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

Phase 1

Completed

• Conditions: Ovarian Cancer; Solid Tumor; Melanoma; Non Small Cell Lung Cancer; Pancreatic Cancer; Papillary Thyroid Cancer; Colorectal Adenocarcinoma
• Interventions: Drug: Nivolumab and Nal-IRI/5-FU/LV - Expansion; Drug: CM-24, Nivolumab, and Nal-IRI/5-FU/LV - Expansion; Drug: CM-24, Nivolumab, Nab paclitaxel and Gemcitabine - Expansion; Drug: Nivolumab, Nab paclitaxel and Gemcitabine - Expansion; Drug: CM-24 and Nivolumab - Dose Escalation

• Registration Number: NCT04731467
• Lead Sponsor: Famewave Ltd.

Brief 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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2021-01-24
• Study First Submitted QC: 2021-01-28
• Study First Posted: 2021-02-01
• Study Start: 2021-03-19
• Status Verified: 2024-06
• Primary Completion: 2024-09-30
• Study Completion: 2024-09-30
• Last Update Submitted: 2024-12-23
• Last Update Posted: 2024-12-27

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 79

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Part D- Expansion cohort of nivolumab in combination with Nal-IRI/5-FU/LV	Nivolumab and Nal-IRI/5-FU/LV - Expansion	-
Part C- Expansion cohort of CM24 in combination with nivolumab and Nal-IRI/5-FU/LV	CM-24, Nivolumab, and Nal-IRI/5-FU/LV - Expansion	-
Part D- Expansion cohort of CM24 in combination with nivolumab, nab-paclitaxel and gemcitabine	CM-24, Nivolumab, Nab paclitaxel and Gemcitabine - Expansion	-
Part D- Expansion cohort of nivolumab in combination with nab-paclitaxel and gemcitabine	Nivolumab, Nab paclitaxel and Gemcitabine - Expansion	-
Part C- Expansion cohort of CM24 in combination with nivolumab, nab-paclitaxel and gemcitabine	CM-24, Nivolumab, Nab paclitaxel and Gemcitabine - Expansion	-
Part A- Dose escalation of CM24 in combination with nivolumab	CM-24 and Nivolumab - Dose Escalation	-
Part D- Expansion cohort of CM24 in combination with nivolumab and Nal-IRI/5-FU/LV	CM-24, Nivolumab, and Nal-IRI/5-FU/LV - Expansion	-

Primary Outcome Measures

Name	Time	Method
Part A: Incidence of treatment emergent adverse events	Up to 24 months	Incidence of treatment emergent adverse events with CM-24 and nivolumab in adults with selected recurrent or metastatic solid tumors
Part D: Overall survival	Up to 24 months	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.
Part C: Safety and tolerability	Up to 24 months	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

Secondary Outcome Measures

Name	Time	Method
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
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
Disease Control Rate when CM24 is used in combination with nivolumab	Up to 24 months
Overall Survival when CM24 is used in combination with nivolumab	Up to 48 months
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
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
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
Median Duration of Response when CM24 is used in combination with nivolumab	Up to 24 months
Median Time to Response when CM24 is used in combination with nivolumab	Up to 24 months
Area under the serum concentration curve [AUC]	Up to 24 months	Area under the serum concentration curve \[AUC\] of CM24
Drug clearance	Up to 24 months	Drug clearance of CM24
Progression Free Survival when CM24 is used in combination with nivolumab	Up to 48 months
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
Half life	Up to 24 months	Half life of CM24
Serum ADA parameters	Up to 24 months	Serum ADA parameters of CM24 as measured by percentage of patients who are positive for the presence of anti-drug antibodies
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
Maximum serum concentration [Cmax]	Up to 24 months	Maximum serum concentration \[Cmax\] of CM24
Time of maximum concentration [Tmax]	Up to 24 months	Time of maximum concentration \[Tmax\] of CM24
Volume of distribution	Up to 24 months	Volume of distribution of CM24
Objective Response Rate when CM24 is used in combination with nivolumab	Up to 24 months
Population pharmacokinetics when CM24 is used in combination with nivolumab as measured by the maximum plasma concentration [Cmax]	Up to 24 months
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
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
Overall Survival when CM24 is used in combination with nivolumab and gemcitabin/nab-paclitaxel or Nal-IRI/5-FU/LV	Up to 48 months

Trial Locations

Locations (18)

University of Colorado; 🇺🇸 Aurora, Colorado, United States

Barbara Ann Karmanos Cancer Institute; 🇺🇸 Detroit, Michigan, United States

Yale University; 🇺🇸 New Haven, Connecticut, United States

Rambam Health Care Campus; 🇮🇱 Haifa, Israel

HonorHealth Research Institute; 🇺🇸 Scottsdale, Arizona, United States

The University of Texas M.D. Anderson Cancer Center; 🇺🇸 Houston, Texas, United States

Sheba Medical Center; 🇮🇱 Ramat Gan, Israel

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

South Texas Accelerated Research Therapeutics (START) Madrid - Hospital Fundacion Jimenez Diaz; 🇪🇸 Madrid, Spain

NEXT Oncology Madrid; 🇪🇸 Pozuelo de Alarcon, Spain

Hospital Quiron Salud Valencia; 🇪🇸 Valencia, Spain

Clinica Universidad de Navarra - Pamplona; 🇪🇸 Pamplona, Spain

Hospital 12 Octubre; 🇪🇸 Madrid, Spain

Hospital General Universitario Gregorio Maranon; 🇪🇸 Madrid, Spain

Hospital South Texas Accelerated Research Therapeutics (START) Madrid - CIOCC; 🇪🇸 Madrid, Spain