CR-001 in Adult Participants With Locally Advanced or Metastatic Solid Tumors (ASCEND)

Crescent Biopharma, Inc.

Status and phase: Enrolling; Phase 2; Phase 1

Conditions: Locally Advanced / Metastatic Solid Tumors

Treatments: Drug: FOLFOX; Drug: Paclitaxel; Drug: trifluridine and tipiracil; Drug: Cisplatin; Drug: Oxaliplatin; Drug: Pemetrexed; Drug: CR-001; Drug: Gemcitabin; Drug: Carboplatin; Drug: Capecitabine

Study type: Interventional

Funder types: Industry

Identifiers

NCT07335497

2025-523590-42-00 (EU Trial (CTIS) Number)

CR-001-101

2025

Details and patient eligibility

About

The purpose of this study is to determine the safety and tolerability of monotherapy CR-001 and identify the maximum tolerated dose (MTD), and/or optimal biologic dose and Recommended Phase 2 Dose(s) (RP2D) in participants with locally advanced or metastatic solid tumors.

Full description

The study will be 4 parts: dose escalation, backfill, dose expansion and dose optimization cohorts. The study will follow a stepwise approach, beginning with a typical dose escalation in participants with selected indications of advanced solid tumors. Additional participants will enroll in the backfill part at select dose levels that have been previously cleared for safety by the safety review committee. Dose expansion will enroll 7 cohorts of participants who will receive CR-001 in combination with chemotherapy. In dose optimization, participants will be randomized to one of two CR-001 dose levels.

All participants will undergo a screening period, a treatment period of up to 2 years, a safety follow-up period, and long-term efficacy and survival follow-up. During the treatment period, participants will undergo clinical and safety assessments including disease assessment scans and blood laboratory safety, pharmacokinetic, and pharmacodynamic assessments. After treatment ends, disease scans will continue until disease progression, and long-term follow-up visits will be conducted by telephone every 3 months.

Enrollment: 540 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion Criteria

• Life expectancy ≥ 3 months

• Eastern Cooperative Oncology Group (ECOG) performance status score of 0 - 1

• Adequate organ function and hematologic reserve based on laboratory parameters

• Have measurable disease defined by RECIST v1.1

• For Backfill, Dose Expansion and Dose Optimization: Willingness to provide recent archival tumor tissue sample or willingness to undergo biopsy

• Tumor Indication specific inclusion criteria:

• For dose escalation or backfill: progressing from, intolerant to, or ineligible for (due to unavailability or contraindication) local standard of care therapies and have one of the following locally advanced or metastatic tumor types:

  • Non-small cell lung cancer (NSCLC)
  • Hepatocellular carcinoma (HCC)
  • Biliary tract cancer (BTC)
  • Endometrial carcinoma
  • Cervical cancer
  • Ovarian cancer
  • Gastric or gastroesophageal cancer (GC/GEJ)
  • Colorectal cancer (CRC)

• For dose expansion: have one of the following locally advanced or metastatic tumor types:

  • 1L Non-small cell lung cancer (NSCLC)
  • 1L Colorectal cancer (CRC)
  • 3L Colorectal cancer (CRC)
  • 1L Endometrial carcinoma
  • 1L Gastric or gastroesophageal cancer (GC/GEJ)
  • 2L Gastric or gastroesophageal cancer (GC/GEJ)
  • 1L Biliary tract cancer (BTC)

Key Exclusion Criteria for all parts

• Has malignancies other than disease under study within the past 3 years
• Has conditions requiring treatment with clinically significant or increasing doses of systemic steroid therapy
• Has not adequately recovered from recent major surgery
• Has ongoing clinically significant toxicity related to prior therapy
• Has active central nervous system (CNS) metastases
• Has active autoimmune disease requiring systemic therapy in the past 2 years (replacement therapy is permitted)
• Has a history of serious Grade ≥ 3 immune-related adverse event (irAE)
• Has a history of noninfectious pneumonitis/interstitial lung disease
• Has an active severe infection
• Has received a live or attenuated vaccine within 30 days of the first dose
• Has undergone prior allogeneic stem cell or solid organ transplantation
• Has protocol-specified events related to gastrointestinal perforation, surgery, wound healing complications, and bleeding
• Has clinically significant cardiovascular disease

Key Exclusion Criteria for dose expansion only

• Has received prior anti-PD-1/L1 treatment
• Has history of hypersensitivity reaction to the cohort-specific combination agent(s) or its excipients
• Has any contraindication to the cohort-specific combination agent(s)
• Has Grade >1 neuropathy at Screening NOTE: Other protocol defined Inclusion and Exclusion criteria may apply.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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540 participants in 11 patient groups

CR-001 Dose escalation

Experimental group

Description:

Escalating dose levels of CR-001 to define the maximum tolerated dose of CR-001 in participants with locally advanced or metastatic solid tumors who are refractory to or unable to tolerate standard of care treatment, or for whom standard of care treatment is unavailable

Treatment:

Drug: CR-001

CR-001 Backfill

Experimental group

Description:

Escalating dose levels of CR-001 Indication-specific cohort populations will be tested

Treatment:

Drug: CR-001

CR-001 Dose Expansion 3A: First-line (1L) Non-small cell lung cancer

Experimental group

Description:

CR-001 in combination with paclitaxel or pemetrexed + carboplatin

Treatment:

Drug: Carboplatin

Drug: CR-001

Drug: Pemetrexed

Drug: Paclitaxel

CR-001 Dose Expansion 3B: First-line (1L) colorectal cancer

Experimental group

Description:

CR-001 in combination with FOLFOX

Treatment:

Drug: CR-001

Drug: FOLFOX

CR-001 Dose Expansion 3C: Third-line (3L) colorectal cancer

Experimental group

Description:

CR-001 in combination with trifluridine + tipiracil

Treatment:

Drug: CR-001

Drug: trifluridine and tipiracil

CR-001 Dose Expansion 3D: First-line (1L) endometrial carcinoma

Experimental group

Description:

CR-001 in combination with paclitaxel + carboplatin

Treatment:

Drug: Carboplatin

Drug: CR-001

Drug: Paclitaxel

CR-001 Dose Expansion 3E: First-line (1L) gastric/gastroesophageal cancer

Experimental group

Description:

CR-001 in combination capecitabine + oxaliplatin

Treatment:

Drug: Capecitabine

Drug: CR-001

Drug: Oxaliplatin

CR-001 Dose Expansion 3F: Second-line (2L) gastric/gastroesophageal cancer

Experimental group

Description:

CR-001 in combination with paclitaxel

Treatment:

Drug: CR-001

Drug: Paclitaxel

CR-001 Dose Expansion 3G: First-line (1L) Biliary tract cancer

Experimental group

Description:

CR-001 in combination with gemcitabine + cisplatin

Treatment:

Drug: Gemcitabin

Drug: CR-001

Drug: Cisplatin

CR-001 Dose Optimization Cohort X

Experimental group

Description:

monotherapy dose level (DL)-X Indication-specific cohort populations will be tested

Treatment:

Drug: CR-001

CR-001 Dose Optimization Cohort Y

Experimental group

Description:

monotherapy dose level (DL)-Y Indication-specific cohort populations will be tested

Treatment:

Drug: CR-001