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Last updated: June 20, 2026
A bispecific checkpoint inhibitor is a single antibody engineered to bind TWO immune checkpoint targets on T cells (or in the tumor microenvironment) at the same time. The two-target design is intended to deliver multi-checkpoint blockade with a single molecule and potentially a better therapeutic index than combining two separate antibodies. Five target pairings dominate current clinical development:
Bispecific checkpoint inhibitors are distinct from bispecific T-cell engagers (TCEs) like blinatumomab (CD19 × CD3, leukemia), tarlatamab (DLL3 × CD3, SCLC), or tebentafusp (gp100 × CD3, uveal melanoma) — TCEs physically link a tumor antigen to CD3 on T cells, recruiting any T cell to kill the tumor. Checkpoint bispecifics instead block the inhibitory signals that normally restrain T-cell activity.
Tebentafusp (Kimmtrak) is included on this hub as a related class because it is the only FDA-approved bispecific molecule used in oncology that doesn't combine two checkpoints, and patients with uveal melanoma searching for bispecific options will look for it here.
| Drug | Sponsor | Target | Regulatory Status | Lead Indications |
|---|---|---|---|---|
| Cadonilimab (AK104, Vyvgart) | Akeso (China) | PD-1 × CTLA-4 | NMPA approved (China): 2L+ recurrent or metastatic cervical cancer; 1L locally advanced unresectable or metastatic gastric/GEJ adenocarcinoma + chemotherapy. Not FDA-approved. | Cervical, Gastric/GEJ, HCC (adjuvant Ph3 NCT05489289), NPC, NSCLC, CRC, Pancreatic, Cholangio |
| Ivonescimab (AK112) | Akeso / Summit Therapeutics | PD-1 × VEGF | NMPA approved (China): 1L EGFR-mutant locally advanced or metastatic NSCLC + chemotherapy (HARMONi-2). FDA PDUFA Nov 14, 2026 for HER2-negative gastric/GEJ adenocarcinoma. | NSCLC (home court, HARMONi-7 + HARMONi-6 + HARMONi-2), HNSCC, Gastric, TNBC, CRC, SCLC consolidation |
| Rilvegostomig (AZD2936) | AstraZeneca | PD-1 × TIGIT | Investigational. Cross-mechanism Ph3 program. AstraZeneca pembrolizumab successor across ADCs. | Biliary tract (T-DXd combo NCT06467357), Endometrial (T-DXd, DESTINY-Endometrial01), Gastric (T-DXd), NSCLC (Dato-DXd 1L), CLDN18.2 advanced (sonesitatug vedotin), HCC (bevacizumab, ARTEMIDE-HCC01) |
| QL1706 (Iparomlimab + Tuvonralimab) | Qilu Pharma | PD-1 × CTLA-4 | Investigational. Largest single-program pipeline footprint (158 trials). | NSCLC (1L + neoadjuvant), Cervical, Gastric, HCC, Liver, Bladder, Esophageal, MSI-H CRC, CLDN18.2 combos (sibling-hub) |
| Volrustomig (MEDI5752) | AstraZeneca | PD-1 × CTLA-4 | Investigational. Phase 3 in cervical (high-risk LACC NCT06079671) and HNSCC (locally advanced NCT06129864). | Cervical (Ph3), HNSCC (Ph3), Ph2 expansion |
| Erfonrilimab (KN046) | Alphamab | PD-L1 × CTLA-4 | Investigational. | NSCLC, Pancreatic, Solid tumor basket |
| HX008 | Hengrui Pharma | PD-1 × CTLA-4 | Investigational. | Solid tumor expansion |
| MGD019 / Lorigerlimab | MacroGenics | PD-1 × CTLA-4 | Investigational. | Solid tumor, mCRPC |
| SHR-1701 | Hengrui Pharma | PD-L1 × TGF-β trap | Investigational. | Solid tumor combinations |
| Bintrafusp Alfa (M7824) | Merck KGaA / GSK | PD-L1 × TGF-β trap | Development discontinued 2021 after NSCLC Phase 3 failure. Few residual trials remain. | Residual academic trials only |
