A Phase 1b-2 Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy of LRK-4189 Alone and in Combination in Patients with Solid Tumors

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Larkspur Biosciences Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Decision date (initial)

2026-07-03

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Larkspur Biosciences, Inc.

External identifiers

EU CT number

2026-525629-20-00

ClinicalTrials.gov

NCT07498725

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Pharmacodynamic, Efficacy, Pharmacokinetic

Identify an appropriate dose of LRK-4189 for initial expansion (active dose or maximum tolerated dose [MTD]), evaluate the preliminary efficacy of LRK-4189 in patients with metastatic colorectal cancer (mCRC) and determine the optimal dose of LRK-4189 in specific indications

Secondary objectives 4

1. Determine the PK of LRK-4189
2. Further document safety and tolerability of LRK-4189
3. Document the safety, tolerability, PK and preliminary efficacy of LRK-4189 in combination with mFOLFOX6 or FOLFIRI
4. Evaluate the mechanism of action through the PD of LRK-4189

Conditions and MedDRA coding

Solid tumors

Regulatory references

Scientific advice from competent authorities

Swedish Medical Products Agency, Medicines And Healthcare Products Regulatory Agency

Plan to share IPD

No

IPD plan description

We are undecided at this stage

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 13

1. Able and willing to sign the informed consent form and consent with the protocol and the restrictions and assessments therein
2. ≥18 years of age
3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
4. Must have a histologically proven locally advanced or metastatic inoperable tumor that has progressed on/after at least one line of prior therapy considered standard of care in the advanced/metastatic setting
5. In the investigator’s opinion, the patient may not derive clinical benefit from, or is ineligible for, a particular form of standard therapy on medical grounds, or the patient failed or did not tolerate one or more other anti-cancer therapies
6. RECIST 1.1 evaluable disease
7. Provide a sufficient and adequate formalin-fixed paraffin-embedded (FFPE) tumor tissue sample (biopsy) collected after the last dose of prior systemic anti-cancer therapy and before the first dose of study treatment from a site not previously irradiated
8. Agree to mandatory on-treatment biopsy (if clinically feasible at time of biopsy).
9. QT interval corrected using the Fridericia method (QTcf) ≤ 480 msec
10. Evidence of adequate organ function at screening
11. All previous anti-cancer therapy-related AEs (including peripheral neuropathy) should have resolved to Grade 1 or baseline value with the exception of alopecia and stable, treated endocrine toxicities of immune checkpoint inhibitors
12. Female patients must be of non-child-bearing potential or if of child-bearing potential, must agree not to attempt to become pregnant, must not donate ova, and, if engaging in sexual intercourse with a male partner, must agree to use a highly effective method(s) of contraception from signing the consent form until at least 6 months after the last dose of study drug (9 months if receiving oxaliplatin)
13. Male patients must agree not to donate sperm and if engaging in sexual intercourse with a female partner who could become pregnant, must agree to use a condom and their partner must be advised to also use a highly effective method of contraception from signing the consent form until at least 6 months after the last dose of study drug (9 months if receiving oxaliplatin)

Exclusion criteria 17

1. Unable due to concomitant treatment or variant anatomy to swallow or absorb LRK-4189 as an oral formulation
2. Known hypersensitivity to LRK-4189 or any of its excipients
3. Contraindication to serial biopsies
4. Symptomatic ascites or pleural effusion requiring therapeutic thoraco- or paracentesis in the 6 weeks before treatment.
5. Known active central nervous system metastases and/or carcinomatous meningitis; brain metastases requiring treatment with steroids
6. For expansion phase only: presence of any other active malignancy requiring systemic therapy other than the disease under study
7. Concurrent anti-cancer therapy
8. Known active infection with human immunodeficiency virus, hepatitis B or hepatitis C, defined by a detectable viral load. Note: testing is not required for eligibility
9. Use of systemic corticosteroids to treat inflammatory or autoimmune symptoms within 2 weeks or other immunosuppressive drugs within 30 days prior to the start of the study
10. Active infection requiring IV therapy. If receiving systemic oral antibiotics, patients must be afebrile for at least 3 days prior to dosing to be eligible
11. Participants taking medications that are strong XXXX or XXXX or XXX that cannot be discontinued at least 14 days prior to initiating study treatment
12. Therapeutic anticoagulation if it cannot be withheld to enable biopsies to be performed safely.
13. History or clinical evidence of any surgical or medical condition which the Investigator or Medical Monitor judges as likely to interfere with the results of the study, poses an additional risk in participating, or makes the patient unlikely to comply with the study related visits and assessments, particularly any pre-existing condition that would put the patient at additional risk
14. Unable to comply with the visits and requirements of the protocol due to psychiatric condition or substance abuse
15. Pregnant or breastfeeding or planning to conceive or father children within the projected duration of the study and subsequent 3 months
16. Combination cohorts: contraindication to receive mFOLFOX6 or FOLFIRI, whichever is applicable
17. Patients receiving capecitabine or fluorouracil: known history or positive test for DPD deficiency.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. Part 1: Incidence, type and severity of adverse events (AEs) and serious AEs (SAEs), dose-limiting toxicity (DLT), treatment interruptions and discontinuations, by grade and attribution, safety labs and test results  PK parameters as below  If feasible, PD parameters as below  Shrinkage of target lesions
2. Part 2 : Per Response Evaluation Criteria in Solid Tumors (RECIST 1.1) [Eisenhauer 2009]: Objective response rate (ORR); Disease control rate (DCR), comprising ORR + stable disease (SD) (on at least 2 post-baseline timepoints > 4 weeks apart); Duration of response (DOR); Progression-free survival (PFS); Overall survival (OS)
3. Part 3: Safety parameters as for Part 1; Efficacy parameters as for Part 2; PK parameters as for secondary endpoints; PD parameters as for exploratory endpoints

Secondary endpoints 4

1. All that can be determined of: Time to maximum concentration (tmax);Terminal half-life (t½); Maximum observed concentration (Cmax);Area under the concentApparent volume of distribution at steady state (Vss/F);Mean residence time (MRT)ration-time curve from time zero to 24 hours and last detectable concentration (AUC0-24, AUClast); Area under the concentration-time curve from time zero extrapolated to infinity (AUC∞);Apparent total clearance (CL/F);Terminal elimination rate constant (λz);Appa
2. Safety parameters as Part 1
3. Safety parameters as Part 1;Efficacy parameters as Part 2;PK parameters as above
4. PD measurements in blood and/or tumor tissue for some or all of: Peripheral blood mononuclear cells (PBMCs): target degradation; PBMCs: immune cell frequency; PBMCs: activation state; Circulating tumor DNA (ctDNA); Bulk or single cell RNAseq or other nucleic acid testing; Whole exome sequencing of tumor; Serum for secreted protein (cytokine, chemokine) analysis ;Immunohistochemistry (IHC) for tumor and immune markers of PD including target degradation.

Investigational products

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

Test 1

Auxiliary 6

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Larkspur Biosciences Inc.

Sponsor organisation

Larkspur Biosciences Inc.

Address

1 Canal Park Suite 210

City

Cambridge

Postcode

02141-2234

Country

United States

Scientific contact point

Organisation

Larkspur Biosciences Inc.

Contact name

Krista Goodman

Public contact point

Organisation

Larkspur Biosciences Inc.

Contact name

Sujen Lai

Third parties 10

Locations

1 EU/EEA country · 3 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 22 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