A Phase 1/2, Multicenter, Open-label, Dose Escalation and Dose Expansion Study to Evaluate the Safety, Pharmacokinetics, Pharmacodynamics, and Antitumor Activity of CR-001 in Adult Participants with Locally Advanced or Metastatic Solid Tumors

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Crescent Biopharma Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Decision date (initial)

2026-06-02

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Crescent Biopharma, Inc. USA

External identifiers

EU CT number

2025-523590-42-00

ClinicalTrials.gov

NCT07335497

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Dose response, Pharmacodynamic, Pharmacokinetic, Safety

To characterize the safety and tolerability of increasing dose levels of CR-001 in successive cohorts of participants with locally advanced or metastatic solid tumors

Secondary objectives 4

1. To identify the recommended Phase 2 dose(s) (RP2D[s]) of CR-001 based on the totality of safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and clinical activity data
2. To characterize the PK profile of CR-001
3. To characterize the immunogenicity of CR-001
4. To characterize the preliminary antitumor activity of CR-001

Conditions and MedDRA coding

Locally Advanced or Metastatic Solid Tumors

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 12

1. Able to understand the study procedures and agree to participate in the study by providing a written informed consent form (ICF)
2. Age ≥ 18 years at the time of signing the ICF (or at least the age that is the regionally approved age of consent for participation in investigational clinical studies)
3. For dose escalation and backfill cohort enrollment: Is progressing from, intolerant to, or ineligible for (due to unavailability or contraindication) local standard of care (SOC) anticancer therapies (defined as those therapies that are approved by the participant’s local health authority for treatment of the disease indication and that are known to confer clinical and/or survival benefit); Participants must also have 1 of the following advanced unresectable or metastatic (incurable) solid tumor types that meets the following indication-specific criteria: a. Hepatocellular carcinoma: Has histologically or cytologically-confirmed diagnosis of HCC; fibrolamellar and sarcomatoid subtypes are not eligible. Mixed hepatocellular/ cholangiocarcinoma are eligible. Must have Barcelona Clinic Liver Cancer (BCLC) Stage C disease or BCLC Stage B disease not amenable to locoregional therapy or refractory to locoregional therapy, and not amenable to curative treatment approach. Must have a Child-Pugh Class A liver score within 7 days of first dose of study drug (Section 10.7). b. Biliary tract cancer: Has histologically-confirmed diagnosis of advanced (metastatic) and/or unresectable (locally advanced) adenocarcinoma of the biliary tract (intra-or extra-hepatic cholangiocarcinoma or gallbladder cancer) c. Endometrial carcinoma: Has histologically-confirmed diagnosis of advanced, recurrent, or metastatic endometrial carcinoma. Participants with carcinosarcoma (malignant mixed Mullerian tumor), endometrial leiomyosarcoma, endometrial stromal sarcoma, and uterine sarcoma are not eligible. d. Cervical cancer: Has histologically-confirmed diagnosis of metastatic, persistent, or recurrent squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma of the cervix not amenable for curative treatment with surgery and/or radiation therapy. Participants with small cell neuroendocrine carcinoma are not eligible. e. Ovarian cancer: Has epithelial ovarian, fallopian tube, or primary peritoneal cancer with platinum-resistant disease defined as a platinum-free interval of < 6 months. Participants with platinum-sensitive disease defined as a platinum-free interval of ≥ 6 months and with at least 2 prior lines of platinum-containing therapy are also eligible. Participants with primary platinum-refractory disease defined as disease that did not respond or has progressed within 3 months of the last dose of platinum-containing therapy in the first line are not eligible. Participants with nonepithelial tumors, including malignant mixed Mullerian tumors or low-grade or borderline ovarian tumors, are not eligible. f. Gastric and GEJ cancer: Has histologically or cytologically-confirmed diagnosis of metastatic gastric adenocarcinoma and tumor PD-L1 expression Combined Positive Score (CPS) ≥ 1. Participants with squamous cell or undifferentiated gastric cancer are not eligible. g. Colorectal