| Tebentafusp (Kimmtrak) — related class, included for searchability | Immunocore | gp100 × CD3 (TCR-bispecific T-cell engager — different mechanism) | FDA Jan 2022 + EMA approved: HLA-A*02:01-positive adult uveal melanoma. First systemic therapy with OS benefit in this rare cancer. | Uveal melanoma (metastatic + adjuvant Ph3) |
Akeso's PD-1/CTLA-4 bispecific antibody. NMPA-approved (China) for 2L+ recurrent or metastatic cervical cancer (based on COMPASSION-13) and for 1L locally advanced unresectable or metastatic gastric/GEJ adenocarcinoma in combination with chemotherapy (COMPASSION-15). Cadonilimab's key Phase 3 program includes NCT05489289 (adjuvant cadonilimab in HCC with high recurrence risk, post-resection — ASCO 2026 wrap-up takeaway), NCT05941741 (LANPC induction chemo + low-dose RT + cadonilimab), NCT06241599 (Ph2/3 in HCC), NCT06832917 (rectal cancer short-course RT + cadonilimab + mFOLFOX6), NCT06542549 (broad chemo combination), NCT07449780 (SC formulation + XELOX), NCT05990127 (cadonilimab vs tislelizumab + chemo as 1L PD-L1+ NSCLC). 111 ClinTrialFinder corpus trials — the second-largest single-drug footprint after QL1706. Cross-mechanism combinations: NCT06221748 disitamab vedotin + cadonilimab in HER2-expressing gastric (HER2 ADC hub overlap); NCT06492317 RC48 + cadonilimab in HER2-overexpressing gastric (CLDN18.2 hub overlap via LM-302 + cadonilimab combos NCT06519591 + NCT06587425). See the cadonilimab drug page for full per-indication detail.
Akeso/Summit Therapeutics's PD-1/VEGF bispecific antibody. NMPA-approved (China) for 1L EGFR-mutant locally advanced or metastatic NSCLC + chemotherapy based on HARMONi-2. FDA PDUFA action date November 14, 2026 for HER2-negative gastric/GEJ adenocarcinoma. Key Phase 3 program: NCT05899608 (HARMONi-2 1L EGFR-mut NSCLC); NCT06601335 (Ph3 R/M HNSCC vs pembrolizumab + AK117); NCT06767514 (HARMONi-7 1L NSCLC vs pembrolizumab); NCT06767527 (Ph3 1L TNBC + nab-paclitaxel); NCT06928389 (Ph3 + docetaxel in advanced NSCLC); NCT06951503 (Ph3 1L mCRC + chemo, HARMONi-GI3); NCT06953999 (Ph3 metastatic pancreatic + chemo + AK117); NCT07010263 (LS-SCLC consolidation). 124 ClinTrialFinder corpus trials. See the ivonescimab drug page for full per-indication detail and NCT06419621 disambig.
AstraZeneca's PD-1/TIGIT bispecific. The most strategically distinct bispecific checkpoint inhibitor in current development because of its uniquely broad combination Phase 3 program with AstraZeneca's growing ADC pipeline. Phase 3 trials: NCT06467357 (T-DXd + rilvegostomig vs SoC in HER2-expressing biliary tract); NCT06989112 (DESTINY-Endometrial01: T-DXd + rilvegostomig or pembrolizumab in HER2-expressing endometrial); NCT06764875 (rilvegostomig + fluoropyrimidine + T-DXd in 1L HER2+ gastric); NCT07431281 (sonesitatug vedotin + capecitabine + rilvegostomig in CLDN18.2+ disease); NCT06357533 (Dato-DXd + rilvegostomig in 1L NSCLC); NCT06921785 (rilvegostomig + bevacizumab ± chemo in HCC, ARTEMIDE-HCC01); NCT06627647 + NCT06692738 + NCT06868277 (multiple monotherapy or chemo head-to-head vs pembrolizumab in 1L NSCLC). 17 ClinTrialFinder corpus trials. Rilvegostomig is positioned as AstraZeneca's pembrolizumab successor — the cross-mechanism cluster pattern means a single positive Phase 3 readout for the bispecific class could lift the broader AstraZeneca ADC + bispecific pipeline.
