A Study of CM24 in Combination With Nivolumab in Adults With Advanced Solid Tumors

Ovarian Cancer Clinical Trial

Official title:

A Phase 1/2 Study to Assess the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Efficacy of CM24 in Combination With Nivolumab in Adults With Advanced Solid Tumors

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04731467
• Other study ID #: FW-2020-1
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: March 19, 2021
• Est. completion date: January 2025

Study information

• Verified date: April 2024
• Source: Purple Biotech Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is an open-label, multicenter, multi-dose escalation and dose expansion study in subjects with selected advanced solid tumors (Part A) and advanced metastatic pancreatic cancer (Parts C & D) to evaluate the safety and tolerability of CM-24 in combination with nivolumab. In Part C of the study gemcitabine/nab-paclitaxel or Nal-IRI/5-FU/LV will be administered subsequent to CM24 and nivolumab. CM24, nivolumab and gemcitabine/nab-paclitaxel or Nal-IRI/5-FU/LV are administered intravenously.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 79
• Est. completion date: January 2025
• Est. primary completion date: December 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Part A: Previously treated subjects with recurrent and/or metastatic NSCLC, pancreatic cancer, ovarian cancer, papillary thyroid cancer, colorectal adenocarcinoma and melanoma with documented progression/intolerance following at least one previous therapy (and not more than 2 previous regimens); Part C: Subjects with histologically confirmed advanced metastatic pancreatic adenocarcinoma as defined by NCCN Guidelines; Subjects with islet cell neoplasms are excluded; subjects with a maximum of 1 prior treatment regimen for metastatic disease excluding: nab-paclitaxel containing regimens and up to 8 weeks from last chemotherapy treatment (Arm #1); fluoropyrimidine or irinotecan containing regimens and up to 8 weeks from last chemotherapy treatment (Arm #2). Part C, D: Subjects with histologically confirmed advanced metastatic pancreatic adenocarcinoma as defined by NCCN Guidelines; Subjects with islet cell neoplasms are excluded.

2. Parts C, D: Subjects who have progressed on or after standard of care chemotherapy

with a maximum of 1 prior treatment regimen for advanced metastatic disease:

• Subjects enrolled in arm with gemcitabine/nab-paclitaxel combination should have received a fluoropyrimidine and/or irinotecan containing regimen in the first line of treatment; Prior gemcitabine containing regimen may be allowed only if completed at least 6 months prior to study enrollment.
• Arm #2: Subjects enrolled in arm with Nal-IRI/5FU/LV combination should have received a gemcitabine and/or nab-paclitaxel containing regimen in the first line of treatment; Prior irinotecan and/or fluoropyrimidine containing regimens may be allowed only if completed at least 6 months prior to study enrollment.

3. Part A: Availability of an archival tumor sample prior to first treatment. Parts C, D:

Fresh tumor biopsy must be obtained within 3 months prior to enrollment and after the last systemic treatment was completed.

4. Must have at least 1 measurable lesion per RECIST1.1 with progressing or new tumors since last antitumor therapy;

5. ECOG performance status score of 0 or 1;

6. Adequate safety lab results;

7. Stable brain metastases;

8. WCBP (Women of Childbearing Potential) must have a negative serum pregnancy test at Screening and a negative urine pregnancy test, WCBP must agree to abstain from sex or use an adequate method of contraception, males must abstain from sex with WCBP or use an adequate method of contraception.

Exclusion Criteria:

1. Part A: Received more than two prior systemic regimens for the metastatic disease Parts C and D: Received more than 1 prior systemic regimens for the advanced metastatic disease

2. Part A: History of weight loss >10% over the 2 months prior to Screening;

3. Unresolved AEs > Grade 1 from prior anticancer therapy.

4. Concurrent malignancy requiring treatment;

5. Active, untreated central nervous system (CNS) metastases;

6. Subjects previously treated with an anti PD-1/PD-L1 targeting agent with history immune mediated toxicity;

7. Severely immunocompromised;

8. History of allergy or hypersensitivity to any of the study treatment components;

9. Major surgery within 4 weeks of study administration;

10. Received a live / attenuated vaccine within 30 days of first treatment

11. Clinically relevant serious co-morbid medical conditions including, but not limited

to:

• Active infection;
• Recent (within six months of Screening) cardiac disease, myocardial infarction, or severe or unstable angina;
• History of serious arrhythmia;
• Chronic obstructive or chronic restrictive pulmonary disease, pulmonary hypertension history of or active interstitial lung disease or pneumonitis;
• Prior organ allograft;
• Subjects with active, known or suspected autoimmune disease;
• History of active or latent tuberculosis infection;
• Positive test for HIV, HBV, or HCV;

12. Radiation within two weeks prior to the first study treatment;

13. Treatment with another investigational therapy within 30 days or 5 half-lives of the drug prior to Screening, whichever is longer;

14. Treatment with botanical preparations (e.g., herbal supplements or traditional Chinese medicines) intended for general health support or to treat the disease under study within 2 weeks prior to treatment;

15. Pregnant or lactating women.

Related Conditions & MeSH terms

• Colorectal Adenocarcinoma
• Melanoma
• Non Small Cell Lung Cancer
• Ovarian Cancer
• Pancreatic Cancer
• Papillary Thyroid Cancer
• Solid Tumor
• Thyroid Cancer, Papillary

Intervention

Drug:
• CM-24 and Nivolumab - Dose Escalation
Dose escalation of CM24 with nivolumab in adult patients with selected recurrent or metastatic solid tumors
• CM-24, Nivolumab, Nab paclitaxel and Gemcitabine - Expansion
Expansion cohort of CM24 in combination with nivolumab, nab-paclitaxel and gemcitabine in adult patients with advanced metastatic pancreatic cancer
• CM-24, Nivolumab, and Nal-IRI/5-FU/LV - Expansion
Expansion cohort of CM24 in combination with nivolumab and Nal-IRI/5-FU/LV in adult patients with advanced metastatic pancreatic cancer
• Nivolumab, Nab paclitaxel and Gemcitabine - Expansion
Expansion cohort of nivolumab in combination with nab-paclitaxel and gemcitabine in adult patients with advanced metastatic pancreatic cancer
• Nivolumab and Nal-IRI/5-FU/LV - Expansion
Expansion cohort of nivolumab in combination with Nal-IRI/5-FU/LV in adult patients with advanced metastatic pancreatic cancer

Locations

Country	Name	City	State
Israel	Rambam Health Care Campus	Haifa
Israel	Sheba Medical Center	Ramat Gan
Spain	Hospital Clinic Barcelona	Barcelona
Spain	NEXT Oncology Barcelona	Barcelona
Spain	Vall d' Hebron Institute of Oncology (VHIO)	Barcelona
Spain	Clinica Universidad de Navarra	Madrid
Spain	Hospital 12 Octubre	Madrid
Spain	Hospital General Universitario Gregorio Maranon	Madrid
Spain	Hospital South Texas Accelerated Research Therapeutics (START) Madrid - CIOCC	Madrid
Spain	South Texas Accelerated Research Therapeutics (START) Madrid - Hospital Fundacion Jimenez Diaz	Madrid
Spain	Clinica Universidad de Navarra - Pamplona	Pamplona
Spain	NEXT Oncology Madrid	Pozuelo de Alarcon
Spain	Hospital Quiron Salud Valencia	Valencia
United States	University of Colorado	Aurora	Colorado
United States	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan
United States	The University of Texas M.D. Anderson Cancer Center	Houston	Texas
United States	Yale University	New Haven	Connecticut
United States	HonorHealth Research Institute	Scottsdale	Arizona

Sponsors (2)

