ASCO 2025: Innovent’s Nuclear Bomb, Instant Explosion

If typical potential first-in-class or best-in-class drugs are considered heavy bombs for pharmaceutical companies, then Innovent’s IBI-363 is a nuclear bomb for Innovent. This time, this nuclear bomb completely exploded at this year’s ASCO conference, with once highly anticipated expectations being well validated by data. Innovent’s recent wave of surge and bubble has been fully realized—this round has made a killing!

IBI-363 Overview

Innovent’s IBI-363 really started to gain hype around mid-last year. IBI-363 significantly activates T cells through a powerful mechanism and enhances the cytotoxic effect of T cells. In addition, it reduces drug toxicity by preferentially binding to IL-2α and decreasing binding to IL-2β and IL-2γ. Today, IBI-363 might be the next generation’s “O drug,” potentially bringing a revolutionary era just like the PD-1 monoclonal antibody’s first-in-class status.

Here is a timeline overview of IBI-363’s data releases.

The first published data was from the 2024 ESMO conference, presenting Phase 1 multi-tumor basket trials. The overall data is shown in the figure. Such basket trials should first focus on the safety of patients across different indications at the same dose. As shown, at a dose of 3mg/kg every 3 weeks (Q3W), the incidence of grade 3 or higher treatment-related adverse events was only 13.2%. If we compare this shoulder-to-shoulder with PD-1/VEGF-type antibodies, this is much better than the latter overall.

In terms of efficacy by indication, IO treatment-failed squamous NSCLC patients receiving the 3mg/kg dose achieved a stunning ORR of 100%, as if this drug was born to target NSCLC.

The surprises don’t stop there; this drug also has unexpected efficacy against previously difficult “cold tumors.” For immune treatment-na?ve mucosal melanoma, a typical cold tumor, the ORR reached an amazing 75%, which has long been a very difficult challenge.

Next was the 2024 WCLC data. As shown, in squamous carcinoma patients, those receiving 3mg/kg showed a significant dose-response effect compared to the 1/1.5mg/kg groups. Moreover, patients in the 3mg/kg group with follow-up beyond 12 weeks already had an ORR of 50%.

For PD-1-related drugs, PD-L1 TPS expression is often a key factor limiting efficacy. IBI-363 also performed well in this regard: among squamous NSCLC patients receiving 1/1.5 mg/kg and 3 mg/kg doses with PD-L1 TPS <1% (n=22) and TPS ≥1% (n=22), ORRs were similar at 36.4% and 31.8%, respectively. This shows that as a “plus” to PD-1 antibodies, IBI-363 might not be as limited by PD-L1 TPS expression as Keytruda, giving it potential as a truly versatile immunotherapy agent.

Then came the 2024 SITC conference, mainly presenting first-line treatment results for melanoma. Among patients with at least one baseline tumor assessment (n=31), the overall ORR was 67.7%. Currently approved first-line immunotherapy regimens for advanced/metastatic melanoma generally have ORRs between 20%-58%, demonstrating IBI-363’s disruptive potential.

Finally, here is JPM’s summary timeline of clinical highlights. This nuclear bomb is on the verge of detonation.

Nuclear Bomb Explosion

Now, at the 2024 ASCO conference, this nuclear bomb has fully exploded. For NSCLC indications, data improved further compared to the 2024 WCLC meeting. We mentioned that at WCLC 2024, the 3mg/kg patients’ overall data showed 34.5% ORR, while this time the ORR reached 43.3% and confirmed ORR (cORR) 36.7%. Moreover, it showed extremely impressive efficacy in colorectal cancer. MSS/pMMR colorectal cancer is a typical cold tumor, generally not responsive to IO therapies, so IBI-363 is needed to “blow it up.”

After treatment, evaluable patient sample sizes were decent: 63 in the monotherapy group and 68 in the combination therapy group.

ORRs were 12.7% and 23.5%, respectively. Don’t underestimate these numbers; looking at subgroups, among patients without liver metastasis receiving combination therapy, ORR reached 38.7%, DCR reached 83.9%, and median PFS (mPFS) reached 9.6 months. While monotherapy is uncertain, the combination treatment in non-liver metastasis patients could potentially apply for accelerated approval. Generally, colorectal cancer patients tend to have a higher proportion without liver metastasis.

However, IBI-363 has concerns in the lung adenocarcinoma market. Among adenocarcinoma patients treated with PD-(L)1 therapy with no actionable genetic alterations, 25 patients received 3 mg/kg IBI-363 and 30 patients received 0.6/1/1.5 mg/kg IBI-363. The 3 mg/kg group showed an ORR of 28.0%, confirmed ORR 24%, which is somewhat lower than that in squamous carcinoma patients.

Whether this affects future approval in lung adenocarcinoma is a question. But minor issues won’t change the big picture: IBI-363 has already started a head-to-head Phase II clinical trial against Keytruda, targeting melanoma.