Qilu Pharma's PD-1/CTLA-4 dual-antibody program. The largest single-drug footprint in the bispecific checkpoint inhibitor space — 158 ClinTrialFinder corpus trials covering NSCLC (1L + adjuvant + neoadjuvant + SCLC), cervical, gastric, HCC, biliary, MSI-H CRC, bladder, esophageal, breast, and pan-tumor. Phase 3 trials include NCT05487391 (adjuvant NSCLC + platinum chemo), NCT06686576 (neoadjuvant dMMR/MSI-H resectable CRC), NCT05976568 (1L combination + bevacizumab/chemo), NCT06789796 (QL1706 or QL1604 in LS-SCLC), NCT07025239 (vs placebo + bev + XELOX), NCT07613567 (neoadjuvant chemo), NCT07636226 (anlotinib later-line lung), NCT06910072 (paclitaxel polymeric micelles + carboplatin + iparomilimab + tuvonralimab). The QL1706 development pattern combines aggressive trial design (rapid Ph2 → Ph3) with broad combination footprints — even with 96 NYR trials, the program is moving fast.
AstraZeneca's PD-1/CTLA-4 bispecific. Two registrational Phase 3 trials: NCT06079671 (volrustomig in high-risk locally advanced cervical cancer) and NCT06129864 (volrustomig in unresected locally advanced HNSCC). The volrustomig Phase 3 program targets earlier-disease curative-intent settings (locally advanced disease, not metastatic), positioning the bispecific as a curative-intent adjunct alongside chemoradiation — a different strategic angle than rilvegostomig's metastatic-disease combination program. 9 ClinTrialFinder corpus trials.
Alphamab's PD-L1/CTLA-4 bispecific (anti-PD-L1 paired with anti-CTLA-4). Phase 2 programs across NSCLC, pancreatic, and pan-tumor basket. 4 ClinTrialFinder corpus trials. The PD-L1/CTLA-4 geometry is different from cadonilimab + QL1706 + volrustomig (PD-1/CTLA-4) — whether PD-L1-anchoring vs PD-1-anchoring matters clinically remains an open question.
MacroGenics's PD-1/CTLA-4 bispecific. 2 ClinTrialFinder corpus trials including a Ph2 in metastatic castration-resistant prostate cancer (mCRPC) — the only bispecific checkpoint inhibitor with a dedicated prostate cancer program. Patients with mCRPC searching for IO options should review this trial alongside the PSMA radioligand therapy hub.
Hengrui's anti-PD-L1 antibody fused to the TGF-β-receptor-II extracellular domain — a bifunctional molecule that combines checkpoint blockade with TGF-β neutralization. The TGF-β trap component aims to address the tumor microenvironment immunosuppression that has been hypothesized to limit single-agent anti-PD-1 efficacy in some settings. 14 ClinTrialFinder corpus trials — the second-largest TGF-β trap program after bintrafusp alfa (which was discontinued).
Hengrui's PD-1/CTLA-4 bispecific. 4 ClinTrialFinder corpus trials, primarily in solid tumor expansion combinations.
Merck KGaA's anti-PD-L1 × TGF-β trap. Bintrafusp alfa was the lead program in this bifunctional class but development was discontinued in 2021 after the bintrafusp Phase 3 in NSCLC failed to meet its primary endpoint. We surface bintrafusp alfa here only because residual academic trials remain open in the ClinTrialFinder corpus — we do not promise patients access to bintrafusp alfa as an approved therapy or a Phase 3 candidate. Patients interested in the PD-L1/TGF-β trap class should focus on SHR-1701 or related investigational agents.