cancer: Has histologically or cytologically-confirmed metastatic colon or rectal adenocarcinoma h. Non-small-cell lung cancer: Has histologically or cytologically-confirmed advanced or metastatic NSCLC and tumor PD-L1 expression Tumor Proportion Score (TPS) ≥ 1%. Participants with known epidermal growth factor receptor (EGFR)-sensitizing mutations or anaplastic lymphoma kinase (ALK) translocations are allowed if they have received or progressed on an approved tyrosine kinase inhibitor; participants with non-squamous NSCLC are required to have tissue-based test reports demonstrating EGFR and ALK status; testing is not required for participants with squamous NSCLC if EGFR or ALK status is unknown
4. For backfill and dose optimization cohort participants only: Must have availability and willingness to provide archival tumor tissue from the most recent biopsy, preferably within 3 years of the date of consent; alternatively, must have a tumor lesion amenable to a low-risk, medically-routine biopsy and must have willingness to undergo biopsy. In dose escalation cohort participants, the availability of tumor tissue (archival or fresh) is not required but is preferred (Section 8.8.1).
5. Must have at least 1 measurable target lesion as defined by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria (Section 10.5.4). A measurable lesion situated in a previously irradiated area may qualify as a target lesion if progression has been demonstrated in such lesion post-irradiation. Radiation involving measurable lesions must not be anticipated during study participation.
6. Has a life expectancy of ≥ 3 months
7. Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
8. Has laboratory values meeting the following criteria: a. Aspartate aminotransferase (AST), alanine aminotransferase (ALT) ≤ 2.5 × upper limit of normal (ULN), or ≤ 5 × ULN for participants with liver metastases b. Total bilirubin ≤ 1.5 × ULN; (≤ 3 × ULN in participants with known Gilbert disease) c. Albumin ≥ 2.8 g/dL d. International normalized ratio (INR) ≤ 1.5 × ULN, unless the participant is receiving anticoagulant therapy and prothrombin time (PT) or partial thromboplastin time (PTT) is within therapeutic range of intended use of the appropriate anticoagulants e. Glomerular filtration rate (GFR) ≥ 50 mL/min based on the Chronic Kidney Disease Epidemiology Collaboration creatinine GFR estimation (Inker et al., 2021) f. Urine protein < 2+ on dipstick or 24-hour urine protein quantification < 1.0 g g. Total cholesterol ≤ 300 mg/dL; triglycerides ≤ 2.5 × ULN h. Has adequate hematologic reserve, as defined below, without transfusion or use of growth factors for at least 7 days: 1. Absolute neutrophil count (ANC) ≥ 1.5 × 109/L 2. Platelets ≥ 100 × 109/L 3. Hemoglobin ≥ 9 g/dL
9. Is willing and able to comply with scheduled study visits, follow-up visits, treatment plans, and other considerations required during the study
10. Satisfies the following timing requirements with respect to prior therapy and surgery: a. Prior systemic anticancer therapy (including investigational drugs): at least 3 weeks or at least 5 half-lives, whichever is shorter, between administration of the last dose and administration of first dose of study drug b. Radiotherapy: at least 28 days must have elapsed since the last radiotherapy; palliative radiation therapy during screening is permitted so long as it does not involve target lesion(s) c. Surgery: at least 14 days must have elapsed prior to the first dose of study drug, and the participant must have recovered from any clinically relevant effects from any prior surgery
11. Agrees to not donate ova or sperm, or breastfeed (if applicable) from the first dose of study drug until 120 days after the last dose of study drug
12. Agrees with the following contraceptive requirements: a. Fertile female participants (defined in Section 10.4.1) must have a negative serum pregnancy test at screening and a negative urine pregnancy test within 72 hours prior to the first dose of study drug. Fertile female participants must agree to use at least 1 highly effective method of contraception (Section 10.4.2.1) from the start of screening until 120 days after the last dose of study drug.b. If non-vasectomized male participant has heterosexual intercourse with a fertile female partner, the participant must use a male condom and have the female partner agree to use at least 1 highly effective method of contraception (Section 10.4.2.1) from the start of screening until Day 120 after the last dose of study drug.

