Phase I/II study of ANV600 single agent or in combination with pembrolizumab in participants with advanced solid tumors (EXPAND-1)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Anaveon AG

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

6 Aug 2024 → ongoing

Decision date (initial)

2024-07-22

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Anaveon AG

External identifiers

EU CT number

2023-509633-39-00

WHO UTN

U1111-1303-6136

ClinicalTrials.gov

NCT06470763

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Pharmacokinetic

Phase I (dose escalation): To identify the maximum tolerated dose (MTD) and/or recommended Phase II dose (RP2D) of ANV600 single agent and in combination with pembrolizumab.

Phase II: To assess the anti-tumor activity of ANV600 as single agent and in combination with pembrolizumab.

Secondary objectives 7

1. Phase I: To characterize the pharmacokinetics (PK) of ANV600 single agent and in combination with pembrolizumab after single dose and repeated dosing.
2. Phase I: To evaluate the prevalence and incidence of immunogenicity of ANV600.
3. Phase I: To describe the anti-tumor activity of ANV600 as single agent and in combination with pembrolizumab.
4. Phase II: To assess the anti-tumor activity of ANV600 as single agent and in combination with pembrolizumab.
5. Phase II: To assess the safety and tolerability ANV600 single agent and in combination with pembrolizumab for each cohort and in the overall study population.
6. Phase II: To characterize the PK of ANV600 single agent and in combination with pembrolizumab after single dose and repeated dosing.
7. Phase II: To evaluate the prevalence and incidence of immunogenicity of ANV600.

Conditions and MedDRA coding

Advanced solid tumours

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. 1. The participant (or legally acceptable representative if applicable) provides written informed consent for the trial;
2. 2. Life-expectancy ≥ 3 months;
3. 3. Must be able to comply with the Protocol as judged by the Investigator;
4. 4. Be ≥ 18 years of age on day of signing informed consent;
5. 5. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1;
6. 6. Have measurable disease per RECIST v1.1 as assessed by the local site investigator/radiology. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions;
7. 7. Phase I : Participants with advanced unresectable or metastatic solid tumors for which no standard of care treatments are available, or participants who cannot tolerate such treatment. Phase II: Additional cohort specific criteria apply;
8. 8. Have adequate organ function as defined in the protocol;
9. 9. Negative serum pregnancy test within 7 days prior to the first dose of study treatment in women of childbearing potential and women <12 months after menopause;
10. 10. Female participants who are not postmenopausal, and who have not undergone surgical sterilization, must agree to use highly effective methods of contraception during the treatment period and for 6 months after the last dose of study treatment. They must also agree not to donate eggs (ova, oocytes) during the same timeframe;
11. 11. Male participants with partners of childbearing potential must agree to use highly effective methods of contraception and barrier contraception (condom) during the treatment period and for 6 months after the last dose of study treatment. They must also agree not to donate sperm during the same timeframe.