The first FDA-approved bispecific molecule in solid-tumor oncology (January 2022). Tebentafusp is a TCR-CD3 bispecific (engineered TCR targeting the gp100 melanoma-associated peptide presented by HLA-A*02:01, fused to anti-CD3) — mechanistically distinct from the dual-checkpoint bispecifics above. FDA-approved for HLA-A*02:01-positive adult patients with unresectable or metastatic uveal melanoma. 11 ClinTrialFinder corpus trials: Phase 3 NCT05549297 (tebentafusp regimen vs investigator's choice in previously-treated advanced uveal melanoma); NCT06246149 (adjuvant tebentafusp in high-risk ocular melanoma); plus Phase 1/2 combination expansion. HLA-A*02:01 testing required upfront. We include tebentafusp on this hub as a related-class option because patients searching for systemic uveal melanoma therapy will look for it here.
The 243 recruiting (and 202 not-yet-recruiting) bispecific checkpoint inhibitor trials are grouped by primary cancer type below. The most clinically pressing eligibility question is usually prior pembrolizumab or nivolumab exposure — many Phase 3 trials are head-to-head with pembrolizumab in IO-naive patients.
NSCLC is the largest single-cancer cluster in this hub. Ivonescimab is NMPA-approved here (1L EGFR-mut); rilvegostomig has three head-to-head Phase 3 trials vs pembrolizumab; QL1706 has multiple adjuvant + neoadjuvant programs.
The largest disease cluster (44 trials). Cadonilimab is NMPA-approved 1L gastric/GEJ + chemo. Ivonescimab has FDA PDUFA Nov 14, 2026 for HER2-negative gastric/GEJ. Rilvegostomig + T-DXd is in HER2+ gastric Phase 3.
Cadonilimab is NMPA-approved 2L+ cervical; volrustomig has Phase 3 in high-risk locally advanced cervical curative-intent setting.
Three Phase 3 programs: cadonilimab in adjuvant (post-resection high-recurrence-risk), rilvegostomig + bevacizumab in 1L advanced (ARTEMIDE-HCC01), and QL1706 + bevacizumab/chemo in 1L.
FDA-approved Jan 2022 for HLA-A*02:01-positive metastatic uveal melanoma. Two Phase 3 expansion trials open.
Showing 243 RECRUITING + 202 not-yet-recruiting bispecific checkpoint inhibitor interventional trials in the ClinTrialFinder corpus as of June 20, 2026 (50 Phase 3 across the class). Trials enrolling only into completed cohorts and bispecific T-cell engagers without checkpoint co-targets (blinatumomab, tarlatamab, teclistamab, etc.) are out of scope; see BCMA Bispecifics and GPRC5D Bispecifics for those classes. For the latest searches: cadonilimab, ivonescimab, rilvegostomig, QL1706.
The single most strategically distinctive bispecific checkpoint inhibitor program is AstraZeneca's rilvegostomig (AZD2936) — not for the drug's own monotherapy efficacy (which is being tested) but for the cross-mechanism Phase 3 cluster in which rilvegostomig replaces pembrolizumab as the PD-1 backbone of AstraZeneca's ADC combinations. The combinations span three other ClinTrialFinder hubs:
This cross-mechanism cluster means a single positive Phase 3 readout for rilvegostomig in 1L NSCLC could lift the entire AstraZeneca ADC + bispecific pipeline simultaneously. Watch this cluster closely — it is the most consequential single-drug bet in the bispecific checkpoint inhibitor space.
