3 Key Takeaways
Plain English Summary- 01Core Finding
Primary outcomes were safety/tolerability and recommended Phase 2 dose (RP2D) in Phase 1 and anti-tumor activity in Phase 2.
- 02Study Evidence
Tested in a early human trial (n = 34) at the Phase I/II stage.
- 03Practical Meaning
Integrated analyses from safety, pharmacokinetic, pharmacodynamic and preliminary anti-tumor data supported the selection of 0.08 mg kg -1 as the RP2D.
What This Means for You
Invika selectively and potently expanded peripheral and intratumoral Vβ6/Vβ10 T cells, of a predominantly memory-like phenotype, dose-dependently, peaking at the OBDs. Pharmacodynamic increases in interferon (an immune-signaling protein)-γ and soluble CD25 followed a similar pattern.
Integrated analyses from safety, pharmacokinetic, pharmacodynamic and preliminary anti-tumor data supported the selection of 0.08 mg kg -1 as the RP2D. In conclusion, Phase 1 of START-001 met its primary outcomes by demonstrating the acceptable safety profile of invika consistent with its mechanism of action and selecting an RP2D.
Initial Phase 2 results further corroborated the safety of invika and expanded its preliminary evidence of clinically meaningful anti-tumor activity in ICB-resistant solid tumors, supporting further evaluation in the ongoing Phase 2. .
The Discovery
Invikafusp alfa (invika), a first-in-class, bispecific, dual T cell agonistic antibody selectively targeting Vβ6/Vβ10 T cell subsets, is being evaluated in START-001, a multicenter Phase 1/2 monotherapy trial in participants with mostly immune checkpoint blockade (ICB)-resistant, antigen-rich solid tumors. Primary outcomes were safety/tolerability and recommended Phase 2 dose (RP2D) in Phase 1 and anti-tumor activity in Phase 2. As of 12 March 2025, Phase 1 completed dose escalation (n = 34) through dose levels of 0.01, 0.02, 0.04, 0.08, 0.12 and 0.16 mg kg -1 without reaching maximum tolerated dose, and initial Phase 2 enrolled 18 participants. Two participants experienced reversible dose-limiting toxicities, one at each of the 0.08 mg kg -1 and 0.16 mg kg -1 dose levels. The most common treatment-related adverse event was cytokine release syndrome, mainly grades 1 and 2. No treatment-related deaths or non-laboratory grade 4 adverse events were reported. At the optimal biological doses (OBDs; 0.08 mg kg -1 and 0.12 mg kg -1 ) in combined Phase 1 and Phase 2 cohorts, the overall objective response rate was a clinically meaningful level (4/27), including confirmed partial responses in immunologically cold tumors, such as microsatellite stable colorectal cancer and programmed death-ligand 1 (PD-L1)-negative non-small cell lung cancer. No objective responses were seen at doses lower than 0.08 mg kg -1.
How It Works, Simply
This oncology research focuses on antibodies · T cells · Immune response. Researchers evaluated it using an early human trial (n = 34) at the Phase I/II stage of medical research.
3 Key Takeaways
Clinical Takeaways- 01Core Finding
Primary outcomes were safety/tolerability and recommended Phase 2 dose (RP2D) in Phase 1 and anti-tumor activity in Phase 2.
- 02Study Evidence
Tested in a early human trial (n = 34) at the Phase I/II stage.
- 03Practical Meaning
Integrated analyses from safety, pharmacokinetic, pharmacodynamic and preliminary anti-tumor data supported the selection of 0.08 mg kg -1 as the RP2D.
Key Numbers
Biological Mechanism & Study Design
Study Design & Cohort
Early human trial
Early human trial (n = 34) · Phase I/II
Biological Pathway & Modality
Antibodies · T cells · Immune response
Intervention: Bispecific dual T cell agonist
Experimental Findings & Endpoints
Invikafusp alfa (invika), a first-in-class, bispecific, dual T cell agonistic antibody selectively targeting Vβ6/Vβ10 T cell subsets, is being evaluated in START-001, a multicenter Phase 1/2 monotherapy trial in participants with mostly immune checkpoint blockade (ICB)-resistant, antigen-rich solid tumors.
Primary outcomes were safety/tolerability and recommended Phase 2 dose (RP2D) in Phase 1 and anti-tumor activity in Phase 2. As of 12 March 2025, Phase 1 completed dose escalation (n = 34) through dose levels of 0.01, 0.02, 0.04, 0.08, 0.12 and 0.16 mg kg -1 without reaching maximum tolerated dose, and initial Phase 2 enrolled 18 participants.
Two participants experienced reversible dose-limiting toxicities, one at each of the 0.08 mg kg -1 and 0.16 mg kg -1 dose levels. The most common treatment-related adverse event was cytokine release syndrome, mainly grades 1 and 2.
No treatment-related deaths or non-laboratory grade 4 adverse events were reported. At the optimal biological doses (OBDs; 0.08 mg kg -1 and 0.12 mg kg -1 ) in combined Phase 1 and Phase 2 cohorts, the overall objective response rate was a clinically meaningful level (4/27), including confirmed partial responses in immunologically cold tumors, such as microsatellite stable colorectal cancer and programmed death-ligand 1 (PD-L1)-negative non-small cell lung cancer.
No objective responses were seen at doses lower than 0.08 mg kg -1.
Clinical Translation & Practice Context
Invika selectively and potently expanded peripheral and intratumoral Vβ6/Vβ10 T cells, of a predominantly memory-like phenotype, dose-dependently, peaking at the OBDs.
Pharmacodynamic increases in interferon-γ and soluble CD25 followed a similar pattern.
Integrated analyses from safety, pharmacokinetic, pharmacodynamic and preliminary anti-tumor data supported the selection of 0.08 mg kg -1 as the RP2D. In conclusion, Phase 1 of START-001 met its primary outcomes by demonstrating the acceptable safety profile of invika consistent with its mechanism of action and selecting an RP2D.
Initial Phase 2 results further corroborated the safety of invika and expanded its preliminary evidence of clinically meaningful anti-tumor activity in ICB-resistant solid tumors, supporting further evaluation in the ongoing Phase 2. .
The Bottom Line · Clinical Pearl
“Initial Phase 2 results further corroborated the safety of invika and expanded its preliminary evidence of clinically meaningful anti-tumor activity in ICB-resistant solid tumors, supporting further evaluation in the ongoing Phase 2. .”
Published in Nature Medicine · Current Stage: Phase I/II