Crescent Biopharma advances CR-001 bispecific into chemo combos

Crescent Biopharma has announced a series of clinical milestones for its pipeline of oncology biologics, headlined by the opening of chemotherapy combination expansion cohorts in the global Phase 1/2 ASCEND trial of CR-001, its PD-1 x VEGF bispecific antibody. Dose escalation in ASCEND is complete, with more than 125 patients dosed across sites in the United States, Europe and South Korea.

The Waltham, Massachusetts company said it is on track to report initial monotherapy data from ASCEND in the first quarter of 2027. That readout will include a preliminary overall response rate from a first-line NSCLC cohort of up to 12 patients, alongside safety, tolerability, pharmacokinetic and pharmacodynamic data from the broader 125-plus patient population spanning multiple solid tumour types.

ASCEND expansion: seven tumour types in combination

Enrollment has now commenced in the standard of care chemotherapy combination cohorts, which span a broad range of indications: first-line NSCLC, mismatch repair proficient colorectal cancer (both first- and third-line settings), biliary tract cancer, endometrial cancer, and PD-L1-expressing gastric and gastroesophageal junction cancer in first- and second-line settings. Chemotherapy backbones include established regimens such as paclitaxel-carboplatin, mFOLFOX6, gemcitabine-cisplatin and capecitabine-oxaliplatin.

Crescent expects hundreds of patients to enrol across these cohorts, with initial combination data targeted for mid-2027. Pending those results and regulatory feedback, the company said it plans to initiate the first of multiple Phase 3 studies of CR-001 in early 2028. Chief executive Joshua Brumm said the company anticipates more than 2,000 patients dosed across the full portfolio by mid-2027, underpinned by seven IND clearances secured in collaboration with Chinese partner Kelun-Biotech.

ADC pipeline broadens the combination strategy

Beyond the ASCEND chemotherapy combinations, Crescent is positioning CR-001 as a backbone for ADC-based regimens. Multiple Phase 2 studies combining CR-001 with sacituzumab tirumotecan, Kelun-Biotech's TROP2-directed ADC, are ongoing in China in more than 700 patients, with initial data also expected mid-2027. A further combination with CR-003, an integrin-beta 6 targeted ADC, is planned for initiation in the first half of 2027.

CR-002, a topoisomerase inhibitor ADC targeting PD-L1 developed internally with Paragon Labs, received FDA IND clearance earlier this month. Crescent said it is on track to begin the global Phase 1/2 APOLLO trial this quarter in patients with advanced solid tumours including NSCLC, head and neck squamous cell carcinoma, and gastrointestinal and gynaecological cancers. Initial data from APOLLO are expected in the second half of 2027.

Market context and competitive read

The PD-1 x VEGF bispecific class has grown sharply in commercial and clinical prominence since Akeso and Summit Therapeutics reported ivonescimab data in NSCLC, generating significant investor interest in this mechanism as a potential successor to PD-1 monotherapy. Crescent's CR-001 enters a field that now includes multiple industry-sponsored programmes, meaning differentiation will depend heavily on the breadth and quality of combination data rather than monotherapy activity alone.

The ADC-plus-checkpoint combination strategy Crescent and Kelun-Biotech are pursuing mirrors moves by a number of larger oncology players, including AstraZeneca and Daiichi Sankyo, who have reported encouraging signals from TROP2 ADC combinations in NSCLC. Whether CR-001's dual PD-1 and VEGF blockade offers a meaningful advantage over standard PD-1 inhibition as a combination backbone will be the central question investors bring to the mid-2027 data readouts. Trial-in-progress posters for ASCEND are scheduled for the ESMO 2026 Congress in Madrid (23-27 October) and the SITC Annual Meeting in Phoenix (4-8 November).