Ipilimumab + nivolumab (Yervoy + Opdivo) is the established separate-drug PD-1 + CTLA-4 combination. The combination has demonstrated overall survival benefit in melanoma (CheckMate-067), 1L mCRC MSI-H, 1L HCC, 1L NSCLC PD-L1+, RCC, and others — but carries a high rate of grade 3+ immune-related adverse events (irAEs).
| Class | FDA Approvals | Distinctive Trade-Offs |
|---|---|---|
| Bispecific PD-1 × CTLA-4 (this hub) | Cadonilimab: NMPA cervical + 1L gastric/GEJ. Others: investigational. | Single molecule with dual-affinity geometry; lower grade 3+ irAE rates than reported ipi+nivo benchmarks in cadonilimab cervical/gastric trials; single-IV administration; potentially TME-biased binding |
| Separate-Drug Ipilimumab + Nivolumab | Multiple: melanoma, RCC, MSI-H CRC, 1L HCC, 1L NSCLC PD-L1+, mesothelioma, esophageal | Well-validated efficacy across many cancers; high grade 3+ irAE rate (~30-40% in melanoma); separate scheduling (e.g., ipi q3w × 4 + nivo continuation); proven OS benefit data |
| PD-1 Monotherapy (Pembrolizumab, Nivolumab) | Multiple FDA approvals across 25+ cancers | Best safety profile; modest single-agent activity in PD-L1+ tumors; the standard backbone that bispecifics are being tested against |
How bispecific checkpoint inhibitors are positioned in practice. Cadonilimab in its NMPA-approved cervical and gastric settings has demonstrated lower grade 3+ irAE rates than reported ipi+nivo benchmarks in those settings — supporting the hypothesis that the dual-affinity geometry of bispecific antibodies may bias binding toward tumor-microenvironment T cells expressing both checkpoints, rather than peripheral T cells. Head-to-head bispecific-vs-separate-combo Phase 3 trials are starting to read out; cross-trial efficacy/safety comparisons absent randomized data are not reliable. The single most clinically pressing eligibility question for any bispecific Phase 3 trial is usually prior pembrolizumab or nivolumab exposure — many trials are IO-naive only.
Bispecific checkpoint inhibitors share the immune-related adverse event (irAE) signal of single-checkpoint anti-PD-1 / anti-PD-L1 / anti-CTLA-4 therapies, but with potentially different magnitude:
What is a bispecific checkpoint inhibitor?
A bispecific checkpoint inhibitor is a single antibody engineered to simultaneously bind TWO immune checkpoint targets — PD-1 paired with CTLA-4 (cadonilimab, QL1706, volrustomig, MGD019, HX008), PD-1 with VEGF (ivonescimab), PD-1 with TIGIT (rilvegostomig), PD-L1 with CTLA-4 (erfonrilimab), or PD-L1 with TGF-β trap (SHR-1701, bintrafusp). The two-target design delivers multi-checkpoint blockade with a single molecule, potentially with better therapeutic index than combining two separate antibodies. Bispecific checkpoint inhibitors are distinct from bispecific T-cell engagers (TCEs) like blinatumomab, tarlatamab, or tebentafusp — those physically link a tumor antigen to CD3 on T cells.
Is cadonilimab (AK104) or ivonescimab (AK112) approved for my cancer?
Cadonilimab (AK104, Akeso) is NMPA-approved (China) for: (1) recurrent or metastatic cervical cancer 2L+; (2) 1L locally advanced unresectable or metastatic gastric/GEJ adenocarcinoma + chemotherapy. NOT FDA-approved. Ivonescimab (AK112) is NMPA-approved (China) for 1L EGFR-mutant locally advanced or metastatic NSCLC + chemotherapy. NOT FDA-approved but has FDA PDUFA Nov 14, 2026 for HER2-negative gastric/GEJ adenocarcinoma. The other bispecific checkpoint inhibitors (rilvegostomig, QL1706, volrustomig, erfonrilimab, HX008, MGD019, SHR-1701) are all investigational. Consult current FDA prescribing information for the most up-to-date label.
How are bispecific checkpoint inhibitors different from ipilimumab + nivolumab?