Exclusion criteria 25

1. 1. For Phase I: Participants with pancreatic cancer (e.g. PDAC) or primary or secondary adrenal insufficiency;
2. 10. Have a known additional malignancy that is progressing or has required active treatment within the past 3 years;
3. 11. Have received prior radiotherapy within 2 weeks of start of study treatment or have had a history of radiation pneumonitis;
4. 12. Active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment and is allowed;
5. 13. Have a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study drug;
6. 14. Have had an allogeneic tissue/solid organ or stem cell transplant;
7. 15. Have a history of (non-infectious) pneumonitis / interstitial lung disease that required steroids or has current pneumonitis / interstitial lung disease;
8. 16. Have an active infection requiring systemic therapy;
9. 17. Are known to be human immunodeficiency virus (HIV) positive (or tests positive for HIV 1 or 2 at Screening), unless the following criteria are met: • CD4+ lymphocyte count >350 cells/µL; • Had no history of acquired immunodeficiency syndrome (AIDS)-defining opportunistic infections within the past 12 months; • Have been on established anti-retroviral therapy for at least 4 weeks; and • Have an HIV viral load of <50 copies/mL prior to study Day 1.
10. 18. Have uncontrolled hepatitis B infection or hepatitis C infection;
11. 19. Have a history of an acute coronary event (e.g., myocardial infarction) within 3 months prior to study Day 1, uncontrolled and symptomatic coronary artery disease, or congestive heart failure NYHA Class III/IV;
12. 2. For Phase II: Participants with uveal and mucosal melanoma, and participants with primary tumor site of nasopharynx;
13. 20. Have an average QTcF interval >470 msec at screening;
14. 21. Have received a live vaccine, live-attenuated vaccine, mRNA-Based or Virus-Vectored vaccines within 30 days of study Day 1;
15. 22. Have a known psychiatric or substance abuse disorder that would interfere with the participant’s ability to cooperate with the requirements of the study;
16. 23. Have a history or current evidence of any condition, therapy, or laboratory abnormality, or other circumstance that might confound the results of the study or interfere with the participant's participation for the full duration of the study, such that it is not in the best interest of the participant to participate, in the opinion of the treating investigator;
17. 24. Are pregnant, breastfeeding or expecting to conceive or father children during the study, from the screening visit through 6 months after the last dose of study treatment.
18. 3. History of allergic reactions attributed to any of the excipients of ANV600, such as sucrose, histidine or polysorbate 80. For combination only: Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients;
19. 4. Have received investigational agent (including investigational device) within 4 weeks or an interval of five half-lives of the respective investigational agent prior to study Day 1; whichever is shorter;
20. 5. Have received IL-2 or IL-2 analogues as anti-cancer therapy within 18 months prior to study Day 1 (except IL-2 given in combination with cell therapy [e.g. TILs]);
21. 6. Have not recovered (i.e., ≤ Grade 1 at baseline) from AEs resulting from prior immunotherapies with the following exceptions: a. Autoimmune AEs controlled by replacement therapy (e.g., hypothyroidism, adrenal insufficiency) b. Vitiligo or alopecia c. Psoriasis;
22. 7. Have received prior systemic anti-cancer therapy including investigational agents within 4 weeks (could consider shorter interval for kinase inhibitors or other short half-life drugs) prior to treatment;
23. 8. For combination only: Have received prior immunotherapy, and was discontinued from that treatment due to a Grade 3 or higher irAE (except endocrine disorders that can be treated with replacement therapy) or was discontinued from that treatment due to Grade 2 myocarditis or recurrent Grade 2 pneumonitis;
24. 9. Have known active central nervous system metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, i.e., without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study treatment;
25. 25. Are deprived of liberty by judicial or administrative decision and/or subject to a legal protection measure (curatorship, safeguard of justice).

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 4

1. Phase I: Incidence of dose limiting toxicities (DLT) with ANV600 single agent and in combination with pembrolizumab.
2. Phase I: Frequency and severity of treatment-emergent adverse events (TEAEs) with ANV600 and in combination with pembrolizumab.
3. Phase II: Objective response rate (ORR) using RECIST v1.1.
4. Phase II: Duration of response (DOR) using RECIST v1.1.

Secondary endpoints 9

1. Phase I: PK parameters based on ANV600 serum levels following a single dose and after repeated dosing.
2. Phase I: Immunogenicity as indicated by the incidence of anti-drug antibodies (ADA) and neutralizing antibodies (nAb).
3. Phase I: ORR using RECIST v1.1.
4. Phase I: DOR using RECIST v1.1.
5. Phase II: Progression-free Survival (PFS).
6. Phase II: Overall survival (OS).
7. Phase II: Frequency and severity of TEAEs with ANV600 and in combination with pembrolizumab.
8. Phase II: PK parameters based on ANV600 serum levels following a single dose and after repeated dosing.
9. Phase II: Immunogenicity as indicated by the incidence of ADA and nAb.

Investigational products

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

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Anaveon AG

Sponsor organisation

Anaveon AG

Address

Hochbergerstrasse 60c

City

Basel

Postcode

4057

Country

Switzerland

Scientific contact point

Organisation

Anaveon AG

Contact name

Anaveon

Public contact point

Organisation

Anaveon AG

Contact name

Medpace Finland Oy

Third parties 8

Locations

5 EU/EEA countries · 18 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

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

Documents 48 files

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

Application history

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