Lead Sponsor	Collaborator
Famewave Ltd.	Bristol-Myers Squibb

Countries where clinical trial is conducted

United States,  Israel,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Part A: Incidence of treatment emergent adverse events	Incidence of treatment emergent adverse events with CM-24 and nivolumab in adults with selected recurrent or metastatic solid tumors	Up to 24 months
Primary	Part C: Safety and tolerability	Incidence of treatment emergent adverse events with CM-24 is used in combination with nivolumab and gemcitabin/nab-paclitaxel or Nal-IRI/5-FU/LV in adults with advanced metastatic pancreatic cancer	Up to 24 months
Primary	Part D: Overall survival	This is an exploratory randomized sub-study with the objective of estimating the efficacy of CM24 and nivolumab with chemotherapy (Nal-IRI/5-FU/LV or gemcitabine/ nab-paclitaxel) and chemotherapy only (Nal- IRI/5-FU/LV or gemcitabine/nab-paclitaxel) as measured by overall survival.	Up to 24 months
Secondary	Maximum serum concentration [Cmax]	Maximum serum concentration [Cmax] of CM24	Up to 24 months
Secondary	Time of maximum concentration [Tmax]	Time of maximum concentration [Tmax] of CM24	Up to 24 months
Secondary	Area under the serum concentration curve [AUC]	Area under the serum concentration curve [AUC] of CM24	Up to 24 months
Secondary	Half life	Half life of CM24	Up to 24 months
Secondary	Drug clearance	Drug clearance of CM24	Up to 24 months
Secondary	Volume of distribution	Volume of distribution of CM24	Up to 24 months
Secondary	Serum ADA parameters	Serum ADA parameters of CM24 as measured by percentage of patients who are positive for the presence of anti-drug antibodies	Up to 24 months
Secondary	Objective Response Rate when CM24 is used in combination with nivolumab		Up to 24 months
Secondary	Disease Control Rate when CM24 is used in combination with nivolumab		Up to 24 months
Secondary	Median Duration of Response when CM24 is used in combination with nivolumab		Up to 24 months
Secondary	Median Time to Response when CM24 is used in combination with nivolumab		Up to 24 months
Secondary	Progression Free Survival when CM24 is used in combination with nivolumab		Up to 48 months
Secondary	Overall Survival when CM24 is used in combination with nivolumab		Up to 48 months
Secondary	Population pharmacokinetics when CM24 is used in combination with nivolumab as measured by the maximum plasma concentration [Cmax]		Up to 24 months
Secondary	Population pharmacokinetics when CM24 is used in combination with nivolumab as measured by the average area under the concentration curve [AUC]		Up to 24 months
Secondary	Population pharmacokinetics when CM24 is used in combination with nivolumab as measured by the median area under the concentration curve [AUC]		Up to 24 months
Secondary	Population pharmacokinetics when CM24 is used in combination with nivolumab and gemcitabin/nab-paclitaxel or Nal-IRI/5-FU/LV as measured by the maximum plasma concentration [Cmax]		Up to 24 months
Secondary	Population pharmacokinetics when CM24 is used in combination with nivolumab and gemcitabin/nab-paclitaxel or Nal-IRI/5-FU/LV as measured by the average area under the concentration curve [AUC]		Up to 24 months
Secondary	Population pharmacokinetics when CM24 is used in combination with nivolumab and gemcitabin/nab-paclitaxel or Nal-IRI/5-FU/LV as measured by the median area under the concentration curve [AUC]		Up to 24 months
Secondary	Disease Control Rate when CM24 is used in combination with nivolumab and gemcitabin/nab-paclitaxel or Nal-IRI/5-FU/LV		Up to 24 months
Secondary	Duration of Response when CM24 is used in combination with nivolumab and gemcitabin/nab-paclitaxel or Nal-IRI/5-FU/LV		Up to 24 months
Secondary	Time to Response when CM24 is used in combination with nivolumab and gemcitabin/nab-paclitaxel or Nal-IRI/5-FU/LV		Up to 24 months
Secondary	Progression Free Survival when CM24 is used in combination with nivolumab and gemcitabin/nab-paclitaxel or Nal-IRI/5-FU/LV		Up to 48 months
Secondary	Overall Survival when CM24 is used in combination with nivolumab and gemcitabin/nab-paclitaxel or Nal-IRI/5-FU/LV		Up to 48 months