Ipilimumab + nivolumab is the established separate-drug PD-1 + CTLA-4 combination. The clinical rationale for PD-1/CTLA-4 bispecific antibodies (cadonilimab, QL1706, volrustomig, MGD019, HX008) is that a single bispecific molecule may deliver dual-checkpoint blockade with a potentially better safety profile than ipi+nivo — possibly because the dual-affinity geometry biases binding toward tumor-microenvironment T cells. Cadonilimab's NMPA-approved cervical and gastric labels showed lower grade 3+ irAE rates than reported ipi+nivo benchmarks. Head-to-head Phase 3 trials are starting to read out.
What is rilvegostomig (AZD2936) and why does it appear in so many other-class Phase 3 trials?
Rilvegostomig (AZD2936) is AstraZeneca's PD-1/TIGIT bispecific. It is positioned as AstraZeneca's pembrolizumab successor in combination with the company's growing ADC pipeline. Rilvegostomig Phase 3 combinations span three other ClinTrialFinder hubs: T-DXd in biliary (NCT06467357), gastric (NCT06764875), endometrial (DESTINY-Endometrial01 NCT06989112) — HER2 ADC hub; sonesitatug vedotin + capecitabine (NCT07431281) — CLDN18.2 hub; Dato-DXd + rilvegostomig 1L NSCLC (NCT06357533). Plus head-to-head vs pembrolizumab in 1L NSCLC (NCT06627647 + NCT06692738 + NCT06868277). This cross-mechanism cluster means a positive readout could lift the entire AstraZeneca ADC + bispecific pipeline.
Is tebentafusp (Kimmtrak) a bispecific checkpoint inhibitor?
Tebentafusp (Kimmtrak, Immunocore) is FDA-approved (January 2022) for HLA-A*02:01-positive adult patients with unresectable or metastatic uveal melanoma. Tebentafusp is a bispecific molecule but mechanistically different from the dual-checkpoint bispecifics: it's a TCR-CD3 bispecific (engineered TCR targeting the gp100 peptide presented by HLA-A*02:01, fused to anti-CD3). The TCR end binds the tumor antigen; the CD3 end recruits patient T cells. Tebentafusp is included on this hub as a related-class option because patients with uveal melanoma searching for systemic therapy will look for it here. HLA-A*02:01 testing required upfront.
How do I find a bispecific checkpoint inhibitor trial that fits my situation?
Use ClinTrialFinder's AI-powered matching to surface bispecific checkpoint inhibitor trials based on your specific situation — primary cancer type, biomarker status (PD-L1 CPS, HER2 IHC, EGFR mutation, MSI-H, HLA-A*02:01 for tebentafusp), prior IO exposure (treatment-naive vs prior pembrolizumab/nivolumab), prior systemic therapy, line of therapy, performance status, and country. The most clinically pressing question is usually 'have I had prior pembrolizumab or nivolumab' — many bispecific Phase 3 trials are head-to-head with pembrolizumab in IO-naive patients. For drug-page detail see /drugs/cadonilimab and /drugs/ivonescimab. For sibling hubs see HER2 ADCs (rilvegostomig + T-DXd) and CLDN18.2 (rilvegostomig + sonesitatug vedotin).
Find Matching Bispecific Checkpoint Inhibitor Trials
Use ClinTrialFinder's AI-powered matching to find cadonilimab, ivonescimab, rilvegostomig, QL1706, volrustomig, tebentafusp, and other bispecific checkpoint inhibitor trials based on your cancer type, biomarker status, prior IO exposure, and country.
Find Matching Bispecific Checkpoint Inhibitor TrialsThis page is for information only and is not medical advice. ClinTrialFinder helps you find clinical trials that may match your situation, but enrollment decisions and treatment choices should always be made with your medical oncologist. Trial eligibility, recruitment status, and treatment details can change — verify directly with the trial sponsor or on ClinicalTrials.gov before acting on any information here. FDA / NMPA approval dates and indications are summarized for context only; consult the current FDA prescribing information for each drug for authoritative regulatory status.