIRI, patients will receive maintenance 5-FU/LV plus AK112 plus AK117 at the same dose used at the last cycle of the induction treatment. 5-FU/LV plus AK112 plus AK117 will be repeated biweekly until disease progression, unacceptable toxicity or patient's refusal. |
| Part 1_Expansion Stage Group A(AK112 DS1+Chemotherapy) | EXPERIMENTAL | AK112 (Dose1) +Chemotherapy(Decided by Chemotherapy Regimen Selection Stage) AK112 and XELOX or FOLFOXIRI(the same dosage, frequency and duration with Chemotherapy Regimen Selection Stage) |
| Part 1_Expansion Stage Group B(AK112 DS1+AK117 DS1+Chemotherapy) | EXPERIMENTAL | AK112 (Dose1) +AK117 (Dose1) +Chemotherapy(Decided by Chemotherapy Regimen Selection Stage) AK112 and AK117 and XELOX or FOLFOXIRI(the same dosage, frequency and duration with Chemotherapy Regimen Selection Stage) |
| Part 1_Expansion Stage Group C (AK112 DS2+Chemotherapy) | EXPERIMENTAL | AK112 (Dose2)+Chemotherapy(Decided by Chemotherapy Regimen Selection Stage). AK112 and XELOX or FOLFOXIRI(the same dosage, frequency and duration with Chemotherapy Regimen Selection Stage). |
| Part 1_Expansion Stage Group D (AK112 DS2 +AK117 DS2 +Chemotherapy) | EXPERIMENTAL | AK112(Dose2) + AK117(Dose2)+Chemotherapy(Decided by Chemotherapy Regimen Selection Stage) AK112 and AK117 and XELOX or FOLFOXIRI(the same dosage, frequency and duration with Chemotherapy Regimen Selection Stage) |
| Part 1_Expansion Stage Group E (AK112 DS2+AK117 DS1+Chemotherapy) | EXPERIMENTAL | AK112(Dose2)+AK117(Dose1)+Chemotherapy(Decided by Chemotherapy Regimen Selection Stage) AK112 and AK117 and XELOX or FOLFOXIRI(the same dosage, frequency and duration with Chemotherapy Regimen Selection Stage) |
| Part 1_Extension Stage Group F (AK112 DS1 + mFOLFOX6) | EXPERIMENTAL | AK112 (Dose1) +mFOLFOX6 ( Oxaliplatin 85 mg/sqm IV day 1, Leucovorin 400 mg/sqm IV day 1, 5-fluorouracil(5-FU) 2400 mg/sqm 46-48 hours continuous infusion, starting on day 1). If no progression occurs during AK112 plus mFOLFOX6, patients will receive maintenance 5- FU/LV plus AK112 at the same dose used at the last cycle of the induction treatment. 5-FU/LV plus AK112 will be repeated biweekly until disease progression, unacceptable toxicity or patient's refusal. |
| Part 1_Extension Stage Group G (AK112 DS2+mFOLFOX6) | EXPERIMENTAL | AK112 (Dose2) +mFOLFOX6 ( Oxaliplatin 85 mg/sqm IV day 1, Leucovorin 400 mg/sqm IV day 1, 5-fluorouracil(5-FU) 2400 mg/sqm 46-48 hours continuous infusion, starting on day 1) If no progression occurs during AK112 plus mFOLFOX6, patients will receive maintenance 5- FU/LV plus AK112 at the same dose used at the last cycle of the induction treatment. 5-FU/LV plus AK112 will be repeated biweekly until disease progression, unacceptable toxicity or patient's refusal. |
| Part 2 cohort 1(AK112) | EXPERIMENTAL | Subjects receive AK112 until disease progression or unacceptable toxicity AK112 (until disease progression, unacceptable toxicity or patient's refusal) |
| Part 2 cohort 2(AK112+AK117) | EXPERIMENTAL | Subjects receive AK117 and AK112 until disease progression or unacceptable toxicity AK112 and AK117 ( until disease progression, unacceptable toxicity or patient's refusal) |
| Cohort 1 | EXPERIMENTAL | Treatment with Ivonescimab (IV) Q3W For ACC |
| Cohort 2 | EXPERIMENTAL | Treatment with Ivonescimab (IV) Q3W For PPGL Suspended: No |
| PTX + IVO | EXPERIMENTAL | Treatment with Paclitaxel (IP) + Ivonescimab (IV) |
| Phase 2: Arm A | EXPERIMENTAL | Ivonescimab Dose 1 + EV |