Exclusion criteria 20

1. Has malignancies other than disease under study within 3 years prior to Cycle 1 Day 1, with the exception of those with a negligible risk of metastasis or death and with expected curative outcome (such as adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, localized prostate cancer treated surgically with curative intent, or ductal carcinoma in situ treated surgically with curative intent) or undergoing active surveillance per standard-of-care management
2. Has conditions requiring treatment with clinically significant or increasing doses of systemic steroid therapy (> 10 mg per day of prednisone or equivalent) or any other systemic immunosuppressive medication within 7 days of first dose of study drug. The use of a stable dose of systemic steroids and/or immunosuppressive medication used for hormone replacement is permitted with Sponsor approval. Local or targeted steroid and immunosuppressive therapies (eg, inhaled or topical steroids) are acceptable
3. Has not adequately recovered from recent major surgery (excluding placement of vascular access), in the opinion of the Investigator
4. Has ongoing clinically significant toxicity related to prior therapy (including radiotherapy or surgery). Any ongoing toxicity must have returned to Grade ≤ 1 or baseline by 14 days before the start of study drug or be deemed irreversible and stable by the Investigator. NOTE: Exceptions include alopecia, neuropathy, appropriately controlled endocrine toxicities, and other well-controlled/stable toxicities may be included after consultation with the Sponsor Medical Monitor
5. Has a known sensitivity to any component of CR-001
6. For backfill and dose optimization cohort participants only: Has received prior PD-(L)1/VEGF bispecific antibody or investigational immune checkpoint inhibitors (eg, anti-PD-1/L1, anti-CTLA-4, PD-(L)1/VEGF, anti-TIGIT, anti-LAG3) that are not considered as SOC therapy for the disease under study. Receipt of other prior non-immune checkpoint inhibitor investigational immunotherapy is acceptable
7. Has uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (ie, once monthly or more frequently). Participants with an indwelling pleural catheter or percutaneous pigtail catheter for stable drainage will be eligible if assessed to be well controlled per the Investigator.
8. Has active central nervous system (CNS) metastases. Participants with previously treated brain metastases (eg, surgery or radiotherapy) who are clinically stable for at least 2 weeks (including from the start of study drug) and who have discontinued corticosteroids for 7 days prior to the first dose of study drug are allowed to participate. Participants with untreated and asymptomatic brain metastases (ie, no neurological symptoms, no need for corticosteroids, no brain metastases with a long axis > 1.5 cm, and no significant peritumoral edema) are eligible for inclusion. Participants with leptomeningeal disease are not eligible for the study
9. Has active autoimmune disease requiring systemic therapy (eg, disease-modifying drugs, corticosteroids, or immunosuppressive medications) in the past 2 years; replacement therapy (eg, thyroid hormone, insulin, or physiological corticosteroid replacement therapy for adrenal or pituitary insufficiency) is permitted
10. Has a history of serious Grade ≥ 3 immune-related adverse event (irAE) that led to treatment discontinuation of a prior immunotherapy. Participants with a history of Grade 3 or higher irAEs that did not lead to treatment discontinuation of a prior immunotherapy should be discussed with the Sponsor Medical Monitor.
11. Has a history of noninfectious pneumonitis/interstitial lung disease requiring systemic glucocorticoid therapy or has noninfectious pneumonitis at screening. History of radiation pneumonitis in the radiation field (fibrosis) is permitted.
12. Has an active severe infection. Participant is permitted to enroll once any required antibiotic and/or antifungal therapy has been completed and the infection is determined to be controlled at least 2 weeks prior to first dose of study drug
13. Has received a live or attenuated vaccine within 30 days of the first dose
14. Has undergone prior allogeneic stem cell or solid organ transplantation
15. Has an active Hepatitis B infection (hepatitis B surface antigen [HBsAg] reactive) or Hepatitis C infection with detectable viral load (HCV RNA). Participants with past hepatitis B virus (HBV) infection or resolved HBV infection (defined as the presence of hepatitis B core antibody and absence of HBsAg) may be enrolled provided they received HBV antiviral therapy for at least 4 weeks and HBV DNA is negative
16. If there is a known history of detectable human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS), has experienced AIDs-related illness within the past 6 months or has a detectable HIV viral load (HIV RNA), or has CD4+ T cell count < 350 cells/mm3
17. Has any medical or psychological condition that, in the opinion of the Investigator: a. Prevents or interferes with the participant’s ability to participate in the study; b. Places the participant at unacceptable risk if the participant was to participate in the study; or c. Confounds the ability to interpret data from the study
18. Imaging at screening shows that the tumor surrounds important blood vessels or has obvious necrosis or cavities, and the Investigator determines that participation in the study would cause a risk of bleeding during the study period
19. Events related to gastrointestinal perforation, surgery, wound healing complications, and bleeding described below:a. History of abdominal or tracheoesophageal fistula, gastrointestinal perforation, abdominal fistula, or intra-abdominal abscess within 6 months prior to the first dose of study drug b. Presence of gastrointestinal obstruction or requirement for routine parenteral hydration, parenteral nutrition, or tube feeding c. Presence of severe nonhealing wounds, active ulcers, or untreated bone fractures d. Presence of intra-abdominal free air not explained by paracentesis or recent surgery e. History of hemoptysis (≥ 1 teaspoon of bright red blood or small clots per episode; participants with blood-tinged sputum are included) or acute gastrointestinal bleeding within 6 months prior to the first dose of study drug (note: transient hemoptysis associated with diagnostic bronchoscopy is allowed) f. History of bleeding diathesis or coagulation disorders (in the absence of therapeutic anticoagulation)
20. 20. Has clinically significant cardiovascular disease: a. Poorly controlled hypertension (defined as systolic blood pressure > 150 mmHg and/or diastolic blood pressure > 100 mmHg). Note: Antihypertensive therapy to achieve these parameters is allowable. b. History of hypertensive crisis or hypertensive encephalopathy c. History of myocarditis or cardiomyopathy d. History of Major vascular disease (eg, aortic aneurysm requiring surgery, any arterial thrombosis, or NCI CTCAE v6.0 Grade 3 or higher venous thromboembolism):Grade 2 venous thromboembolism within 12 months prior to the first dose of study drug is also excluded unless participants are appropriately managed on stable dose of anticoagulants. e. Myocardial infarction or unstable angina within 6 months prior to the first dose of study drug f. New York Heart Association Class II or higher congestive heart failure (Section 10.6), mean resting corrected QT interval (QTc) > 480 msec by Fridericia QT correction, or any factors that increase the risk of QTc prolongation such as congenital long QT syndrome, or family history of long QT syndrome g. Severe cardiac arrhythmia requiring medication (asymptomatic atrial fibrillation with controlled ventricular rate can be included) h. History of cerebrovascular disease within 12 months prior to the first dose of study drug i. Left ventricular ejection fraction (LVEF) < 50%