| Phase 2: Arm B | EXPERIMENTAL | Ivonescimab Dose 2 + EV |
| Phase 3: Arm 1 | EXPERIMENTAL | Ivonescimab RP3D (recommended Phase 3 dose) + EV |
| Phase 3: Arm 2 | ACTIVE_COMPARATOR | Pembrolizumab 200 mg + EV |
| Name | Type | Description |
|---|---|---|
| Ivonescimab 10 mg/kg | DRUG | Ivonescimab is a humanized immunoglobulin (Ig) G1 monoclonal antibody (mAb) being investigated as a cancer immunotherapy agent. Ivonescimab binds to human VEGF-A which is involved in tumor angiogenesis, and to human PD-1 that is a cell surface receptor expressed primarily on activated T cells and acts to inhibit T cell activation. |
| Ligufalimab | DRUG | AK117 is a humanized IgG4 mAb being investigated as a cancer immunotherapy agent |
| Pembrolizumab (KEYTRUDA ®) | DRUG | Pembrolizumab is a humanized monoclonal antibody (IgG4 kappa isotype with stabilizing sequence alteration in the Fc region) against PD-1 (programmed cell death-1), produced in Chinese hamster ovary cells by recombinant DNA technology. |
| Drug: Ivonescimab Injection | DRUG | Subjects will receive Ivonescimab Plus mFOLFOX6 (Oxaliplatin, Leucovorin and 5-Fluorouracil) via intravenous infusion (IV) Q2W, up to 8 cycles. Afterward, Ivonescimab plus Leucovorin and 5-Fluorouracil will be used for maintenance treatment (administered on Day 1 of each cycle, Q2W) for up to 2 years. |
| Drug: Bevacizumab Injection | DRUG | Subjects will receive bevacizumab Plus mFOLFOX6 (Oxaliplatin, Leucovorin and 5-Fluorouracil) via intravenous infusion (IV) Q2W, up to 8 cycles in treatment periods per the randomization schedule. Afterward, bevacizumab Plus 5-FU and Leucovorin will be used for maintenance treatment (administered on Day 1 of each cycle, Q2W) up to 2 years. |
| Ivonescimab Injection | BIOLOGICAL | Subject will receive ivonescimab as an IV injection |
| Pembrolizumab Injection | BIOLOGICAL | Subject will receive Pembrolizumab as an IV injection |
| AK112 Injection | DRUG | Subjects will receive AK112 Plus Pemetrexed and Carboplatin via intravenous infusion (IV) Q3W, up to 4 cycles. Afterward, AK112 Plus Pemetrexed will be used for maintenance treatment (administered on Day 1 of each cycle, Q3W) up to 2 years. |
| Placebo Injection | DRUG | Subjects will receive Placebo Plus Pemetrexed and Carboplatin via intravenous infusion (IV) Q3W, up to 4 cycles in treatment periods per the randomization schedule. Afterward, Placebo Plus Pemetrexed will be used for maintenance treatment (administered on Day 1 of each cycle, Q3W) up to 2 years. |
| Ivonescimab | DRUG | An immunoglobulin (Ig) G1 monoclonal antibody (mAb), single-use vial, via intravenous (into the vein) infusion per protocol. |
| FOLFOX regimen | DRUG | oxaliplatin 85 mg/m² IV, leucovorin 200 mg/m² IV (or folinic acid 400 mg/m²), and fluorouracil (5-FU) 400 mg/m² IV bolus; followed by 5 FU 2400 mg/m² as a 46 hour continuous IV infusion, every 2 weeks |
| Irinotecan | DRUG | 180 mg/ m2 IV over 90 min infusion every two weeks for a minimum of 4 cycles |
| Paclitaxel | DRUG | 80 mg/m2 IV at D1, D8 and D15, every four weeks (D1=D28) |
| Bevacizumab | DRUG | Bevacizumab 5 mg/kg by intravenous infusion (IV) once every 2 weeks (Q2W) |
| FOLFIRI Protocol | DRUG | FOLFIRI chemotherapy (irinotecan 180 mg/m2 IV, folinic acid 400 mg/m2 IV (or L-folinic acid 200 mg/m²), and fluorouracil (5-FU) 400 mg/m² IV bolus; followed by 5 FU 2400 mg/m2 as a 46 hour continuous IV infusion), every two weeks |
| Ivonescimab 20 mg/kg | DRUG | Induction every 21 days x 4 cycles: Ivonescimab 20 mg/kg IV on Day 1 followed by carboplatin AUC 5 IV on Day 1 and etoposide 100 mg/m² IV on Day 1, 2 and 3 followed by maintenance ivonescimab 20 mg/kg every 21 days until progression, unacceptable toxicity or participant withdrawal. Up to 24 months of ivonescimab from cycle 1 day 1 of Induction. |
| AK112 | DRUG | AK112 via intravenous (IV) infusion until disease progression or unacceptable toxicity |
| AK117 | DRUG | AK117 via intravenous (IV) infusion until disease progression or unacceptable toxicity |
| Oxaliplatin | DRUG | Oxaliplatin via IV infusion |
| Capecitabine | DRUG | Capecitabine via oral,The total daily dose was 2000mg/sqm, Each cycle was administered for 2 consecutive weeks, followed by a week of rest, with a treatment cycle every 21 days |
| Leucovorin | DRUG | Leucovorin via IV infusion |
| 5-fluorouracil | DRUG | 5-fluorouracil via IV infusion |
| IP PTX | DRUG | Given by IP port |
| Ivonescimab Dose 1 | DRUG | First ivonescimab dose to be tested in Phase 2 |
| enfortumab vedotin (EV) | DRUG | Standard of care therapy |
| Pembrolizumab | DRUG | 200 mg |
| Ivonescimab Dose 2 | DRUG | Second Ivonescimab dose to be tested in Phase 2 part of the study |
| Ivonescimab RP3D | DRUG | Recommended Phase 3 dose of Ivonescimab after Phase 2 data analysis |
Inclusion Criteria: 1. Patient capable of voluntary giving her/his written informed consent. 2. Age ≥ 18 and \< 80 years old at the time of enrolment. 3. Eastern Cooperative Oncology Organization (ECOG) performance status score of 0 or 1. 4. Expected survival ≥ 6 months at randomization. 5. Patient...
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Ivonescimab is an investigational monoclonal antibody being developed by Summit Therapeutics Inc. (ticker SMMT) for the treatment of several types of cancer. It is currently in Phase 2 clinical development and is being studied in solid tumors including non small cell lung cancer, metastatic colorectal cancer, metastatic urothelial carcinoma, and biliary tract cancer.
Ivonescimab is being studied for use in oncology across multiple tumor types, including non small cell lung cancer, extensive stage lung small cell cancer, biliary tract cancer, metastatic colorectal cancer, metastatic esophageal adenocarcinoma, and metastatic urothelial carcinoma. It is investigational and has not been approved for commercial use.
Ivonescimab is developed by Summit Therapeutics Inc., which trades under the ticker SMMT. The company is running Phase 2 clinical trials of the drug in several cancer indications, including metastatic urothelial carcinoma, metastatic colorectal cancer, and adrenocortical carcinoma.
Ivonescimab is in Phase 2 clinical development. All three of its active trials are Phase 2 studies, and none have been completed. The drug is investigational and is not FDA approved; it remains under clinical evaluation for the cancer indications being studied.
Ivonescimab is being evaluated in Phase 2 trials including NCT07815665 in metastatic urothelial carcinoma, NCT07753824 in high-grade metastatic appendiceal adenocarcinoma, NCT07743138 in adrenocortical carcinoma or pheochromocytoma/paraganglioma, and NCT07359456 in metastatic colorectal cancer. These studies are active, with several not yet recruiting.
Yes, Ivonescimab is also known as AK112. Other names used for the same asset include Ivonescimab Injection, AK112 Injection, and Ivonescimab 10 mg/kg. These refer to the same monoclonal antibody developed by Summit Therapeutics Inc. (SMMT).