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. Incidence and nature of dose-limiting toxicities (DLTs) during Cycle 1 (28 days) of CR-001 administration, and maximum tolerated dose (MTD) characterization, if applicable
2. Incidence, nature, and severity of treatment-emergent adverse events (TEAEs) and treatment-emergent serious adverse events (SAEs), graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE)
3. Severity and nature of TEAEs leading to dose modifications and treatment discontinuation

Secondary endpoints 4

1. Determination of RP2D(s): The RP2D will be determined based on a review of available safety, tolerability, PK, PD, and clinical activity data
2. Serum PK parameters: area under the curve from time 0 extrapolated to infinity (AUC0--inf), area under the concentration-time curve from time 0 to the time of the last quantifiable concentration (AUClast), maximum concentration (Cmax), time to maximum concentration (Tmax), volume of distribution (Vd), clearance (CL), and elimination half-life (t½) after a single dose and steady state PK parameters as appropriate
3. Incidence of participants with detectable antidrug antibodies (ADAs)
4. Overall response rate (ORR), duration of response (DOR), disease control rate (DCR), time to response (TTR) progression-free survival (PFS), overall survival (OS), and best percent change in target lesions

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Crescent Biopharma Inc.

Sponsor organisation

Crescent Biopharma Inc.

Address

300 5th Avenue Ste 1010

City

Waltham

Postcode

02451-8778

Country

United States

Scientific contact point

Organisation

Crescent Biopharma Inc.

Contact name

Bradley Sumrow MD

Public contact point

Organisation

Crescent Biopharma Inc.

Contact name

Bradley Sumrow MD

Third parties 6

Locations

1 EU/EEA country · 5 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 20 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications